Summary of Lecture 2: Atoms, Molecules, and Water (Bio93, Dr. Jorge Busciglio)

1. Key Concepts and Nomenclature:

• Atoms are the smallest units of chemical elements, made up of protons, neutrons, and electrons.

• Molecules are two or more atoms bonded together.

• Compounds are molecules made from two or more different elements in a fixed ratio.

• Chemical bonds:

  • Covalent bonds involve the sharing of electrons between atoms.

  • Ionic bonds involve the transfer of electrons between atoms.

  • Hydrogen bonds are weak interactions where a hydrogen atom covalently bonded to one atom forms a second, weaker bond with an electronegative atom of another molecule.

2. Importance of Water in Biology:

• Water is crucial for life, making up 70-95% of the cell's composition.

• It has special properties due to its molecular structure, where oxygen (O) is covalently bonded to two hydrogen (H) atoms, forming polar bonds.

  • Polar Covalent Bonds: Oxygen has a partial negative charge and hydrogen has a partial positive charge, giving water its polar nature.

  • Cohesion: Water molecules form hydrogen bonds with each other, allowing for processes like water transport in plants (capillary action).

  • Solvent Properties: Water is an excellent solvent due to its polarity, allowing it to dissolve various substances (e.g., NaCl) and form hydration shells around ions.

3. Types of Chemical Bonds:

• Covalent Bonds: Electrons are shared between atoms.

  • Nonpolar covalent bonds: Electrons are shared equally.

  • Polar covalent bonds: Electrons are shared unequally, leading to partial charges (e.g., in water).

• Ionic Bonds: Electrons are transferred from one atom to another (e.g., NaCl).

• Hydrogen Bonds: Weak interactions between a hydrogen atom in one molecule and an electronegative atom in another (e.g., between water molecules).

4. Properties of Water:

• Cohesion: Water molecules are attracted to each other, helping water move up through plant vessels.

• Solvent: Water dissolves a wide range of substances, including ionic and polar molecules, forming hydration shells around ions.

• Hydrophilic vs. Hydrophobic:

  • Hydrophilic substances are attracted to water and can form hydrogen bonds (e.g., NaCl, proteins with polar or ionic regions).

  • Hydrophobic substances repel water and tend to have nonpolar bonds (e.g., lipids).

5. pH and Water Dissociation:

• Water dissociation: Water can dissociate into a hydrogen ion (H⁺) and a hydroxide ion (OH⁻). In pure water, concentrations of H⁺ and OH⁻ are equal.

  • Acids increase the H⁺ concentration (e.g., HCl dissociates into H⁺ and Cl⁻).

  • Bases decrease the H⁺ concentration (e.g., NH₃ accepts H⁺, or NaOH dissociates into Na⁺ and OH⁻).

• pH Scale: Measures the acidity or basicity of a solution. Lower pH means more acidic (higher H⁺ concentration), and higher pH means more basic (lower H⁺ concentration).

6. Buffers and pH Regulation:

• Buffers are systems that help maintain a stable pH in biological systems by either donating H⁺ or accepting OH⁻ as needed.

• Example: The carbonic acid-bicarbonate buffer in human blood maintains a pH of around 7.4, essential for proper enzyme function and cellular activities.

7. Biological Relevance of Water:

• Water's special properties (cohesion, solvent, and its ability to stabilize pH) are vital for cellular processes, biochemical reactions, and maintaining homeostasis in living organisms.

• The structure of water and its ability to form hydrogen bonds allows it to facilitate life-supporting functions like nutrient transport, temperature regulation, and maintaining cellular structure.

8. Learning Outcomes:

• Understand the structural organization of cells, from atoms to molecules to compounds.

• Recognize different types of chemical bonds and their biological importance.

• Grasp the molecular structure and unique properties of water, and its central role in life.

• Be able to calculate pH, understand acid-base reactions, and predict buffer system behavior.

• Summary of Lecture 3: Macromolecules I: Carbon, Carbohydrates, and Lipids

Dr. Jorge Busciglio, Bio93

Key Definitions:

• Carbohydrates: Organic molecules made of carbon, hydrogen, and oxygen. Key types include:

  • Monosaccharides: Simple sugars (e.g., glucose).

  • Disaccharides: Two monosaccharides linked by a glycosidic bond (e.g., lactose, sucrose).

  • Polysaccharides: Long chains of monosaccharides (e.g., starch, glycogen, cellulose).

• Phospholipids: Lipid molecules composed of glycerol, two fatty acids, a phosphate group, and choline. They are essential components of cell membranes, forming bilayers that separate the internal and external environments of cells.

• Lipids: Hydrophobic molecules that include fats, phospholipids, and steroids. Lipids serve in energy storage, insulation, and cell communication.

• Steroids: A class of lipids that have a four-ring carbon skeleton. Cholesterol is the most well-known steroid and serves as a precursor for hormones like testosterone and estrogen.

• Proteins: Macromolecules made of amino acids linked by peptide bonds. Proteins perform a wide range of functions, including catalyzing reactions, providing structural support, and transporting molecules.

• DNA: A nucleic acid that carries genetic information. It consists of two strands of nucleotides wound into a double helix and serves as the blueprint for protein synthesis.

• Chemical/Functional Groups: Specific groups of atoms within molecules that affect the molecule’s reactivity and properties (e.g., hydroxyl groups, amino groups, and carboxyl groups).

• Polymer: A long molecule made up of similar subunits (monomers) connected by covalent bonds (e.g., proteins, nucleic acids, carbohydrates).

Lecture Highlights:

Carbon-Based Molecules:

• Carbon is the foundation of organic molecules, capable of forming stable covalent bonds due to its four valence electrons. This allows it to form diverse structures, including chains, rings, and branching patterns.

• Carbon can bond with various elements such as hydrogen, oxygen, nitrogen, sulfur, and phosphorus to form the basis of key biological macromolecules like carbohydrates, lipids, proteins, and DNA.

Functional Groups:

• Functional groups (e.g., hydroxyl, amino, carboxyl) are specific atom groupings that influence a molecule's behavior in reactions. They play crucial roles in the chemical properties and biological functions of organic molecules.

Carbohydrates:

• Monosaccharides (simple sugars) like glucose are key energy sources for cells. They vary in the location of the carbonyl group and the length of the carbon chain.

• Monosaccharides can combine to form disaccharides (e.g., lactose) and polysaccharides (e.g., starch, glycogen, cellulose), which serve in energy storage and structural roles.

• Lactose intolerance occurs in individuals lacking the enzyme lactase, which is necessary to break down lactose. A genetic mutation allowing the continued production of lactase in adulthood exists in some human populations.

Lipids:

• Lipids are a diverse group of hydrophobic molecules, not classified as polymers. They include fats, phospholipids, and steroids.

  • Fats: Consist of glycerol and fatty acid chains. They can be saturated (no double bonds in fatty acid chains) or unsaturated (contain one or more double bonds).

  • Saturated fats (e.g., butter, lard) are solid at room temperature and are linked to health problems when consumed in excess.

  • Unsaturated fats (e.g., oils, margarine) are typically liquid at room temperature and are considered healthier.

  • Hydrogenated fats are artificially converted to saturated fats by adding hydrogen, often resulting in trans fats. These are linked to cardiovascular diseases by raising LDL ("bad") cholesterol and lowering HDL ("good") cholesterol.

  • Polyunsaturated fats contain multiple double bonds and are beneficial for health, reducing cholesterol levels and lowering the risk of heart disease. These fats are found in plant oils and fatty fish.

  • Phospholipids form the structural basis of cell membranes. They have a hydrophilic head (phosphate group) and hydrophobic tails (fatty acids), creating the bilayer structure.

  • Steroids, including cholesterol, have a four-ring structure and are involved in membrane fluidity and as precursors for hormones like testosterone and estrogen.

Synthesis and Breakdown of Polymers:

• Polymers (e.g., proteins, carbohydrates) are formed through condensation reactions (loss of water) and broken down through hydrolysis (addition of water). These processes are critical for the synthesis and breakdown of biological macromolecules.

Key Takeaways:

• Carbon is central to the structure and function of biological molecules, enabling the diversity of life.

• Carbohydrates are essential for energy storage and structural integrity in cells. Simple sugars (monosaccharides) form more complex carbohydrates (disaccharides and polysaccharides).

• Lipids serve various roles, including energy storage, membrane structure, and hormone production. Fats can be saturated, unsaturated, or hydrogenated, with varying health impacts.

• The synthesis and breakdown of macromolecules, such as carbohydrates and lipids, involve essential biochemical reactions that are vital for life.

Summary of Lecture 4: Macromolecules II: Proteins and Nucleic Acids

Dr. Marcelo Wood, Bio93

Overview:

Lecture 4 focuses on proteins and nucleic acids, two essential classes of macromolecules in cells. The lecture covers their structural characteristics, functions, and how changes in their structure can lead to diseases. Emphasis is placed on the relationship between protein structure and function, as well as the mechanisms governing protein folding, degradation, and gene expression.

Proteins:

Proteins are complex macromolecules made up of amino acids (AAs) and are involved in a wide variety of cellular functions, including catalysis, signaling, structural support, transport, and immune defense.

Amino Acids (AAs):

• Amino Acids are the building blocks of proteins. There are 20 standard amino acids, each characterized by a specific R group (side chain).

  1. Nonpolar (Hydrophobic): E.g., leucine, alanine

  2. Polar (Hydrophilic): E.g., serine, threonine

  3. Charged: E.g., lysine, glutamic acid

• Each amino acid has:

  1. Amino group (–NH₂)

  2. Carboxyl group (–COOH)

  3. Hydrogen atom

  4. Variable R group

Polypeptides and Proteins:

• Polypeptides: Chains of amino acids linked by peptide bonds (formed through dehydration synthesis). The sequence of amino acids is determined by the genetic code (DNA).

• Proteins: A functional molecule made from one or more polypeptides, folded into a specific three-dimensional shape.

Levels of Protein Structure:

Proteins are organized into four levels of structure that determine their function:

1. Primary Structure:

   • The sequence of amino acids in a polypeptide chain. This sequence is critical for the final shape and function of the protein.

2. Secondary Structure:

   • Local folding patterns of the polypeptide backbone due to hydrogen bonding. These structures include:

     • Alpha helices (coiled structures)

     • Beta-pleated sheets (folded structures)

3. Tertiary Structure:

   • The overall three-dimensional shape of a single polypeptide, determined by interactions between the R groups of the amino acids. These interactions include:

     • Hydrogen bonds

     • Ionic bonds

     • Hydrophobic interactions

     • Van der Waals forces

     • Disulfide bridges (covalent bonds)

   • The tertiary structure is crucial for protein function.

4. Quaternary Structure:

   • The structure formed when two or more polypeptides interact to form a functional protein. These subunits are held together by R group interactions.

Function of Proteins:

Proteins have diverse functions in cells, including:

• Catalysis: Enzymes speed up biochemical reactions (e.g., lactase breaks down lactose).

• Structure: Structural proteins like collagen provide support in connective tissues.

• Transport: Proteins like hemoglobin transport oxygen.

• Signaling: Proteins like insulin regulate metabolism.

• Movement: Proteins like actin and myosin are involved in muscle contraction.

• Defense: Antibodies are proteins that fight infections.

Protein Conformation and Disease:

• Sickle Cell Anemia: Caused by a single base mutation in DNA, leading to a change in the mRNA and a single amino acid substitution in hemoglobin (glutamic acid to valine). This change alters the protein’s structure, causing the red blood cells to become sickle-shaped and impairing oxygen transport.

Environmental Factors Affecting Protein Folding:

• Proteins fold into their correct conformation based on environmental conditions. Factors such as pH, temperature, and salt concentration can affect protein structure. When proteins unfold or "denature" (due to changes in the environment), they may lose their function.

Chaperone Proteins:

• Chaperones are proteins that assist in the proper folding and refolding of other proteins. They help protect proteins from misfolding and aggregation, ensuring that they achieve their correct functional shapes.

Proteasome Degradation:

• Damaged or misfolded proteins are targeted for degradation by proteasomes. This process involves tagging proteins with ubiquitin (known as the "kiss of death") and delivering them to the proteasome, where they are broken down into smaller peptides. This system is essential for maintaining protein quality control in the cell. Abnormal proteasomal degradation is linked to diseases such as cystic fibrosis, neurodegenerative disorders, and cancer.

Nucleic Acids:

Nucleic acids store and transmit genetic information. There are two types of nucleic acids: DNA and RNA.

Structure of Nucleotides:

• Nucleotides are the building blocks of nucleic acids. Each nucleotide consists of:

  1. A pentose sugar (ribose in RNA, deoxyribose in DNA)

  2. A nitrogenous base:

     • Purines (adenine [A], guanine [G]): Two-ring structure

     • Pyrimidines (cytosine [C], thymine [T] in DNA, uracil [U] in RNA): Single-ring structure

  3. A phosphate group

DNA vs. RNA:

• DNA:

  • Double-stranded

  • Contains deoxyribose as the sugar

  • Nitrogenous bases: A, T, C, G

  • Stores genetic information

  • Uses thymine (T) as a base

• RNA:

  • Single-stranded

  • Contains ribose as the sugar

  • Nitrogenous bases: A, U, C, G

  • Involved in protein synthesis and gene expression

  • Uses uracil (U) instead of thymine

Sugar-Phosphate Backbone:

• Nucleotides are linked by phosphodiester bonds, forming the backbone of nucleic acids. This is a dehydration reaction between the phosphate group of one nucleotide and the sugar of the next.

Double Helix of DNA:

• The structure of DNA is a double helix, with two strands running in opposite directions. The two strands are connected by hydrogen bonds between complementary nitrogenous bases:

  • Adenine (A) pairs with Thymine (T)

  • Cytosine (C) pairs with Guanine (G)

• The double helix is stabilized by these hydrogen bonds, which facilitate processes like DNA replication.

Key Points:

• Proteins are essential for a variety of cellular processes and their function depends on their three-dimensional structure. A single amino acid change can have profound consequences, as demonstrated in diseases like sickle cell anemia.

• The structure of DNA and RNA is crucial for genetic information storage and protein synthesis. DNA is double-stranded and stores genetic material, while RNA is single-stranded and plays a key role in translating that information into proteins.

• Chaperone proteins assist in proper folding, and proteasomes degrade misfolded proteins, ensuring cellular health.

This lecture highlights the central role of proteins and nucleic acids in cellular function, how changes in their structure can lead to diseases, and the mechanisms involved in maintaining protein quality control.

Lecture 5 Summary: Single-Cell Dynamics and Membrane Structure

Dr. Jorge Busciglio, Bio93

Overview:

Lecture 5 focuses on the structure and function of cellular membranes, the fluid mosaic model, and how organelles coordinate to carry out specialized cellular activities. It also touches on the dynamics of membrane components, their role in maintaining cell integrity, and their involvement in disease mechanisms such as HIV infection.

Key Concepts and Vocabulary:

1. Prokaryotic vs. Eukaryotic Cells:

   • Prokaryotic cells (bacteria, archaea) lack membrane-bound organelles and a nucleus.

   • Eukaryotic cells (protists, fungi, animals, plants) have a nucleus and membrane-bound organelles.

2. Organelle:

   • Membrane-bound structures in the cytoplasm, each performing specific functions within the cell (e.g., mitochondria for energy production).

3. Amphipathic (Amphiphile) Molecules:

   • Molecules that contain both hydrophobic (water-repelling) and hydrophilic (water-attracting) regions. Phospholipids, the primary building blocks of cell membranes, are amphipathic.

4. Fluid Mosaic Model:

   • A model that describes the structure of cell membranes as a dynamic and flexible layer with a variety of components (lipids, proteins, and carbohydrates) that move laterally within the membrane.

Cell Membrane Structure:

1. Plasma Membrane:

   • Thickness: Approximately 8 nm.

   • Composition:

     • Lipids: Primarily phospholipids, which are amphipathic and form the bilayer of the membrane.

     • Cholesterol: Modulates the fluidity of the membrane, stabilizing it in varying temperatures.

     • Proteins: Embedded within the bilayer, these membrane proteins regulate various functions such as transport, signaling, and cell recognition.

     • Carbohydrates: Found on the extracellular side, involved in cell-cell recognition and forming glycoproteins and glycolipids.

2. Fluid Mosaic Model:

   • Describes the cell membrane as a "mosaic" of proteins embedded in a fluid phospholipid bilayer.

   • Phospholipids can move laterally within the membrane, a property that contributes to its fluidity.

   • The fluidity of the membrane allows for flexibility, essential for cell movement, growth, and division.

   • Organisms in extreme environments can adjust membrane fluidity by changing lipid composition.

3. Cholesterol's Role:

   • Cholesterol acts as a buffer, helping to maintain membrane fluidity by preventing the membrane from becoming too rigid at low temperatures or too fluid at high temperatures.

Membrane Proteins:

1. Transmembrane Proteins:

   • Structure: These proteins span the entire membrane, often with hydrophobic regions interacting with the lipid bilayer and hydrophilic regions exposed to the aqueous environment.

   • Function: These proteins play diverse roles, including acting as receptors, channels, or carriers for molecules across the membrane.

2. Membrane Protein Functions:

   • Transport: Membrane proteins facilitate the movement of molecules into and out of the cell.

   • Receptors: Some proteins act as receptors for signaling molecules (e.g., hormones, neurotransmitters).

   • Enzymatic Activity: Some proteins catalyze chemical reactions.

   • Cell Recognition: Membrane proteins contribute to recognizing other cells or molecules, important in immune response and cell communication.

Experimental Investigation of Membrane Dynamics:

1. Lateral Drifting:

   • Phospholipids and membrane proteins can move laterally within the plane of the membrane. This movement is experimentally observed and supports the fluid mosaic model.

Membrane Receptors and Human Health:

1. HIV Infection:

   • HIV (Human Immunodeficiency Virus) targets CD4 and CCR5 receptors on host cells to gain entry.

   • The viral membrane proteins mimic the structure of natural ligands, allowing the virus to bind to and enter the host cell.

2. HIV Treatment:

   • Viral Entry Inhibitors: One class of drugs, like Maraviroc, block the CCR5 receptor, preventing HIV from entering host cells.

   • Other inhibitors target the CD4 receptor or viral surface proteins, but these drugs often have significant side effects.

Learning Outcomes:

• Cellular Activity Model: Understanding how cellular organelles work together to carry out specialized functions (e.g., a white blood cell chasing and engulfing bacteria).

• Fluid Mosaic Model: Be able to draw and explain the components of the plasma membrane, understanding the function of lipids, proteins, and carbohydrates.

• Biosynthesis of Membrane Components: Know how membrane proteins and lipids are oriented during biosynthesis and how this affects their function.

• Experimental Analysis: Understand and describe the experimental manipulation of lateral drift to probe the fluidity of cell membranes.

Key Takeaways:

• The fluid mosaic model of the membrane emphasizes the dynamic nature of the lipid bilayer, with proteins and lipids moving within it to perform essential functions.

• Membrane proteins are crucial for cell signaling, transport, and immune recognition.

• Membrane fluidity is essential for proper cellular function and is modulated by components like cholesterol.

• Understanding how viruses, like HIV, use cell membrane receptors to infect host cells opens the door for targeted treatments, such as entry inhibitors.

Lecture 6 Summary: Membrane Function, Passive & Active Transport

Dr. Jorge Busciglio, Bio93

This lecture covers the mechanisms of transport across the cell membrane, exploring passive and active transport, the role of specific proteins, and how cells maintain homeostasis. It also discusses vesicular transport, tonicity, and the physiological implications of transport dysfunction.

Key Vocabulary:

• Tonicity: Describes the relative concentration of solutes in solutions (hypotonic, isotonic, hypertonic).

• Osmosis: The movement of water across a membrane from a region of low solute concentration to high solute concentration.

• Endocytosis: Process by which cells engulf external substances to bring them inside.

• Exocytosis: The process by which cells expel materials using vesicles that fuse with the plasma membrane.

• Phagocytosis: A form of endocytosis in which large particles, like bacteria, are engulfed.

• Pinocytosis: "Cell drinking", a form of endocytosis where the cell takes in extracellular fluid.

• Hypercholesterolemia: A condition involving high cholesterol, often due to defective LDL receptors.

Learning Outcomes:

• Compare Passive & Active Transport: Understand the difference between the two types of transport across membranes, and how each process influences cell behavior.

• Predict Cell Behavior: Understand how animal and plant cells respond in different tonic environments (hypotonic, isotonic, hypertonic).

• Types of Membrane Traffic: Identify various transport methods such as direct passage, mediated passage, and vesicular transport.

• Transport System Failures: Predict the consequences when specific transport mechanisms fail (e.g., LDL receptor dysfunction in hypercholesterolemia).

• Transport Mechanisms: Draw and explain electrogenic pumps, co-transport systems, and their mechanisms.

Traffic Across the Plasma Membrane:

The plasma membrane is selectively permeable, meaning it allows certain substances to pass while blocking others. There are several mechanisms for moving molecules across the membrane:

1. Direct Passage (Simple Diffusion):

   • Small, hydrophobic molecules like gases (CO₂, O₂) and steroids can pass through the lipid bilayer directly, moving down their concentration gradient (no energy required).

2. Mediated Passage (via Transport Proteins):

   • Passive transport: Molecules like ions and large molecules can move through the membrane via channel or carrier proteins without energy input, moving down their concentration gradient (e.g., facilitated diffusion).

   • Active transport: Requires energy (typically ATP) to move molecules against their concentration gradient via carrier proteins (e.g., proton pump, sodium-potassium pump).

Examples of Transport:

1. Osmosis:

   • Water moves across a semi-permeable membrane via aquaporin channels. Osmosis is driven by differences in solute concentrations across the membrane.

2. Passive Transport (Facilitated Diffusion):

   • For example, aquaporins allow water molecules to diffuse across the membrane. Facilitated diffusion does not require energy and moves molecules down their concentration gradient through specific transport proteins.

3. Active Transport:

   • Proton Pump (H⁺ ions): This electrogenic pump moves protons across the membrane against their concentration gradient, generating a charge difference.

   • Sodium-Potassium Pump: A major active transport mechanism in animal cells. It pumps 3 Na⁺ ions out and 2 K⁺ ions into the cell, creating a gradient and electrical potential across the membrane.

Co-Transport Mechanisms:

• Co-Transport involves the use of one molecule’s gradient to drive the active transport of another molecule. For example, in plants, the H⁺ ion gradient is used to co-transport sucrose into the cell.

Vesicular Transport:

1. Endocytosis:

   • Large molecules like proteins or particles (e.g., bacteria) are engulfed by the plasma membrane and brought into the cell via vesicles. There are three types:

     • Phagocytosis: Engulfing large particles (e.g., immune cells eating bacteria).

     • Pinocytosis: Taking in extracellular fluid and solutes.

     • Receptor-Mediated Endocytosis: Specific receptors on the membrane facilitate the uptake of particular molecules (e.g., cholesterol via LDL receptors).

2. Exocytosis:

   • Molecules are expelled from the cell when vesicles containing the substances fuse with the plasma membrane. This process is essential for processes like neurotransmission and membrane renewal.

Example: Receptor-Mediated Endocytosis & Cholesterol Uptake:

• LDL (Low-Density Lipoprotein) carries cholesterol in the bloodstream. LDL binds to specific receptors on the cell membrane, triggering endocytosis. Once inside, LDL is broken down, and cholesterol is released for cellular use.

• Familial Hypercholesterolemia: A genetic condition where LDL receptors are defective, leading to the accumulation of cholesterol in the blood and an increased risk of atherosclerosis (plaque buildup in blood vessels).

Summary of Transport:

• Passive Transport: No energy required, moves molecules down their concentration gradient (e.g., simple diffusion, facilitated diffusion).

• Active Transport: Energy (ATP) required, moves molecules against their concentration gradient (e.g., proton pump, sodium-potassium pump).

• Vesicular Transport: Involves the formation of vesicles for the transport of large molecules or particles (e.g., endocytosis, exocytosis).

Conclusion:

The movement of substances across the plasma membrane is essential for cellular function and homeostasis. The cell uses a variety of mechanisms—including passive and active transport, as well as vesicular trafficking—to regulate what enters and exits the cell. The failure of these systems, such as in diseases like familial hypercholesterolemia, can have significant physiological consequences.

Lecture 7 Summary: Cytoskeleton, Mitochondria, Chloroplasts, Extracellular Matrix, and Peroxisomes

Dr. Jorge Busciglio, Bio93

This lecture explores the structure, function, and interactions of key cellular components: the cytoskeleton, mitochondria, chloroplasts, extracellular matrix, and peroxisomes. It highlights their roles in maintaining cell structure, energy production, and communication with the environment.

Key Vocabulary:

• Polymers: Large molecules made up of repeating subunits (monomers), with examples including dimers (2 units), tetramers (4 units), etc.

• Progeria: A genetic disorder that leads to premature aging, associated with mutations in nuclear lamins.

• Centriole, Centrosome: Structures involved in organizing microtubules during cell division.

• Filopodia, Lamellipodia, Pseudopodia: Cellular projections involved in cell movement and interactions with the environment.

• Cilia/Flagella: Appendages used by cells for movement or fluid transport.

Learning Outcomes:

• Understand and Illustrate Organelles: Learn the structure and function of organelles, including the cytoskeleton, mitochondria, chloroplasts, extracellular matrix, and peroxisomes.

• Cytoskeleton and Intracellular Transport: Recognize the components of the cytoskeleton (microfilaments, microtubules, and intermediate filaments), motor proteins, and their role in intracellular traffic.

• Organelles and Their Functions: Relate the structure of mitochondria, chloroplasts, and peroxisomes to their specific cellular roles.

• Extracellular Matrix: Illustrate the structure and function of the extracellular matrix, including its interaction with the cytoskeleton and cellular functions.

The Cytoskeleton:

The cytoskeleton is a network of protein filaments that provide structural support and facilitate movement within the cell. It is composed of three major types of fibers:

1. Microfilaments (MF):

   • Structure: Solid rods made of actin subunits, forming a twisted double chain.

   • Function:

     • Maintain cell shape (e.g., microvilli in intestinal cells).

     • Facilitate short-distance intracellular transport with the help of myosin motor proteins.

     • Support cell motility (e.g., crawling movement, muscle contraction).

   • Dynamics: Microfilaments are highly dynamic, with rapid polymerization at the + end and depolymerization at the - end.

2. Intermediate Filaments (IF):

   • Structure: Supercoiled into thick cables (e.g., keratins, neurofilaments).

   • Function:

     • Provide mechanical support and resist tension.

     • Anchor the cell and nuclear components (e.g., nuclear lamina).

   • Progeria: Mutations in lamin proteins, a type of intermediate filament, cause accelerated aging due to defective nuclear assembly and chromosome organization.

3. Microtubules (MT):

   • Structure: Hollow cylindrical rods made of tubulin dimers.

   • Function:

     • Maintain cell shape and organize internal components.

     • Provide tracks for the transport of organelles, vesicles, and chromosomes during cell division.

     • Interact with motor proteins like kinesins (move toward the + end) and dyneins (move toward the - end).

   • Centrosomes and Centrioles: Centrosomes organize microtubules, and centrioles play a key role in cell division.

Motor Proteins:

• Function: Motor proteins (e.g., kinesins, dyneins) move cargo along microtubules, powered by ATP.

• Example: Kinesins move organelles toward the + end of microtubules (toward the cell periphery), while dyneins move cargo toward the - end (toward the center of the cell).

Cilia and Flagella:

• Structure: Microtubules arranged in a "9+2" pattern, with a central pair of microtubules surrounded by nine pairs.

• Function:

  • Cilia: Shorter, numerous projections that move fluids over cell surfaces (e.g., in the respiratory tract).

  • Flagella: Longer projections that help cells move (e.g., sperm cells).

• Ciliopathies: Diseases caused by defects in cilia function, leading to issues like respiratory infections and infertility.

Extracellular Matrix (ECM):

The ECM is a complex network of glycoproteins, including collagen fibers, that provides structural support to tissues and facilitates communication between cells.

• Function:

  • Anchors cells in tissue.

  • Mediates cell signaling and tissue architecture.

  • Connects to the cell cytoskeleton via integrins, which link ECM proteins (e.g., fibronectin) to intracellular filaments.

Mitochondria:

• Function: Often referred to as the "powerhouse" of the cell, mitochondria generate ATP via cellular respiration.

• Structure: Enclosed by two membranes: an outer membrane and an inner membrane with folds called cristae.

• Semiautonomous: Mitochondria can replicate and grow independently within the cell.

• Location: Mitochondria are mobile and can move along microtubules within the cytoplasm.

Chloroplasts:

• Function: Found in plant cells and algae, chloroplasts are the site of photosynthesis, converting sunlight into chemical energy (glucose).

• Structure: Similar to mitochondria, chloroplasts have a double membrane and contain thylakoids (flattened sacs) where light reactions of photosynthesis occur.

Peroxisomes:

• Function: Peroxisomes are membrane-bound organelles that detoxify harmful substances and break down fatty acids.

• Byproducts: They produce hydrogen peroxide (H₂O₂), which is toxic, but contain enzymes (e.g., catalase) to convert H₂O₂ into water.

• Structure: Formed from proteins and lipids in the cytosol (not part of the endomembrane system).

Conclusion:

This lecture provides a comprehensive overview of the cytoskeleton, energy-producing organelles (mitochondria and chloroplasts), and other important cellular components like peroxisomes and the extracellular matrix. Understanding the structure and function of these organelles is essential for understanding how cells maintain their shape, communicate, move, and perform essential tasks like energy production and detoxification.

Lecture 8 Summary: Nucleus, Ribosomes, and Endomembrane System

Dr. Jorge Busciglio, Bio93

This lecture covers the structure, function, and interconnections of key organelles involved in protein synthesis, cellular transport, and maintenance, including the nucleus, ribosomes, and the endomembrane system (which consists of the endoplasmic reticulum, Golgi apparatus, lysosomes, and peroxisomes).

Key Vocabulary:

• Chromatin: DNA-protein complex in the nucleus, involved in gene expression and DNA packaging.

• Gonads: Reproductive organs (ovaries in females, testes in males) involved in gamete and hormone production.

• Lumen: The internal space within organelles like the endoplasmic reticulum or Golgi apparatus.

• Autophagy: The process by which a cell recycles its own damaged organelles or components.

• Autosomal Recessive Inheritance: A type of inheritance pattern where two copies of an abnormal gene must be inherited for the trait to be expressed.

Learning Objectives:

1. Define the structure and function of the nucleus and describe its components (e.g., chromatin, nuclear envelope).

2. Understand the structure and function of ribosomes and how they synthesize proteins.

3. Describe the structure and function of the endoplasmic reticulum (ER), including the differences between smooth ER (sER) and rough ER (rER).

4. Explain the structure and function of the Golgi apparatus and its role in modifying, sorting, and packaging proteins.

5. Identify lysosomes and peroxisomes and predict the consequences of their malfunction, especially in lysosomal storage disorders.

Nucleus:

• Function: The nucleus houses the cell's genetic material (DNA) and is responsible for mRNA synthesis, which is crucial for protein production.

• Structure:

  • Chromatin: DNA wrapped around proteins (histones) that is loosely organized for transcription.

  • Nucleolus: A region within the nucleus where ribosomal RNA (rRNA) is synthesized and ribosomal subunits are assembled.

  • Nuclear Envelope: Double membrane that encloses the nucleus, with nuclear pores made of proteins (nucleoporins) that regulate the transport of molecules like mRNA and ribosomal subunits.

  • Nuclear Localization Signals: Tags on proteins that allow them to pass through nuclear pores.

Ribosomes:

• Function: Ribosomes are responsible for protein synthesis (translation of mRNA into proteins).

• Structure: Ribosomes are made of rRNA and proteins, consisting of two subunits:

  • Large subunit and small subunit.

• Types of Ribosomes:

  • Free Ribosomes: Float freely in the cytoplasm, synthesizing cytosolic proteins.

  • Bound Ribosomes: Attached to the rough ER (rER), synthesizing membrane proteins and secreted proteins.

Endoplasmic Reticulum (ER):

• Function: The ER is involved in protein and lipid synthesis, detoxification, and calcium storage.

• Structure: The ER is a network of membranous tubules and cisternae (internal stacks), continuous with the nuclear envelope.

1. Smooth ER (sER):

   • No ribosomes attached.

   • Functions:

     • Lipid synthesis (e.g., phospholipids).

     • Steroid hormone production (e.g., in gonads).

     • Carbohydrate metabolism (e.g., glycogen breakdown in liver cells).

     • Detoxification (e.g., in liver cells to metabolize drugs and poisons).

     • Calcium sequestration: In muscle cells, regulates calcium for contraction; in secretory cells, regulates vesicle secretion.

2. Rough ER (rER):

   • Ribosomes attached to the membrane.

   • Functions:

     • Protein processing: Proteins synthesized by bound ribosomes are processed within the rER.

     • Membrane factory: Synthesizes phospholipids and membrane proteins, which are transferred in vesicles to other organelles or the plasma membrane.

Golgi Apparatus:

• Structure: The Golgi is made up of flattened membranous sacs (cisternae) with two faces:

  • Cis face: The receiving side, where vesicles from the ER fuse.

  • Trans face: The shipping side, where vesicles bud off and transport modified proteins to their final destinations.

• Function:

  • Modifies proteins and lipids received from the ER (e.g., glycosylation).

  • Synthesizes polysaccharides.

  • Sorts and packages proteins into vesicles for transport to the plasma membrane, lysosomes, or other organelles.

Lysosomes:

• Function: Lysosomes are the cell's digestive organelles, containing hydrolytic enzymes that break down macromolecules.

  • Types of digestion:

    • Autophagy: Recycling of damaged organelles.

    • Phagocytosis: Breaking down food vacuoles.

    • Bacterial digestion: Destroying bacterial invaders.

• Lysosomal Membrane: Contains proton pumps that maintain an acidic internal environment, optimal for enzyme activity.

• Lysosomal Storage Disorders (LSDs): Mutations in lysosomal enzymes can lead to disorders like Tay-Sachs, Gaucher, and Pompe diseases, which result in the accumulation of undigested materials within lysosomes.

Peroxisomes:

• Function: Peroxisomes are involved in detoxifying harmful substances, such as alcohol, and breaking down fatty acids.

  • They contain enzymes that produce hydrogen peroxide (H₂O₂) as a byproduct, which is toxic but is broken down into water by catalase.

• Structure: Membrane-bound organelles that are not part of the endomembrane system but are involved in metabolic functions and detoxification.

Conclusion:

This lecture focused on the nucleus, ribosomes, and the endomembrane system, providing an in-depth look at how these organelles collaborate to maintain cellular function. The nucleus stores genetic information, ribosomes synthesize proteins, and the endomembrane system (ER, Golgi, lysosomes) processes, sorts, and transports proteins and lipids. Understanding the role of these organelles is crucial for comprehending cellular organization, metabolism, and the consequences of organelle malfunctions, such as lysosomal storage disorders.

Lecture 9 Summary: Cell Communication

Dr. Jorge Busciglio, Bio93

This lecture focuses on the mechanisms of cell communication, which are essential for the coordination of activities in multicellular organisms and even in unicellular organisms. Cell signaling is a multi-step process that allows cells to respond to changes in their environment, and it involves the reception, transduction, and response to signals.

Key Vocabulary:

• Hormone: Chemical messengers that travel long distances to target cells.

• Synapsis: The process of communication between nerve cells via neurotransmitters.

• Transduction: The process of converting a signal into a cellular response.

• Ligand: A molecule that binds to a receptor to trigger a signaling pathway.

• Paracrine: Signaling where molecules act locally on nearby cells.

• Endocrine: Long-distance signaling via hormones traveling through the circulatory system.

• Kinase: An enzyme that adds phosphate groups to proteins, often activating them.

• Phosphatase: An enzyme that removes phosphate groups from proteins, typically deactivating them.

• Proprioception: The body's ability to sense its position in space, often involving cellular signaling.

Learning Objectives:

1. Signal Transduction Pathway: Understand the three stages—reception, transduction, and response—and be able to illustrate them.

2. Reception: Learn the different types of signals (e.g., hormones, neurotransmitters) and their receptors, and predict how structural changes in receptors may affect function.

3. Receptor Types: Compare different types of receptors like GPCRs, TKRs, and intracellular receptors, understanding their locations, structures, and modes of action.

Overview of Cell Communication:

• Importance: Cell communication is critical for the coordination of cellular functions in multicellular organisms and also plays a role in unicellular organisms.

• Conservation: Many cell signaling mechanisms are highly conserved across species.

Types of Signals:

1. Secreted Signals that Act Locally:

   • Paracrine signaling: Signals act on nearby cells (e.g., growth factors).

   • Synaptic signaling: Neurotransmitters act in nerve cell communication.

2. Secreted Signals that Act at Distant Sites:

   • Hormones: Travel through the circulatory system (in animals) or vascular systems (in plants) to reach target cells. Examples include insulin (animal) and ethylene (plant).

3. Intracellular Signals:

   • These signals operate within the cell or between adjacent cells.

4. Cell Surface Signals:

   • FC receptors on white blood cells (WBC) bind to antibodies, which helps WBCs recognize and engulf pathogens like bacteria.

Reception of Signals:

• Signal Reception: Occurs when a signal (ligand) binds to a receptor, causing a change in the receptor's location or shape.

  • Types of Receptors:

    1. Plasma Membrane (Surface) Receptors: These receptors interact with hydrophilic (water-soluble) ligands.

    2. Cytoplasmic/Nuclear Receptors: These interact with hydrophobic (lipid-soluble) ligands that can pass through the cell membrane.

Types of Receptors:

1. G-Protein-Coupled Receptors (GPCRs):

   • Ligands include hormones, neurotransmitters, and sensory molecules (e.g., vision, smell).

   • Over 1000 GPCRs have been identified in humans, and more than 60% of modern medicines target GPCR pathways.

   • Function: GPCRs activate G-proteins, which in turn regulate downstream signaling pathways.

2. Tyrosine Kinase Receptors (TKRs):

   • Ligands are typically growth factors.

   • Activate multiple cellular responses, including growth and differentiation.

   • Abnormal activation of TKRs can lead to cancer, and drugs targeting these receptors are used to treat cancer.

3. Ligand-Gated Ion Channels:

   • These channels open in response to ligand binding, allowing ions like Na+ or Ca2+ to flow into or out of the cell.

   • Important for nerve cell communication and muscle contraction.

4. Intracellular Receptors:

   • Ligands like steroid hormones, thyroid hormones, and nitric oxide (NO) can cross the cell membrane and bind to intracellular receptors.

   • These hormone-receptor complexes act as transcription factors, regulating gene expression directly.

Signal Transduction:

• Transduction Mechanisms:

  1. Protein Phosphorylation Cascades: One protein activates another by adding phosphate groups, triggering a series of events inside the cell.

  2. Second Messengers: Molecules like calcium, IP3, or cAMP act as intermediates in signaling pathways, amplifying the signal and spreading it throughout the cell.

Example of Cell Signaling in Immune Response:

• White Blood Cells (WBCs) use surface receptors to recognize and respond to pathogens:

  1. Signal: Bacterial molecules activate receptors on WBCs.

  2. Transduction: WBCs undergo cytoskeletal changes (e.g., extending pseudopodia).

  3. Response: WBCs engulf and digest the bacteria through phagocytosis. Lysosomes fuse with the phagocytic vesicle to digest the pathogen.

Conclusion:

Cell communication is essential for the proper function of both individual cells and multicellular organisms. The process involves complex signaling pathways that include signal reception, transduction, and response. Different types of receptors (GPCRs, TKRs, ion channels, and intracellular receptors) are involved in detecting and responding to various signals, ensuring that cells can react to their environment appropriately. These pathways are highly conserved and crucial for functions such as immune response, growth, and homeostasis.

Lecture 10 Notes: ATP and Enzymes

Dr. Ian Smith, Bio93
Unit III: Powering the Cell

Key Vocabulary:

• Metabolism: The total of all chemical reactions within an organism.

• Free Energy: Energy available to do work (ΔG).

• Endergonic: Reactions that require energy input (positive ΔG).

• Exergonic: Reactions that release energy (negative ΔG).

• Hydrolysis: A chemical process that breaks bonds by adding water, often releasing energy.

• Enzyme: Biological catalysts that speed up chemical reactions.

Learning Outcomes:

• Describe the structure of ATP and how it powers cellular work.

• Predict if a reaction is endergonic or exergonic based on free energy changes.

• Explain the relationship between free energy and stability.

• Understand how enzymes speed up reactions by lowering activation energy (EA).

• Predict how enzyme activity can change based on temperature and pH.

Bioenergetics:

• The study of how energy flows through living organisms.

• Cells constantly perform chemical work, transport work, and mechanical work, all of which require energy.

Energy in Cells:

• First Law of Thermodynamics: Energy can be transferred and transformed, but not created or destroyed.

• Cells use chemical reactions (metabolism) to generate energy.

Chemical Reactions:

• Exergonic Reactions: Release energy (negative ΔG). Example: ATP hydrolysis releases energy to drive cellular work.

• Endergonic Reactions: Require energy input (positive ΔG). Example: protein synthesis.

Energy Coupling:

• Cells couple exergonic and endergonic reactions using ATP to efficiently transfer energy.

• ATP mediates energy coupling by providing a quick source of energy for cellular processes.

ATP:

• Structure: ATP consists of adenine (a nitrogenous base), ribose (a sugar), and three phosphate groups.

• Hydrolysis of ATP: When ATP is hydrolyzed (ATP → ADP + Pi), energy is released.

• The phosphate groups in ATP store potential energy, like a compressed spring.

• Energy Release: The energy from ATP hydrolysis is used to drive chemical, mechanical, or transport work in cells.

Enzymes:

• Enzymes are proteins that lower the activation energy (EA) of a chemical reaction, speeding up the reaction without being consumed in the process.

• Enzymes have specific active sites that bind to substrates and facilitate the reaction.

Energy Profile of a Reaction:

• Activation Energy (EA): The energy required to start a reaction.

• Enzymes lower the EA, allowing reactions to occur more easily and faster.

• Without enzymes, reactions would take much longer.

How Enzymes Work:

• Enzymes bind to substrates to form an enzyme-substrate complex.

• Enzymes lower the activation energy by:

  • Orienting substrates correctly.

  • Straining bonds in substrates, making them easier to break.

  • Providing a favorable environment for the reaction.

Factors Affecting Enzyme Activity:

• Temperature: Enzymes work optimally at a specific temperature. High temperatures can denature enzymes, while low temperatures can slow their activity.

• pH: Enzymes have an optimal pH range. Extreme pH values can alter enzyme structure, reducing activity.

Regulation of Enzyme Activity:

1. Competitive Inhibition: An inhibitor competes with the substrate for binding to the active site.

   • Example: Penicillin is a competitive inhibitor that blocks bacterial enzyme activity necessary for cell wall synthesis.

2. Noncompetitive Inhibition: An inhibitor binds to a site other than the active site, causing a conformational change in the enzyme that reduces its activity.

   • Example: Cyanide is a noncompetitive inhibitor that blocks the electron transport chain by binding to cytochrome oxidase.

Summary of Key Concepts:

• ATP is the primary energy carrier in cells, releasing energy through hydrolysis.

• Enzymes speed up chemical reactions by lowering activation energy and are crucial for controlling cellular processes.

• Enzyme Activity is influenced by factors like temperature, pH, and inhibition (competitive or noncompetitive).

Next Lecture (Lecture 11: Cellular Respiration):

• Focus will be on understanding the inputs and outputs of cellular respiration, but do not memorize detailed steps of glycolysis or the electron transport chain (ETC). Instead, focus on a high-level summary of what happens in these processes.

Lecture 11 Notes: Cellular Respiration

Dr. Ian Smith, Bio93
Zamponi et al., 2018

Key Vocabulary:

• Catabolism: Breakdown of larger molecules into smaller ones, releasing energy.

• Substrate-level Phosphorylation: ATP synthesis where a phosphate group is transferred directly from a substrate molecule to ADP.

• Glycolysis: The process of breaking down glucose into pyruvate, producing small amounts of ATP and NADH.

• Chemiosmosis: The movement of ions (protons) across a membrane to generate ATP through ATP synthase.

• Fermentation: Anaerobic pathway to regenerate NAD+ from NADH, producing ATP in the absence of oxygen.

Learning Objectives:

• Understand redox reactions and how electron transfer drives cellular respiration.

• Learn the steps of cellular respiration (inputs/outputs), where each occurs in the cell, and the amount of ATP generated.

• Explore the role of chemiosmosis in ATP production.

• Predict consequences of blocking different steps in cellular respiration.

Overview of Cellular Respiration:

• Cellular respiration refers to the catabolic process (exergonic, energy-releasing) that generates ATP.

• The transfer of electrons in redox reactions is central to cellular respiration:

  • Oxidation: Loss of electrons (increases positive charge).

  • Reduction: Gain of electrons (reduces positive charge).

  • Key Reaction: Glucose (C6H12O6) is oxidized, and oxygen (O2) is reduced in the process:C6H12O6+6O2→6CO2+6H2OC6H12O6+6O2→6CO2+6H2O

  • ΔG = -686 kcal (energy is released).

Electron Transport:

• Organic molecules like glucose store potential energy in electron arrangements.

• NADH acts as an electron carrier, transferring electrons from glucose to the electron transport chain (ETC) in the mitochondria.

  • NADH is formed by dehydrogenase enzymes, which strip electrons and protons (H atoms) from glucose, converting NAD+ into NADH.

Stages of Cellular Respiration:

Cellular respiration occurs in three main stages:

1. Glycolysis (in the cytosol)

2. Pyruvate Oxidation (in the mitochondria)

3. Citric Acid Cycle (Krebs Cycle) (in the mitochondrial matrix)

4. Oxidative Phosphorylation (Electron Transport Chain & Chemiosmosis) (inner mitochondrial membrane)

Stage 1: Glycolysis (Cytosol)

• Input: 1 molecule of glucose (C6H12O6)

• Output: 2 molecules of pyruvate, 2 ATP (via substrate-level phosphorylation), and 2 NADH.

• Description: Glycolysis splits glucose into two pyruvate molecules. It provides substrates for the Citric Acid Cycle and Oxidative Phosphorylation.

  • Substrate-level phosphorylation: ATP is generated directly through the transfer of a phosphate group from a substrate molecule (e.g., from 1,3-bisphosphoglycerate in step 7 and 10 of glycolysis).

Stage 2: Pyruvate Oxidation (Mitochondrial Matrix)

• Input: 2 molecules of pyruvate (from glycolysis)

• Output: 2 molecules of Acetyl-CoA, 2 NADH, 2 CO2

• Description: Each pyruvate enters the mitochondrion and is converted into Acetyl-CoA, which enters the Citric Acid Cycle.

  • Active transport is required for pyruvate to enter the mitochondria.

Stage 3: Citric Acid Cycle (Krebs Cycle) (Mitochondrial Matrix)

• Input: 2 molecules of Acetyl-CoA

• Output: 4 CO2, 6 NADH, 2 FADH2, 2 ATP (via substrate-level phosphorylation)

• Description: Acetyl-CoA enters the citric acid cycle, where it is oxidized to produce CO2 and high-energy electron carriers (NADH, FADH2).

  • Some cells produce GTP instead of ATP during this step.

Stage 4: Oxidative Phosphorylation (Inner Mitochondrial Membrane)

• Input: NADH, FADH2 (electron carriers), O2

• Output: 32 ATP (via chemiosmosis), H2O

• Description:

  • Electron Transport Chain (ETC): Electrons from NADH and FADH2 are passed through a series of membrane proteins, moving from less electronegative to more electronegative compounds.

  • Proton Pumps: As electrons move through the ETC, protons (H+) are pumped into the intermembrane space, creating a proton gradient.

  • Oxygen is the final electron acceptor, forming water (H2O) with electrons and protons.

  • The proton gradient drives ATP synthesis via chemiosmosis.

Chemiosmosis:

• Proton-motive force: The flow of protons (H+) back through ATP synthase, which catalyzes the conversion of ADP + Pi into ATP.

• ATP Synthase: The protons flow through this enzyme, which acts like a rotary motor, facilitating ATP formation.

  • This process is similar to water flowing over a waterwheel to generate mechanical energy.

Fermentation (Anaerobic Respiration):

• When oxygen is not available, fermentation occurs to regenerate NAD+ from NADH, allowing glycolysis to continue producing ATP.

  • Alcohol Fermentation: Converts pyruvate to ethanol and CO2 (occurs in yeast cells).

  • Lactic Acid Fermentation: Converts pyruvate to lactate (occurs in muscle cells during intense exercise).

ATP Yield from Cellular Respiration:

• Total ATP production from one molecule of glucose:

  • 32 ATP generated through the three stages (Glycolysis, Citric Acid Cycle, and Oxidative Phosphorylation).

Effects of Blocking Cellular Respiration:

• If glycolysis, citric acid cycle, or oxidative phosphorylation is blocked:

  • ATP production would be significantly reduced.

  • Electron transport chain inhibitors (e.g., cyanide) would stop the ETC and prevent ATP production.

  • Lack of oxygen would halt the ETC, leading to the need for anaerobic fermentation to continue ATP production (less efficient).

Conclusion:

• Cellular respiration is a complex process involving several stages where glucose is oxidized to produce ATP.

• The process is highly efficient, with chemiosmosis being a key mechanism for ATP production.

• The steps of cellular respiration (glycolysis, pyruvate oxidation, citric acid cycle, and oxidative phosphorylation) are tightly regulated and essential for cell function.

Lecture 12: Photosynthesis - Bio 93

Dr. Smith
Pearson Chapter 10

Key Terms in Photosynthesis:

• Autotroph: Organisms that produce their own food (organic compounds) from light or chemical energy.

• Photoautotroph: Organisms that use light energy to synthesize organic compounds (e.g., plants, algae, cyanobacteria).

• Mesophyll Cells: Cells in plant leaves where photosynthesis occurs.

• Stomata: Pores in leaves that allow gases (CO2 and O2) to enter and exit.

• Chloroplasts: Organelles in plant cells responsible for photosynthesis.

  • Stroma: The fluid-filled space inside the chloroplasts surrounding the thylakoids.

  • Thylakoids: Membrane-bound sacs within the chloroplasts where light-dependent reactions occur.

  • Thylakoid Lumen: The interior space of the thylakoids where protons accumulate during light reactions.

Key Energy Terms:

• Redox Reactions: Reactions involving the transfer of electrons (oxidation-reduction).

  • OIL RIG: Oxidation is the loss of electrons, Reduction is the gain of electrons.

  • LEO GER: Loss of Electrons is Oxidation, Gain of Electrons is Reduction.

• NADP+/NADPH: NADP+ is the electron acceptor, and NADPH is its reduced form, used in the Calvin cycle.

• ATP Synthesis / Photophosphorylation: The production of ATP using light energy.

Calvin Cycle (Dark Reactions):

• Carbon Fixation: The process of incorporating CO2 into an organic molecule.

• Fixation/Reduction/Regeneration: The three stages of the Calvin cycle.

  • G3P (Glyceraldehyde-3-phosphate): The 3-carbon sugar produced in the Calvin cycle, which is used to form glucose and other organic compounds.

Learning Outcomes:

• Role of Photosynthesis: Understand how photosynthesis sustains life on Earth by converting light energy into chemical energy, cycling essential molecules like CO2 and O2.

• Chloroplast Structure: Learn the function of chloroplast membranes and compartments in photosynthesis.

• Light Absorption: Describe how chlorophyll absorbs light and the resulting electron transport in photosynthesis.

• Electron Transport Chain: Understand the components of the photosynthetic electron transport chain and the redox reactions involved.

• Chemiosmosis: Describe how the proton gradient is formed to produce ATP during light reactions.

• Comparison with Mitochondria: Compare photosynthesis in chloroplasts and respiration in mitochondria in terms of energy conversion.

• Calvin Cycle: Understand the steps of carbon fixation, reduction, and regeneration in the Calvin cycle.

The Reciprocity of Photosynthesis and Respiration:

• Photosynthesis and cellular respiration are interdependent processes. Together, they form a cycle that converts energy into usable forms and cycles essential molecules like carbon dioxide and oxygen.

  • Plants: Primary producers (autotrophs) that use sunlight, water, and CO2 to produce organic compounds.

  • Other Organisms: Consumers (heterotrophs) that rely on plants for energy.

Autotrophs & Photoautotrophs:

• Autotrophs: Organisms that produce their own organic compounds (sugars) using energy from light or chemicals.

• Photoautotrophs: Use light energy to make organic compounds. Examples include:

  • Land: Plants (convert CO2 and water into organic compounds).

  • Oceans: Eukaryotic algae, unicellular algae, and cyanobacteria (prokaryotes).

Chloroplasts: The Site of Photosynthesis:

• Structure of Chloroplasts:

  • Stroma: Fluid-filled region where the Calvin cycle occurs.

  • Thylakoids: Membrane-bound structures where light-dependent reactions take place.

  • Thylakoid Lumen: The space inside the thylakoids.

  • Granum: Stack of thylakoid membranes.

Redox Equation for Photosynthesis:

• General Equation:
  6CO2+6H2O→C6H12O6+6O26CO2​+6H2​O→C6​H12​O6​+6O2​

  • CO2 is reduced (gains electrons to form glucose).

  • Water is oxidized (loses electrons to form oxygen).

• In photosynthesis, light energy is converted into chemical energy:

  • Electrons increase in energy potential as they move from water to sugar.

  • OIL RIG: Water undergoes oxidation (losing electrons) while CO2 undergoes reduction (gaining electrons).

Ingredients for Photosynthesis:

• CO2: Enter through stomata.

• H2O: Absorbed by roots and transported to leaves via veins.

• Light Energy: Captured by pigments in the thylakoid membrane of chloroplasts.

Why Are Chloroplasts Green?:

• Chlorophyll absorbs most wavelengths of light, but reflects green light, giving plants their green color.

• Absorption Spectra: Graph showing the absorption of light by chlorophyll and other pigments.

• Action Spectrum: The rate of photosynthesis corresponding to light absorption by pigments.

How Light Energy is Captured and Converted:

• When chlorophyll absorbs light, a photon excites electrons, raising them to a higher energy state.

• Chlorophyll absorbs light most effectively in the blue (~450 nm) and red (~680 nm) wavelengths.

Two Processes of Photosynthesis:

1. Light Reactions: Occur in the thylakoid membranes.

   • Energy source: Light.

   • Output: ATP, NADPH, and O2 (from the splitting of water).

2. Dark Reactions (Calvin Cycle): Occur in the stroma.

   • Energy source: ATP and NADPH produced in light reactions.

   • Output: G3P (glyceraldehyde-3-phosphate), which is used to form sugars.

Light Reactions in Thylakoid Membranes:

• Light energy is captured by chlorophyll and other pigments in the photosystems.

• Photosystem II (PSII) absorbs light, excites electrons, and splits water to release O2.

• Photosystem I (PSI) accepts electrons from PSII, which are used to form NADPH.

• The electron transport chain transports excited electrons from PSII to PSI, generating a proton gradient.

• ATP synthase uses the proton gradient to generate ATP through photophosphorylation.

Comparison with Mitochondria:

• Mitochondria: Use food molecules (glucose) to make ATP via oxidative phosphorylation.

• Chloroplasts: Use light energy to make ATP and NADPH via photophosphorylation in the light reactions.

  • Both generate ATP through chemiosmosis.

  • Mitochondria use chemical energy from food, while chloroplasts use light energy.

Calvin Cycle (Dark Reactions):

• Purpose: To convert CO2 into organic molecules (sugars).

• Steps:

  1. Carbon Fixation: CO2 is incorporated into a 5-carbon sugar, RuBP.

  2. Reduction: ATP and NADPH are used to convert the 3-carbon compound into G3P (Glyceraldehyde-3-phosphate).

  3. Regeneration: Some G3P molecules are used to regenerate RuBP, completing the cycle.

• Inputs: CO2, ATP, NADPH.

• Outputs: G3P (used to form glucose), ADP, Pi, NADP+.

Summary:

• Photosynthesis consists of two main stages: light reactions (in thylakoid membranes) and the Calvin cycle (in the stroma).

• The light reactions convert solar energy into chemical energy (ATP and NADPH).

• The Calvin cycle uses ATP and NADPH to convert CO2 into G3P, a 3-carbon sugar.

• This process sustains life on Earth by producing organic compounds and cycling carbon and oxygen.

Lecture 13: The Molecular Basis of Inheritance

Dr. Kim Green
Bio 93

Key Nomenclature for DNA:

• Transformation: A process in which external genetic material is introduced into a cell, causing a change in its phenotype.

• Bacteriophages (phages): Viruses that infect bacteria, used in molecular genetics research.

• Double Helix: The spiral structure of DNA, consisting of two complementary strands.

• DNA Strand: A long chain of nucleotides forming the structure of DNA.

• Anti-parallel Strands: DNA strands that run in opposite directions, ensuring correct base pairing.

• Base Pairing: The specific pairing of nitrogenous bases in DNA: Adenine (A) pairs with Thymine (T), and Guanine (G) pairs with Cytosine (C).

• DNA Replication: The process of copying DNA to ensure genetic information is passed on during cell division.

• Semiconservative Replication: A method of DNA replication where each new DNA molecule consists of one old strand and one newly synthesized strand.

Core Concepts in DNA Inheritance:

• DNA is the genetic material: DNA carries the genetic instructions for the development and functioning of living organisms.

• DNA forms a double helix structure: DNA consists of two intertwined strands forming a helix, held together by base pairs.

• Base pairing: Purines (A, G) pair with pyrimidines (T, C) in a specific manner to maintain the structure of DNA.

• DNA replication is semi-conservative: Each new DNA molecule consists of one old strand and one newly synthesized strand.

• Complexity of DNA replication: DNA replication involves multiple enzymes and steps, ensuring the accurate duplication of genetic material.

A Brief History of DNA:

• 1850s - Gregor Mendel: Proposed the concept of "hereditary factors" (genes).

• 1869 – Friedrich Miescher: Discovered “nucleins” from pus (precursor to identifying DNA).

• 1881 – Albrecht Kossel: Identified that nucleins are composed of five distinct nucleotides, renaming them DNA.

• 1875-1890s – Meiosis and Mitosis: Cytological work leads to understanding of cell division.

• 1902 – Walter Sutton: Proposed the chromosome theory of inheritance.

• 1930s – Thomas Morgan: Demonstrated that genes are located on chromosomes.

Experiments Leading to DNA as Genetic Material:

Griffith’s Experiment (1928):

• Griffith discovered the process of transformation in bacteria. He showed that heat-killed pathogenic bacteriacould transfer their genetic material to nonpathogenic bacteria, making them virulent.

Avery's Experiment (1943):

• Dr. Oswald Avery identified that DNA was the transforming substance responsible for the change in bacterial characteristics observed in Griffith's experiment.

Evidence that Viral DNA Can Program Cells (Hershey and Chase, 1952):

• Bacteriophages (phages) are viruses that infect bacteria, composed of DNA and protein.

• Experiment 1: Labeled phage protein with radioactive sulfur (35S) and phage DNA with radioactive phosphorus (32P).

  • Results: The phage DNA (labeled with phosphorus) entered the bacterial cell and was passed on to the next generation, confirming that DNA is the genetic material, not protein.

  • Phage Protein: Found outside the bacterial cell (in the liquid).

  • Phage DNA: Found inside the bacterial cells (in the pellet).

Chargaff's Rules:

• Erwin Chargaff's Observations (1940s):

  • The amount of A always equals T and the amount of C equals G in any given DNA sample.

  • In humans, the ratio is:

    • A = 30%, T = 30%, G = 20%, C = 20%.

Building the Structural Model of DNA:

• X-ray Crystallography (Rosalind Franklin & Maurice Wilkins):

  • Franklin's X-ray diffraction image revealed the helical structure of DNA.

  • The width of the helix and spacing between nitrogenous bases indicated that DNA consists of two strands, forming a double helix.

• Watson and Crick (1953):

  • Using Franklin's data, Watson and Crick proposed the double-helix model of DNA:

    • The two strands of DNA are anti-parallel (run in opposite directions).

    • Base pairing: Adenine (A) pairs with Thymine (T), and Guanine (G) pairs with Cytosine (C), as suggested by Chargaff’s rules.

    • The structure is stabilized by hydrogen bonds between complementary bases.

The Structure of DNA:

• Sugar-Phosphate Backbone: The structural framework of DNA, consisting of alternating sugar (deoxyribose) and phosphate groups.

• Nitrogenous Bases:

  • Purines: Adenine (A) and Guanine (G).

  • Pyrimidines: Cytosine (C) and Thymine (T).

• Base Pairing:

  • A-T: Two hydrogen bonds.

  • G-C: Three hydrogen bonds.

DNA Replication: Semiconservative Model:

• Replication Process: DNA replication involves the unwinding of the parental DNA molecule and the synthesis of two new complementary strands.

• Semiconservative Replication: In this model, each of the two resulting DNA molecules consists of one old strand (from the parent) and one newly synthesized strand.

• Key Steps:

  1. Parental Molecule: The original DNA molecule consists of two strands.

  2. Separation of Strands: The two strands of the parental DNA are separated to serve as templates.

  3. Synthesis of New Strands: New nucleotides are added to the templates based on base pairing rules, forming new daughter strands.

Summary of DNA Replication:

• Base Pairing: The principle of base pairing allows the DNA strands to be complementary, ensuring that one strand acts as a template for the other.

• Enzymes Involved:

  • Helicase: Unwinds the DNA double helix.

  • DNA polymerase: Adds new nucleotides to the growing strand.

  • Primase: Synthesizes short RNA primers for DNA polymerase to start replication.

  • Ligase: Seals the gaps between the newly synthesized DNA fragments (Okazaki fragments on the lagging strand).

Conclusion:

• DNA is the genetic material responsible for inheritance.

• It has a double-helix structure and undergoes semi-conservative replication, ensuring the accurate copying of genetic information.

• Base pairing and complementarity are crucial for maintaining the integrity of the genetic code across generations.

Lecture 14: DNA Replication and Repair

Dr. Kim Green
Bio 93

Concepts from Last Lecture:

• DNA is the genetic material

• DNA structure: Double helix

• Base pairing: Purines (A, G) pair with pyrimidines (T, C)

• DNA replication is semi-conservative (each daughter DNA molecule contains one old strand and one new strand)

• Replication is complex and requires many enzymes

Vocabulary:

• DNA Replication: The process of copying DNA before cell division.

• Semiconservative Replication: Each DNA molecule consists of one original strand and one newly synthesized strand.

• Origin of Replication: The specific location on the DNA where replication begins.

• Helicase: An enzyme that unwinds the DNA double helix.

• RNA Primase: An enzyme that synthesizes RNA primers for DNA replication.

• Topoisomerase: An enzyme that prevents the DNA from supercoiling ahead of the replication fork by creating temporary breaks and resealing the DNA.

• Single Strand Binding Proteins (SSBs): Proteins that stabilize single-stranded DNA during replication.

• Replication Fork: The Y-shaped region where DNA strands are separated for replication.

• Template Strand: The original strand of DNA used as a template for synthesizing a new complementary strand.

• DNA Polymerase: The enzyme that synthesizes new DNA strands by adding nucleotides to the growing chain.

• Leading Strand: The DNA strand that is synthesized continuously toward the replication fork.

• Lagging Strand: The DNA strand that is synthesized discontinuously in fragments away from the replication fork.

• Okazaki Fragments: Short DNA fragments formed on the lagging strand during replication.

Key Concepts:

1. Base Pairing: Purines (A, G) always pair with pyrimidines (T, C).

2. Semi-conservative Replication: After replication, each daughter molecule has one old (parental) strand and one new (daughter) strand.

3. Direction of Replication: DNA replication occurs in the 5′ to 3′ direction.

4. Leading and Lagging Strands: DNA replication occurs continuously on the leading strand and discontinuously on the lagging strand.

5. DNA Proofreading and Repair: Errors in replication are corrected by proofreading enzymes and repair mechanisms.

6. Telomeres: Repetitive sequences at the ends of chromosomes that protect the DNA from degradation.

DNA Replication Overview:

• Complementary Strands: In DNA replication, each strand acts as a template for the synthesis of a complementary strand.

• Parental Molecule: The original DNA molecule that is unwound to serve as a template for the new strands.

• Base Pairing: Nucleotides are added to the new strand following the base-pairing rules: A pairs with T, and C pairs with G.

Starting DNA Replication:

• Origins of Replication: Replication begins at specific regions called origins of replication, where the DNA strands are separated to form a replication bubble.

• Eukaryotic Chromosomes: These may have hundreds or thousands of origins of replication.

• Replication Fork: The Y-shaped structure where the DNA is actively unwound and new strands are synthesized.

• Bi-directional Replication: Replication proceeds in both directions from each origin of replication.

Enzymes Involved in DNA Replication:

• Helicase: Unwinds the DNA double helix at the replication fork.

• Single-Strand Binding Proteins (SSBs): Bind to and stabilize the single-stranded DNA to prevent it from re-annealing.

• Topoisomerase: Prevents DNA from supercoiling ahead of the replication fork by creating temporary breaks in the DNA and rejoining them.

• Primase: Synthesizes short RNA primers that are necessary for the initiation of DNA synthesis.

• DNA Polymerase: Catalyzes the addition of nucleotides to the growing DNA strand. It can only add nucleotides to an existing 3′ end (hence the need for a primer).

  • DNA Polymerase III: Main enzyme for synthesizing the leading strand.

  • DNA Polymerase I: Replaces RNA primers with DNA nucleotides.

  • DNA Ligase: Joins Okazaki fragments on the lagging strand to form a continuous strand.

DNA Synthesis Process:

• Leading Strand:

  • Synthesized continuously in the 5′ to 3′ direction.

  • DNA polymerase moves toward the replication fork and adds nucleotides continuously.

• Lagging Strand:

  • Synthesized discontinuously as Okazaki fragments in the 5′ to 3′ direction, but away from the replication fork.

  • Each fragment begins with an RNA primer synthesized by primase, followed by DNA polymerase adding nucleotides.

• Okazaki Fragments:

  • Short segments of DNA on the lagging strand.

  • DNA polymerase I removes the RNA primer and replaces it with DNA.

  • DNA ligase connects the Okazaki fragments into a continuous strand.

Proofreading and Repairing DNA:

• DNA Polymerase Proofreading:

  • DNA polymerase has a proofreading function that checks and corrects mismatched base pairs as the DNA is synthesized.

• Mismatch Repair:

  • After DNA replication, mismatched nucleotides may be corrected by repair enzymes that recognize and correct errors in base pairing.

• DNA Damage:

  • DNA can be damaged by physical or chemical agents (e.g., UV radiation, cigarette smoke, X-rays) or undergo spontaneous mutations.

• Nucleotide Excision Repair:

  • Damaged sections of DNA are recognized, cut out by nucleases, and replaced with the correct nucleotides by DNA polymerase and DNA ligase.

Summary of Key Steps in DNA Replication:

1. Initiation:

   • Replication begins at origins of replication. Helicase unwinds the DNA, and single-strand binding proteins stabilize the single strands.

2. Elongation:

   • Leading strand is synthesized continuously by DNA polymerase in the 5′ to 3′ direction.

   • Lagging strand is synthesized in short fragments (Okazaki fragments) due to its opposite direction of synthesis.

3. Replacement of RNA Primer:

   • DNA polymerase I replaces RNA primers with DNA, and DNA ligase connects the Okazaki fragments.

4. Proofreading and Repair:

   • DNA polymerase proofreads the newly synthesized DNA.

   • Mismatch repair and nucleotide excision repair mechanisms fix any errors or damage.

This concludes an overview of DNA replication and repair, highlighting key enzymes, processes, and repair mechanisms that maintain the integrity of the genome.

Lecture 15: Transcription

Dr. Kim Green
Bio 93

Vocabulary:

• Telomeres: Repetitive DNA sequences at the ends of chromosomes that protect them from degradation and prevent loss of important genetic information during replication.

• Telomerase: An enzyme that extends telomeres in germ cells and some somatic cells, helping prevent telomere shortening with each cell division.

• Gene Expression: The process by which the information in a gene is used to produce a functional product, typically a protein.

• Transcription: The process by which an RNA molecule is synthesized from a DNA template.

• Translation: The process by which the mRNA sequence is used to build a polypeptide (protein) at the ribosome.

• RNA Types:

  • mRNA (messenger RNA): Carries the genetic information from the DNA to the ribosome for protein synthesis.

  • tRNA (transfer RNA): Transfers amino acids to the ribosome during translation.

  • rRNA (ribosomal RNA): Part of the ribosome structure and plays a role in protein synthesis.

• Ribosomes: Cellular machinery responsible for translating mRNA into protein.

• Polyribosomes: Multiple ribosomes translating a single mRNA strand simultaneously.

• Primary Transcript: The initial RNA molecule that is synthesized directly from a DNA template (pre-mRNA before processing).

• Codon: A sequence of three nucleotide bases in mRNA that codes for a specific amino acid.

• Template Strand: The strand of DNA that is used as a template for RNA synthesis.

• Reading Frame: The grouping of mRNA codons into sets of three nucleotides, determining the sequence of amino acids in a protein.

• RNA Polymerase: The enzyme that synthesizes RNA by reading the DNA template strand.

• Promoter: A DNA sequence where RNA polymerase binds to initiate transcription.

• Terminator: A DNA sequence that signals the end of transcription.

• Transcription Unit: The stretch of DNA that is transcribed into RNA.

• Transcription Factor: Proteins that help initiate and regulate the process of transcription by assisting RNA polymerase binding.

• TATA Box: A DNA sequence found in many eukaryotic promoters that helps in the binding of transcription factors and RNA polymerase.

• Poly-A Tail: A sequence of adenine nucleotides added to the 3′ end of eukaryotic mRNA to protect it from degradation and aid in transport from the nucleus.

Key Concepts:

1. From Genotype to Phenotype:

   • Genotype refers to an organism’s genetic makeup (DNA sequence), which is transcribed into RNA and translated into proteins.

   • Phenotype is the organism’s observable characteristics, which are determined by the proteins expressed.

2. Gene Expression:

   • Gene expression involves two key processes: transcription (DNA to RNA) and translation (RNA to protein).

   • The central dogma of molecular biology is:
     DNA → RNA → Protein

3. The Role of RNA:

   • mRNA carries the genetic code from DNA to the ribosomes for translation.

   • tRNA and rRNA play roles in translating the mRNA sequence into a functional protein.

4. Transcription:

   • Transcription is the process of copying a segment of DNA into RNA. It occurs in three stages:

     • Initiation: RNA polymerase binds to the promoter and begins transcription.

     • Elongation: RNA polymerase synthesizes the RNA strand by adding nucleotides.

     • Termination: RNA polymerase releases the RNA when it reaches a terminator sequence.

The Process of Transcription:

1. Initiation:

   • Transcription starts when RNA polymerase binds to the promoter region of the DNA.

   • In eukaryotes, the TATA box within the promoter sequence helps RNA polymerase and other transcription factors to bind to the DNA.

   • The transcription initiation complex forms when RNA polymerase and transcription factors assemble at the promoter.

2. Elongation:

   • RNA polymerase moves along the template strand of DNA, unwinding the double helix ahead of it and adding complementary RNA nucleotides to the growing RNA chain.

   • RNA synthesis follows the base-pairing rules:

     • Adenine (A) pairs with uracil (U) in RNA (instead of thymine in DNA).

     • Cytosine (C) pairs with guanine (G), and guanine pairs with cytosine.

   • Transcription progresses at a rate of about 40 nucleotides per second in eukaryotes.

   • Multiple RNA polymerases can transcribe a gene simultaneously.

3. Termination:

   • In eukaryotes, transcription ends when the RNA polymerase continues transcribing past the cleavage site of the pre-mRNA.

   • The RNA is cleaved from the DNA template, and the RNA polymerase detaches, completing the transcription process.

RNA Processing in Eukaryotes:

• Pre-mRNA undergoes modifications before it becomes mature mRNA:

  1. 5′ Cap: A modified guanine nucleotide is added to the 5′ end of the mRNA, which protects the mRNA from degradation and helps it bind to the ribosome for translation.

  2. Poly-A Tail: A string of adenine nucleotides is added to the 3′ end, stabilizing the mRNA and aiding its export from the nucleus.

  3. Splicing: Introns (non-coding regions) are removed from the pre-mRNA, and exons (coding regions) are joined together to form the mature mRNA.

The Genetic Code:

• The genetic code is a set of rules by which the information encoded in mRNA is translated into a sequence of amino acids in a protein.

• The code is read in triplets of nucleotides, known as codons.

• Each codon specifies one amino acid, and the sequence of codons in mRNA determines the amino acid sequence of the protein.

  • 61 codons code for amino acids.

  • 3 codons are stop signals that signal the end of translation.

• The genetic code is redundant but not ambiguous, meaning multiple codons can specify the same amino acid but each codon specifies only one amino acid.

Evolution of the Genetic Code:

• The genetic code is nearly universal across all organisms, from bacteria to humans.

• This universality supports the idea that all life shares a common ancestry.

• Genes from one species can be transplanted into another and can be successfully transcribed and translated to produce functional proteins (e.g., a pig expressing a jellyfish gene).

Summary of Key Points:

• Transcription is the first step in gene expression, where the information in DNA is copied into RNA.

• The process involves three stages: initiation, elongation, and termination.

• The RNA molecule is processed in eukaryotes before being translated into protein.

• The genetic code is read in triplets (codons) and specifies the amino acid sequence of a protein.

• Transcription in eukaryotes occurs in the nucleus, while translation occurs in the cytoplasm at the ribosomes.

This lecture provides the foundational concepts for understanding how genetic information flows from DNA to RNA to protein, crucial for cellular function and organismal traits.

Lecture 16: Translation - Dr. Kim Green, Bio 93

Key Vocabulary:

• RNA Splicing: Process of removing introns and joining exons to produce a mature mRNA.

• Exons + Introns: Exons are coding regions of RNA that remain in mRNA after splicing, while introns are noncoding regions that are removed.

• Translation: The process by which mRNA is translated into a sequence of amino acids to form a protein.

• RNA (mRNA, tRNA, rRNA):

  • mRNA: Messenger RNA, carries genetic information from DNA to the ribosome for protein synthesis.

  • tRNA: Transfer RNA, delivers amino acids to the ribosome during translation.

  • rRNA: Ribosomal RNA, makes up part of the ribosome and helps catalyze protein synthesis.

• Ribosomes + Polyribosomes:

  • Ribosomes: Cellular machinery where translation occurs, consisting of large and small subunits.

  • Polyribosomes: A cluster of ribosomes translating a single mRNA molecule simultaneously, speeding up protein synthesis.

• Codon (triplet code): A sequence of three nucleotides on mRNA that codes for a specific amino acid.

• Anti-codon: A sequence of three bases on tRNA that pairs with a complementary codon on mRNA.

• Aminoacyl-tRNA synthetase: Enzyme that attaches the appropriate amino acid to its corresponding tRNA.

• Signal peptide sequence: A short peptide that directs the nascent protein to a specific location in the cell.

• Mutations: Changes in the DNA sequence, which can affect the resulting protein.

Concepts:

• RNA Splicing:

  • Splicing involves the removal of introns (noncoding regions) and joining of exons (coding regions) in pre-mRNA, resulting in a continuous coding sequence for translation.

• Translation Process:

  • Translation is the synthesis of proteins based on the sequence of codons in mRNA. It occurs in the ribosome, where tRNA brings in amino acids that are assembled into a protein chain.

  • Targeting proteins: After translation, proteins are often targeted to specific cellular locations based on sequences such as the signal peptide.

Modification of RNA Transcripts:

• RNA Processing:

  • Eukaryotic cells modify pre-mRNA in the nucleus before exporting it to the cytoplasm.

  • This processing includes adding a 5' cap (modified nucleotide) and a 3' poly-A tail, which protect mRNA from degradation, facilitate export from the nucleus, and aid in translation initiation.

  • Introns are removed, and exons are spliced together to form the final mRNA.

RNA Splicing and Spliceosomes:

• Spliceosomes are complexes of proteins and small nuclear RNAs (snRNAs) that recognize splice sites and catalyze the removal of introns and joining of exons.

Molecular Components of Translation:

• tRNA:

  • tRNA molecules carry specific amino acids to the ribosome.

  • Each tRNA has an anticodon that pairs with the complementary codon on mRNA.

  • Aminoacyl-tRNA synthetase catalyzes the attachment of amino acids to their corresponding tRNAs.

Ribosomes and Polyribosomes:

• Ribosomes facilitate the matching of tRNA anticodons with mRNA codons, enabling protein synthesis.

• A polyribosome is a cluster of multiple ribosomes translating the same mRNA, allowing rapid production of protein molecules.

Stages of Translation:

1. Initiation:

   • The ribosome assembles around the mRNA and the first tRNA molecule, starting at the start codon (usually AUG).

   • This step requires GTP for energy.

2. Elongation:

   • Involves three steps:

     1. Codon recognition: tRNA anticodon binds to the mRNA codon.

     2. Peptide bond formation: The ribosome catalyzes the bond between amino acids.

     3. Translocation: The ribosome moves along the mRNA, and the tRNA in the P site is moved to the E site for exit.

3. Termination:

   • Translation stops when a stop codon (UAG, UAA, or UGA) enters the A site.

   • A release factor binds, causing the polypeptide chain to be released.

Mutations and Their Effects on Translation:

• Point Mutations: Changes in a single base pair, which can affect protein structure and function.

  • Silent mutations: No effect on the amino acid due to redundancy in the genetic code.

  • Missense mutations: Code for the wrong amino acid, possibly affecting protein function.

  • Nonsense mutations: Change a codon to a stop codon, producing a truncated and nonfunctional protein.

• Insertions and Deletions: Add or remove nucleotides, potentially causing frameshift mutations, where the reading frame is altered, leading to incorrect protein sequences.

Polyribosomes:

• Polyribosomes allow multiple ribosomes to translate a single mRNA molecule at the same time, increasing the efficiency of protein synthesis.

Summary of Translation and Mutations:

• Translation is a crucial step in converting genetic information into functional proteins. Mutations, especially in the coding sequence, can disrupt protein structure and function, leading to diseases like sickle-cell anemia.

Lecture 16: Translation - Dr. Kim Green, Bio 93

Key Vocabulary:

• RNA Splicing: Process of removing introns and joining exons to produce a mature mRNA.

• Exons + Introns: Exons are coding regions of RNA that remain in mRNA after splicing, while introns are noncoding regions that are removed.

• Translation: The process by which mRNA is translated into a sequence of amino acids to form a protein.

• RNA (mRNA, tRNA, rRNA):

  • mRNA: Messenger RNA, carries genetic information from DNA to the ribosome for protein synthesis.

  • tRNA: Transfer RNA, delivers amino acids to the ribosome during translation.

  • rRNA: Ribosomal RNA, makes up part of the ribosome and helps catalyze protein synthesis.

• Ribosomes + Polyribosomes:

  • Ribosomes: Cellular machinery where translation occurs, consisting of large and small subunits.

  • Polyribosomes: A cluster of ribosomes translating a single mRNA molecule simultaneously, speeding up protein synthesis.

• Codon (triplet code): A sequence of three nucleotides on mRNA that codes for a specific amino acid.

• Anti-codon: A sequence of three bases on tRNA that pairs with a complementary codon on mRNA.

• Aminoacyl-tRNA synthetase: Enzyme that attaches the appropriate amino acid to its corresponding tRNA.

• Signal peptide sequence: A short peptide that directs the nascent protein to a specific location in the cell.

• Mutations: Changes in the DNA sequence, which can affect the resulting protein.

Concepts:

• RNA Splicing:

  • Splicing involves the removal of introns (noncoding regions) and joining of exons (coding regions) in pre-mRNA, resulting in a continuous coding sequence for translation.

• Translation Process:

  • Translation is the synthesis of proteins based on the sequence of codons in mRNA. It occurs in the ribosome, where tRNA brings in amino acids that are assembled into a protein chain.

  • Targeting proteins: After translation, proteins are often targeted to specific cellular locations based on sequences such as the signal peptide.

Modification of RNA Transcripts:

• RNA Processing:

  • Eukaryotic cells modify pre-mRNA in the nucleus before exporting it to the cytoplasm.

  • This processing includes adding a 5' cap (modified nucleotide) and a 3' poly-A tail, which protect mRNA from degradation, facilitate export from the nucleus, and aid in translation initiation.

  • Introns are removed, and exons are spliced together to form the final mRNA.

RNA Splicing and Spliceosomes:

• Spliceosomes are complexes of proteins and small nuclear RNAs (snRNAs) that recognize splice sites and catalyze the removal of introns and joining of exons.

Molecular Components of Translation:

• tRNA:

  • tRNA molecules carry specific amino acids to the ribosome.

  • Each tRNA has an anticodon that pairs with the complementary codon on mRNA.

  • Aminoacyl-tRNA synthetase catalyzes the attachment of amino acids to their corresponding tRNAs.

Ribosomes and Polyribosomes:

• Ribosomes facilitate the matching of tRNA anticodons with mRNA codons, enabling protein synthesis.

• A polyribosome is a cluster of multiple ribosomes translating the same mRNA, allowing rapid production of protein molecules.

Stages of Translation:

1. Initiation:

   • The ribosome assembles around the mRNA and the first tRNA molecule, starting at the start codon (usually AUG).

   • This step requires GTP for energy.

2. Elongation:

   • Involves three steps:

     1. Codon recognition: tRNA anticodon binds to the mRNA codon.

     2. Peptide bond formation: The ribosome catalyzes the bond between amino acids.

     3. Translocation: The ribosome moves along the mRNA, and the tRNA in the P site is moved to the E site for exit.

3. Termination:

   • Translation stops when a stop codon (UAG, UAA, or UGA) enters the A site.

   • A release factor binds, causing the polypeptide chain to be released.

Mutations and Their Effects on Translation:

• Point Mutations: Changes in a single base pair, which can affect protein structure and function.

  • Silent mutations: No effect on the amino acid due to redundancy in the genetic code.

  • Missense mutations: Code for the wrong amino acid, possibly affecting protein function.

  • Nonsense mutations: Change a codon to a stop codon, producing a truncated and nonfunctional protein.

• Insertions and Deletions: Add or remove nucleotides, potentially causing frameshift mutations, where the reading frame is altered, leading to incorrect protein sequences.

Polyribosomes:

• Polyribosomes allow multiple ribosomes to translate a single mRNA molecule at the same time, increasing the efficiency of protein synthesis.

Summary of Translation and Mutations:

• Translation is a crucial step in converting genetic information into functional proteins. Mutations, especially in the coding sequence, can disrupt protein structure and function, leading to diseases like sickle-cell anemia.

Lecture 17: Dividing the Cell I: Cell Cycle and Mitosis

Key Vocabulary

• Cell Division: The process by which a parent cell divides to produce two or more daughter cells. It is essential for growth, reproduction, and tissue repair in organisms.

• Mitotic Spindle: A structure made of microtubules that segregates chromosomes during mitosis. It ensures that each daughter cell receives the correct number of chromosomes.

• Stem Cells: Undifferentiated cells that have the ability to develop into various types of specialized cells. They are essential for growth, development, and repair of tissues.

• Centrosome: A region of the cell that organizes microtubules and is important for the formation of the mitotic spindle during cell division. It contains a pair of centrioles in animal cells.

• Cell Cycle: The series of events that take place in a cell leading to its division and replication. It consists of Interphase (G1, S, G2 phases) and Mitotic Phase (Mitosis and Cytokinesis).

• Centromere: The region of a chromosome where the sister chromatids are joined together. It is the attachment site for the mitotic spindle fibers during cell division.

• Mitosis: The phase of the cell cycle where the nucleus divides into two genetically identical nuclei. Mitosis is divided into four phases: prophase, metaphase, anaphase, and telophase.

• Nuclear Envelope: A double membrane that surrounds the nucleus in eukaryotic cells. It separates the cell’s genetic material from the cytoplasm and disassembles during mitosis.

• Interphase: The phase of the cell cycle where the cell grows, develops, and prepares for division. It consists of three subphases: G1 (cell growth), S (DNA replication), and G2 (final preparations for mitosis).

• Kinetochore: A protein structure on the centromere where spindle fibers attach during mitosis. It plays a crucial role in chromosome movement.

• Mitotic Phase: The phase of the cell cycle during which mitosis (nuclear division) and cytokinesis (cytoplasmic division) occur. This phase results in two genetically identical daughter cells.

• Chromosome: A structure made of DNA and proteins that carries genetic information. Chromosomes are replicated during the S phase of interphase and are condensed during mitosis.

• Microtubule: A type of protein filament that forms part of the cytoskeleton and is involved in cell shape, motility, and chromosome movement during cell division.

• Sister Chromatids: Two identical copies of a chromosome formed during DNA replication in the S phase. They are joined together at the centromere and separated during mitosis.

• Cytokinesis: The final step in cell division, where the cytoplasm divides and two daughter cells are formed. It usually occurs after mitosis is complete.

• Cohesin: A protein complex that holds sister chromatids together after DNA replication. It is crucial for chromosome alignment and separation during mitosis.

Learning Outcomes

1. Describe the events in the cell cycle, including mitosis, and how chromosomes, the spindle apparatus (microtubules), and nuclear envelope change at each stage.

2. Understand how mutations in the spindle apparatus may cause developmental disorders.

3. Learn how anti-cancer drugs can stop uncontrolled cell division.

4. Analyze and interpret data from histograms.

Importance of Cell Division

• Reproduction: In single-celled organisms like amoeba, cell division is how reproduction occurs.

• Tissue Renewal: Cell division is essential for the replacement and repair of cells.

• Growth and Development: For example, from one cell, an organism grows into 200 trillion cells.

Stem Cells

• Used in tissue development and disease modeling.

• Important for testing drugs, developing therapies, and generating specialized cells for cell-based therapies.

Math Problem: Red Blood Cell (RBC) Lifespan

• RBC lifespan is 120 days.

• If the body has 5 liters of blood, each microliter containing 5 million RBCs, how many RBCs must be produced per second to replace them?

• This demonstrates the rapid and continuous need for cell division.

Key Concept: Genetic Material

• Identical genetic material must be passed from the parent cell to offspring cells.

• This is achieved through cell cycle regulation and mitosis.

The Cell Cycle

1. Interphase: The cell is growing and preparing for division. It has three phases:

   • G1 (Gap 1): Synthesis of macromolecules and organelles.

   • S (Synthesis): DNA replication.

   • G2 (Gap 2): Final preparations for mitosis.

2. Mitotic Phase: This phase involves mitosis (division of the nucleus) and cytokinesis (division of the cytoplasm).

   • Mitosis: Consists of five subphases.

   • Cytokinesis: The division of the cytoplasm into two daughter cells.

Chromosome Structure

• A chromosome is a single molecule of DNA.

• During S phase, DNA is replicated.

• After replication, chromosomes consist of two identical sister chromatids joined by a centromere.

Stages of Mitotic Cell Division

• Prophase: Chromosomes condense, and the mitotic spindle starts to form.

• Prometaphase: The nuclear envelope breaks down, and spindle fibers attach to the chromosomes.

• Metaphase: Chromosomes align along the metaphase plate.

• Anaphase: Sister chromatids separate and move to opposite poles.

• Telophase: The nuclear envelope re-forms around the chromosomes, and the cell starts to divide.

Chromosome Movement

• In anaphase, chromosomes are pulled apart via kinetochore microtubules.

• Motor proteins help chromosomes "walk" along microtubules.

• Experiment with fluorescent labeling shows that the microtubules shorten at the kinetochore during chromosome movement.

Mutations Leading to Disorders

• Spindle Defects: Mutations in genes related to the mitotic spindle or centrosomes can cause brain disorders like:

  • Microcephaly: Small brain with fewer neurons.

  • Lissencephaly: Smooth brain surface.

• These disorders are linked to genes involved in microtubule stability or centrosome function.

Cytokinesis: Division of the Cytoplasm

• In animal cells, cytokinesis is achieved through a cleavage furrow.

• In plant cells, a cell plate forms to divide the cytoplasm.

Scientific Method

• Hypothesis: A testable explanation for observations.

  • Example: A hypothesis that a drug, 93stop, will stop cell proliferation at a certain stage of the cell cycle.

• Experimental Design:

  • Control Group: Cells not treated with the drug.

  • Test Group: Cells treated with 93stop.

  • After 72 hours, DNA is stained to assess which phase of the cell cycle cells are in.

Flow Cytometry and Data Analysis

• Flow Cytometry is used to measure fluorescence in cells, revealing which cell cycle phase they are in.

• Histogram: Data is presented in histograms to show the distribution of cells in different phases.

Cancer Therapeutic Analysis

• Data from a control group and test group shows how 93stop affects cell cycle progression.

• Histogram Analysis: The amount of fluorescence per cell helps determine if and where 93stop halts cell proliferation.

Conclusion

• The experiment and data analysis provide insights into how the therapeutic drug impacts cell division, potentially providing a mechanism for targeting cancer cells.

Next Steps

• Continue analyzing data, including interpreting histograms and discussing the impact of treatments on cell cycle regulation.

This lecture provides a comprehensive overview of the cell cycle and mitosis, emphasizing the role of precise cell division in both normal and abnormal cell growth.

Lecture 18: Dividing the Cell II: Cell Cycle Regulation, Cancer

Dr. Ian F. Smith, Bio93

Vocabulary Definitions

1. Checkpoints: Critical control points in the cell cycle where the cell checks for conditions such as DNA damage or incomplete cell division. If conditions are not right, the cell cycle is halted.

2. Cyclin-dependent protein kinase (Cdk): A protein kinase that regulates the cell cycle. It requires binding to a cyclin to be activated. Cdk activity helps control progression through various checkpoints in the cell cycle.

3. Growth Factor: External signals that stimulate cell division. They bind to receptors on the cell surface and activate intracellular signaling pathways to promote the cell cycle.

4. Anchorage Dependence: A property of normal cells where they require attachment to a surface (such as the extracellular matrix) to divide. Lack of anchorage can prevent cell division.

5. Density-dependent Inhibition: A mechanism in which crowded cells stop dividing when they come into contact with each other. This is a normal regulatory feature of most cells to prevent over-proliferation.

6. Proto-oncogene: A normal gene that codes for a protein involved in stimulating cell growth and division. If mutated or overexpressed, it can become an oncogene, potentially leading to cancer.

7. Oncogene: A mutated or overactive proto-oncogene that can lead to uncontrolled cell division, contributing to the development of cancer.

8. Tumor Suppressor Gene: Genes that inhibit cell division or promote cell death (apoptosis). Mutations in these genes that inactivate them can lead to cancer.

9. p53: A tumor suppressor gene known as the "guardian of the genome." It regulates the cell cycle and prevents the proliferation of damaged cells. Mutations in p53 are common in many cancers.

Learning Outcomes

• Understand how cell cycle checkpoints function.

• Describe how cyclins regulate the cell cycle.

• Explain the role of oncogenes and tumor suppressor genes in cancer development.

• Interpret data from histograms, such as the effect of a drug on the cell cycle.

Key Concepts and Details

Scientific Experiment and Data Analysis

• Experiment: The drug '93stop' is tested on human brain cancer cells to see how it affects the cell cycle. Cells are treated for 72 hours, and DNA is stained to track the cell cycle stages (G1, S, G2).

• Interpretation: Data suggests that '93stop' halts the cell cycle, particularly at the G1 checkpoint. This suggests that it could be an effective drug to stop cancer cell proliferation.

Cell Cycle Control Mechanisms

• Checkpoints:

  • G1 checkpoint: Determines whether a cell will proceed to the S phase. If conditions are not favorable (e.g., DNA damage), the cell enters a non-dividing state called G0.

  • G2 and M checkpoints: Ensure proper chromosome replication and segregation during cell division.

• Cyclin-dependent Kinases (Cdk):

  • Cdk must bind to a cyclin to become active.

  • MPF (Maturation Promoting Factor): The combination of cyclin and Cdk that regulates the transition from G2 to M phase, promoting mitosis.

• Cyclin Fluctuations: Cyclin levels rise and fall in a cyclic manner during the cell cycle, influencing the activation of Cdk and thus regulating the cell cycle progression.

Growth Signals and Cancer Development

• Growth Factors: For cells to divide, they must receive external signals. For example, the platelet-derived growth factor (PDGF) stimulates cell division when needed.

• Anchorage Dependence and Density-dependent Inhibition: These are mechanisms that prevent overgrowth of cells, ensuring that cells grow only when necessary.

Cancer: Loss of Regulation

• Cancer Cells: Cancer cells escape normal regulatory mechanisms, leading to uncontrolled cell division. They can ignore signals that would normally stop cell division, such as growth factors or cell contact inhibition.

• Metastasis: Cancer cells can spread to other parts of the body via blood or lymphatic vessels, forming new tumors in distant tissues.

Key Genes in Cancer

• Proto-oncogenes: Normal genes involved in stimulating cell division. They can become oncogenes if mutated or overexpressed, leading to cancerous cell growth.

  • Example: Ras gene mutation can cause the Ras protein to remain active, continuously signaling the cell to divide.

• Tumor Suppressor Genes: These genes inhibit cell division or promote apoptosis. Loss of function in these genes leads to unchecked cell division.

  • Example: p53 is a key tumor suppressor gene. It regulates cell cycle checkpoints and induces apoptosis in damaged cells. Mutations in p53 are commonly found in cancer cells.

Cancer Development Mechanisms

1. Proto-oncogene to Oncogene Conversion:

   • Mutations in proto-oncogenes, such as Ras, can cause them to become hyperactive, leading to continuous cell division.

2. Loss of Tumor Suppressor Genes:

   • When tumor suppressor genes like p53 are mutated, the brakes on the cell cycle are removed, and damaged cells continue to divide, leading to cancer.

3. Multistep Model of Cancer: Cancer development often involves the accumulation of mutations in multiple genes, including both proto-oncogenes and tumor suppressor genes. This is why cancer is more common with age.

Peto's Paradox

• Despite larger animals having more cells and more opportunities for mutations, they do not have higher rates of cancer. This phenomenon is called Peto's Paradox. Researchers are still investigating why larger animals like elephants have fewer cancer cases despite their size.

Conclusion and Application of Knowledge

• Understanding the regulation of the cell cycle, the role of checkpoints, and the involvement of oncogenes and tumor suppressor genes is crucial for understanding how cancer develops.

• Cancer treatments: Drugs like '93stop' that target specific stages in the cell cycle can be used to stop cancer cell proliferation.

These notes cover the regulation of the cell cycle, the mechanisms leading to cancer, and the roles of different genes in cell division and cancer development. The lecture also integrates experimental design and interpretation of data in the context of understanding cancer therapies.

Lecture 19: Dividing the Cell III: Meiosis and Genetic Variation

Dr. Ian F. Smith, Bio93

Vocabulary Definitions

1. Meiosis: A type of cell division that reduces chromosome number by half, producing four non-identical haploid gametes (sperm and egg cells) for sexual reproduction.

2. Trisomy: A condition in which an individual has three copies of a particular chromosome, instead of the usual two. It often leads to genetic disorders such as Down Syndrome (Trisomy 21).

3. Diploid (2n): A cell that contains two complete sets of chromosomes, one from each parent (e.g., somatic cells in humans with 46 chromosomes, 23 pairs).

4. Independent Assortment: The random distribution of homologous chromosomes during meiosis, which increases genetic diversity. This occurs during metaphase I.

5. Haploid (n): A cell that contains one complete set of chromosomes, half the number of a diploid cell (e.g., gametes with 23 chromosomes in humans).

6. Gametes: Reproductive cells (sperm and egg) that are haploid and combine during fertilization to form a diploid zygote.

7. Genetic Variability: The variety of genetic information present in a population, which results from processes like crossing over, independent assortment, and random fertilization.

8. Karyotype: A visual representation of the chromosomes in a cell, arranged in pairs, used to identify chromosomal abnormalities.

9. Crossing Over: The exchange of genetic material between homologous chromosomes during meiosis I, which creates new combinations of alleles and increases genetic diversity.

10. Homologous Chromosomes: Chromosomes that are similar in shape, size, and genetic content, with one inherited from each parent.

11. Sister Chromatids: Identical copies of a chromosome, formed by DNA replication, that are connected at the centromere and separated during meiosis II.

12. Non-sister Chromatids: Chromatids from different homologous chromosomes that pair up and exchange genetic material during crossing over in meiosis I.

13. Non-disjunction: A failure of homologous chromosomes or sister chromatids to separate properly during meiosis, leading to an abnormal number of chromosomes in the resulting gametes.

Learning Outcomes

• Understand how karyotypes provide insights into chromosomal structure and abnormalities.

• Explain the purpose of meiosis and the difference between diploid and haploid cells.

• Describe each step of meiosis and how it reduces chromosome number.

• Predict how abnormal chromosome numbers (e.g., non-disjunction) or structural chromosome changes can lead to disorders.

• Understand how meiosis contributes to genetic variation.

Key Concepts and Details

Human Life Cycle and Meiosis

• Meiosis is the process by which gametes (sperm and egg cells) are produced. It reduces the chromosome number from diploid (2n) to haploid (n).

  • Gametes (sperm and egg): Haploid cells, each with 23 chromosomes.

  • Fertilization: The fusion of two haploid gametes to form a diploid zygote with 46 chromosomes.

• Diploid (2n): A zygote or somatic cell that contains two sets of chromosomes, one from each parent.

• Haploid (n): Gametes, which have only one set of chromosomes (23 chromosomes in humans).

Meiosis Overview

• Meiosis I: Homologous chromosomes are separated, reducing chromosome number by half.

• Meiosis II: Sister chromatids are separated, similar to mitosis, resulting in four haploid daughter cells.

Karyotype

• A karyotype is an organized arrangement of an individual's chromosomes, typically shown in pairs, used to study chromosomal abnormalities.

  • How to prepare: Cells are arrested in metaphase (where chromosomes are condensed and visible) using a hypotonic solution that causes cells to swell.

  • In humans, there are 46 chromosomes, arranged into 23 pairs of homologous chromosomes.

Meiosis vs. Mitosis

• Mitosis:

  • Results in two identical diploid daughter cells.

  • Used for growth, repair, and asexual reproduction.

  • No genetic variation (identical clones).

• Meiosis:

  • Reduces chromosome number by half, producing four non-identical haploid gametes.

  • Increases genetic diversity via processes like crossing over and independent assortment.

Chromosome Abnormalities

• Non-disjunction: When chromosomes fail to separate properly during meiosis, leading to an abnormal number of chromosomes in the gametes.

  • Trisomy 21 (Down Syndrome): A result of non-disjunction where chromosome 21 is present in three copies instead of two.

Mechanisms Contributing to Genetic Variation

1. Crossing Over: During meiosis I, homologous chromosomes exchange genetic material, leading to new combinations of alleles on the chromosomes.

2. Independent Assortment: The random alignment of homologous chromosomes during metaphase I results in different combinations of maternal and paternal chromosomes in the gametes. In humans, this can produce over 8 million different combinations of chromosomes in the gametes.

3. Random Fertilization: The fusion of any sperm and egg from a population creates an immense number of genetic combinations. In humans, this can result in over 70 trillion possible genetic combinations when considering the variation in both sperm and egg.

Important Terminology and Key Events in Meiosis

• Diploid cell (2n): A cell with two sets of chromosomes (one from each parent).

• Haploid cell (n): A cell with one set of chromosomes (half the chromosome number of a diploid cell).

• Gametes: Haploid cells (sperm and egg) produced by meiosis.

• Karyotype: A display of chromosomes used to identify chromosomal abnormalities.

Stages of Meiosis

1. Meiosis I:

   • Homologous chromosomes are separated, reducing the chromosome number from diploid (2n) to haploid (n).

   • Crossing over occurs in prophase I, creating genetic diversity.

2. Meiosis II:

   • Sister chromatids (which are identical copies of chromosomes) are separated.

   • This stage is similar to mitosis, but the result is haploid daughter cells instead of diploid.

Summary of Key Concepts

• Genetic Variation: Meiosis is crucial for generating genetic diversity, which is essential for evolution and adaptation. It introduces variation through:

  • Crossing over during prophase I.

  • Independent assortment during metaphase I.

  • Random fertilization of gametes.

• Abnormal Chromosome Number: Non-disjunction can lead to disorders like Down Syndrome (Trisomy 21), where an individual has three copies of chromosome 21 instead of two.

These notes summarize the major concepts of meiosis, how it contributes to genetic variation, and the processes that can lead to chromosomal disorders. The key processes of crossing over, independent assortment, and random fertilization all contribute to the diversity seen in offspring from sexual reproduction.

Lecture 20: Genes and Chromosomes I: Mendel and the Gene

Dr. Ian F. Smith, Bio93

Nomenclature

1. Gene: A unit of heredity made of a specific sequence of nucleotides in DNA that codes for a protein or RNA molecule.

2. Genetics: The scientific study of heredity and hereditary variation.

3. Genotype: The genetic composition of an organism (e.g., alleles an organism carries).

4. Phenotype: The observable traits or characteristics of an organism, determined by both genotype and environmental factors.

5. Trait: A specific characteristic of an organism that can vary (e.g., flower color, fur color).

6. Character: An observable feature or trait of an organism (e.g., color, shape).

7. Allele: Different forms of a gene found at the same locus on homologous chromosomes.

8. Dominant Allele: An allele that expresses its phenotype even in the presence of a recessive allele.

9. Recessive Allele: An allele whose phenotype is expressed only when two copies are present (homozygous).

10. Homozygous: An organism with two identical alleles for a particular trait.

11. Heterozygous: An organism with two different alleles for a particular trait.

12. Locus (Loci): The specific physical location of a gene on a chromosome.

13. Punnett Square: A diagram used to predict the genotype and phenotype combinations in a genetic cross.

Learning Outcomes

• Use proper terminology to describe genes, genetics, and inheritance.

• Predict phenotypes and genotypes based on genetic information.

• Explain the molecular basis of dominant and recessive alleles.

• Compare Mendel’s Laws to events occurring in meiosis.

• Use Punnett squares and probability rules to predict offspring traits in monohybrid, dihybrid, and three-character crosses.

Key Definitions and Concepts

1. Genetics: The study of how traits are inherited through generations and the molecular mechanisms behind inheritance.

2. Gene: A segment of DNA that codes for a particular trait or protein.

3. Inheritance: The process of passing genetic information from parents to offspring.

Mendel’s Contributions to Genetics

• Gregor Mendel: Conducted experiments on pea plants in the 1850s, leading to the discovery of the basic principles of heredity. His work established that inheritance is particulate, not blending.

• Model Organisms: Organisms like Drosophila (fruit flies), yeast, and guinea pigs are commonly used in genetics studies due to their short life cycles and ease of breeding.

Mendel’s Experimental Setup

• Mendel studied pea plants with clear, easily distinguishable traits (e.g., flower color, seed shape).

  • Character: Observable, heritable feature (e.g., color).

  • Trait: Variations in a character (e.g., purple or white flowers).

• Mendel chose traits that follow a simple dominant/recessive inheritance pattern, where one allele is dominant over the other.

Blending vs. Particulate Hypothesis

• Blending Hypothesis: Proposed that genetic material from both parents blends together to form the offspring's traits.

• Particulate Hypothesis: Mendel’s theory, stating that parents pass discrete, unblended units (genes) to their offspring, which remain unchanged through generations.

Mendel’s Laws of Heredity

1. Law of Segregation

• Principle: During gamete formation, the two alleles for each character separate (segregate) so that each gamete receives only one allele.

• Example: In pea plants, the allele for flower color (purple or white) separates during meiosis so that each gamete receives only one allele.

  • Mendel’s Results: When a homozygous purple-flowered plant (PP) was crossed with a homozygous white-flowered plant (pp), all F1 offspring had purple flowers. However, in the F2 generation, a 3:1 ratio of purple to white flowers appeared, supporting the Law of Segregation.

2. Law of Independent Assortment

• Principle: Genes for different traits segregate independently of each other during gamete formation (applies to genes on different chromosomes or genes that are far apart on the same chromosome).

• Example: When following two traits (e.g., seed color and seed shape), the inheritance of one does not affect the inheritance of the other.

  • Mendel’s Results: In a dihybrid cross (e.g., YyRr x YyRr), he observed a 9:3:3:1 phenotypic ratio in the F2 generation, supporting the Law of Independent Assortment.

Punnett Square and Probability Rules

Punnett Square: A diagram that helps predict the probability of inheriting certain traits based on parental genotypes.

• Monohybrid Cross: A cross involving one character (e.g., flower color).

• Dihybrid Cross: A cross involving two characters (e.g., flower color and plant height).

  • Example:

    • Parental Genotypes: PP x pp

    • F1 Genotype: All Pp (heterozygous).

    • F2 Generation: When F1 plants are crossed, the offspring will show a 3:1 phenotypic ratio (dominant to recessive).

Test Cross: Used to determine the genotype of an individual with a dominant phenotype by crossing it with a homozygous recessive individual.

• Dominant Phenotype: Could be either homozygous dominant (PP) or heterozygous (Pp).

  • Example: Cross a purple-flowered (P?) plant with a white-flowered (pp) plant. If any white-flowered plants appear, the purple-flowered parent is heterozygous (Pp).

Genetic Problems and Punnett Squares

• Example Problem: Cross a brown fur guinea pig (BB) with an albino guinea pig (bb).

  • F1 Generation: All offspring will be Bb (brown fur).

  • If you cross Bb with bb:

    • The offspring will have a 1/2 chance of being brown (Bb) and a 1/2 chance of being albino (bb).

Probabilities in Genetic Crosses

• Multiplication Rule: The probability of two independent events occurring together is the product of their individual probabilities. For example, the probability of inheriting two recessive alleles (rr) from two heterozygous parents:

  • 1/2 (from one parent) × 1/2 (from the other parent) = 1/4 chance of rr.

• Addition Rule: The probability of one or another event happening is the sum of their individual probabilities. For example, the probability of a Bb offspring from two Bb parents:

  • 1/4 (from first parent) + 1/4 (from second parent) = 1/2 chance of Bb.

Summary of Mendel’s Laws

1. Law of Segregation: Two alleles for each gene segregate into separate gametes during meiosis.

2. Law of Independent Assortment: Genes for different traits segregate independently of each other during meiosis.

These laws are explained by the physical separation of alleles during meiosis, where chromosomes (and their genes) are sorted into gametes.

Mendelian Inheritance Reflects the Rules of Probability

• The inheritance of alleles follows probability rules like coin tosses: each allele has a 50% chance of being inherited from a parent.

• The combination of alleles from both parents creates a range of possible genetic outcomes for offspring.

Lecture 21: Genes and Chromosomes II: Human Genetic Disease

Dr. Ian Smith, Bio93

Nomenclature

• Incomplete dominance: A genetic scenario where neither allele is dominant, resulting in an intermediate phenotype.

• Co-dominance: A situation where both alleles contribute equally to the phenotype.

• Pleiotropy: A single gene influencing multiple phenotypic traits.

• Epistasis: A gene at one locus can mask or alter the expression of a gene at a different locus.

• Polygenic inheritance: A trait influenced by more than one gene, typically resulting in continuous variation.

• CRISPR: A gene-editing technology that allows precise modification of DNA.

• Epigenetics: Changes in gene expression or cellular phenotype that do not involve alterations in the underlying DNA sequence.

Learning Outcomes

• Compare and contrast incomplete dominance, co-dominance, pleiotropy, and polygenic inheritance.

• Understand how epistasis can lead to mismatches between genotype and phenotype.

• Use pedigree analysis to track inheritance patterns of traits and predict offspring characteristics.

• Distinguish between recessively and dominantly inherited traits.

• Understand how epigenetics can integrate environmental factors (e.g., diet) to affect phenotype.

Inheritance Patterns in Humans

While many traits in humans follow Mendelian inheritance patterns, some inheritance patterns are more complex than simple Mendelian genetics. These include:

1. Incomplete dominance

2. Multiple alleles (co-dominance)

3. Pleiotropy

4. Epistasis

5. Polygenic inheritance

6. Environmental impact

Complex Inheritance Patterns

1. Incomplete Dominance

• Example: Flower color in snapdragons

  • A cross between red-flowered (RR) and white-flowered (WW) plants produces all pink (RW) offspring in the F1 generation.

  • In the F2 generation, when F1 plants are self-pollinated, a 1:2:1 phenotypic ratio appears: 25% red, 50% pink, 25% white.

  • Example in humans: Hypercholesterolemia

    • Genotype:

      • HH: Homozygous normal (ability to make LDL receptors)

      • Hh: Heterozygous (mild disease)

      • hh: Homozygous for inability to make LDL receptors (severe disease)

    • Phenotype:

      • HH: Normal cholesterol levels

      • Hh: Mild hypercholesterolemia

      • hh: Severe hypercholesterolemia and potential cardiovascular issues.

2. Co-dominance

• Example: ABO blood group system

  • Alleles: A, B, O

  • If an individual inherits an A allele and a B allele (AB), both A and B antigens are expressed on red blood cells, making the individual AB blood type.

  • Both alleles contribute equally to the phenotype, which is a classic case of co-dominance.

3. Pleiotropy

• Definition: A single gene influences multiple phenotypic traits.

  • Example: Sickle-cell anemia

    • The sickle-cell allele causes deformed red blood cells, which lead to a cascade of health problems, such as pain, stroke, kidney problems, and more.

    • This demonstrates how pleiotropic effects can span various bodily functions.

• CRISPR in Sickle Cell Anemia: Gene-editing technologies like CRISPR/Cas9 are being used to reverse the mutation that causes sickle-cell anemia, which could potentially cure the disease.

4. Epistasis

• Definition: The expression of one gene is affected by another gene at a different locus.

  • Example: Coat color in Labrador Retrievers

    • Gene 1 (E/e): Pigment deposition

      • E (dominant): Allows pigment deposition.

      • e (recessive): No pigment deposited (resulting in a yellow coat).

    • Gene 2 (B/b): Pigment color

      • B (dominant): Black pigment.

      • b (recessive): Brown pigment.

    • The E gene is epistatic to the B gene. If a dog has ee genotype (homozygous recessive), it will have a yellow coat regardless of the B/b genotype.

    • The phenotypic ratio is 9 black, 3 brown, and 4 yellow, due to epistasis.

5. Polygenic Inheritance

• Example: Human skin color

  • Skin color is determined by multiple genes, each contributing a small amount to the overall phenotype.

  • In a cross between two AaBbCc individuals (intermediate skin shade), offspring would exhibit a broad range of skin tones, forming a normal distribution of phenotypes.

6. Environmental Impact

• Many traits are influenced by the environment, which interacts with the genotype to produce a phenotype. This concept is known as the norm of reaction.

  • Example: Human height is influenced by both genetic factors and environmental factors such as nutrition.

  • Example in plants: The color of hydrangeas can change depending on soil pH, which demonstrates how the environment can alter phenotype expression.

Epigenetics

• Definition: Epigenetics involves changes in gene expression or cellular phenotype that do not involve changes to the underlying DNA sequence. It can be influenced by environmental factors like diet, stress, and toxins.

• Gene Regulation: Epigenetic mechanisms include changes in chromatin structure, which turn genes "on" or "off". These changes can be stable and passed to the next generation.

  • Example: Identical twins show different epigenetic tags that change with age and environmental exposures (diet, stress).

• Impact of Diet:

  • Queen bees and worker bees are genetically identical, but their different phenotypes (queen vs. worker) arise from different diets (royal jelly) during development.

  • Example in mice: Pregnant yellow mice fed folic acid have healthy pups, while those fed Bisphenol A (BPA) have pups with abnormalities, demonstrating how diet can influence epigenetics.

Pedigree Analysis

• Pedigrees are diagrams used to trace the inheritance of traits across generations. They are especially useful for tracking genetic disorders.

  • Recessive traits: A recessive trait will only appear in the phenotype when an individual inherits two copies of the recessive allele.

    • Example: Albinism is a recessive trait. A pedigree showing albinism would typically involve two carriers (heterozygous parents) producing albino children.

  • Dominant traits: A dominant trait appears in the phenotype when at least one dominant allele is inherited.

    • Example: Polydactyly, the condition of having extra fingers or toes, is caused by a dominant allele. Even one copy of the dominant allele will result in the expression of this trait.

  • Dominantly Inherited Disorders: Huntington's disease is an example of a dominantly inherited disorder. An individual with one copy of the mutated allele will develop symptoms of Huntington's disease, typically in their 40s or 50s.

X-Linked Traits: Color Blindness

• Color blindness is more common in males than females because the gene for color vision is located on the X chromosome.

  • Females have two X chromosomes, so they need two copies of the mutated gene (one on each X) to express color blindness.

  • Males only have one X chromosome, so if they inherit the mutated gene on their X chromosome, they will express color blindness.

Summary of Key Concepts

• Incomplete dominance: Intermediate phenotype (e.g., pink flowers from red and white parents).

• Co-dominance: Both alleles contribute equally to phenotype (e.g., AB blood type).

• Pleiotropy: One gene affects multiple traits (e.g., sickle-cell anemia).

• Epistasis: One gene masks or modifies the expression of another (e.g., coat color in Labrador Retrievers).

• Polygenic inheritance: Traits determined by multiple genes (e.g., skin color).

• Environmental effects: Environmental factors can influence phenotype (e.g., diet affecting gene expression).

These complex inheritance patterns illustrate that genetics is not always straightforward and can be influenced by multiple factors, including gene interactions, environmental influences, and epigenetic changes.

Lecture 22: Genes and Chromosomes III - Alterations of Chromosomes

Dr. Ian Smith
BIO93 - UC Berkeley

Key Terminology & Concepts

• X-linked gene: A gene located on the X chromosome. X-linked genes exhibit different inheritance patterns because males have only one X chromosome (XY), while females have two X chromosomes (XX).

• Aneuploidy: A condition in which an organism has an abnormal number of chromosomes. This can result from errors in meiosis, such as non-disjunction, leading to conditions like Down syndrome (trisomy 21).

• Gene linkage: The tendency for genes located close to each other on the same chromosome to be inherited together during meiosis, due to their physical proximity. Linked genes do not assort independently.

• Genomic imprinting: A phenomenon where the expression of certain genes depends on whether the allele is inherited from the mother or the father. This silencing of one allele is epigenetic and involves changes like DNA methylation.

• Parental phenotype: The phenotype (observable traits) of the parents that are typically passed down to offspring, especially when genes are linked.

• Chromosome translocation: A chromosomal abnormality where part of one chromosome is transferred to another chromosome. This can cause disorders such as chronic myelogenous leukemia (CML), where the Philadelphia chromosome results from a translocation between chromosomes 9 and 22.

• Non-parental phenotype: Offspring phenotypes that do not match the parental phenotypes, often resulting from recombination (crossing over) between linked genes.

• Recombination frequency: The percentage of recombinant offspring produced from a genetic cross. It is used to determine the relative distance between two genes on a chromosome.

• Recombinant offspring: Offspring whose genotype differs from both parents due to genetic recombination (crossing over) during meiosis.

• Linkage map: A genetic map that shows the relative locations of genes on a chromosome, based on recombination frequencies.

• X-linked recessive trait: A genetic trait carried on the X chromosome that only appears in males if the allele is present, as males have only one X chromosome. In females, the trait only appears if both X chromosomes carry the allele.

• Barr body: A condensed, inactivated X chromosome in females. Since females have two X chromosomes, one is randomly inactivated in each cell during early development to balance the gene dosage between males (XY) and females (XX).

Learning Outcomes

• Understand how sex-linked genes differ from autosomal genes in inheritance.

• Explain why X-linked recessive diseases are more common in males.

• Describe gene linkage, recombinant chromosomes, and how recombinant offspring are produced.

• Discuss Barr body-dependent inheritance patterns.

• Define and explain genomic imprinting and its implications on inheritance.

• Describe chromosomal alterations, including chromosome translocations, and their impact on genetic disorders.

Historical Background

• 1850s: Mendel's work on hereditary factors.

• 1870s-1890s: Discovery of meiosis and mitosis.

• 1902: Chromosome theory of inheritance.

  • Genes are located on specific positions on chromosomes, which undergo segregation and independent assortment.

  • Missing Link: Solid evidence connecting specific genes to specific chromosomes was lacking until later discoveries.

Key Discoveries by Thomas Hunt Morgan (1933 Nobel Prize)

• White-eye inheritance pattern in Drosophila:

  • Eye color showed up only in males.

  • Morgan concluded that eye color was linked to the sex chromosomes (X chromosome).

  • w+ (wild type red) dominant over w (mutant white).

• Gene Linkage:

  • Genes located on the same chromosome tend to be inherited together, but crossing over during meiosis can break this linkage.

Gene Linkage & Recombination

• Linkage:

  • Genes on the same chromosome are linked and tend to be inherited together.

  • Crossing over during meiosis can occasionally break the linkage, leading to recombinant offspring.

• Recombination Frequency:

  • Recombination frequency (RF) is the percentage of recombinant offspring.

  • RF reflects the distance between linked genes on a chromosome. The further apart the genes, the higher the recombination frequency.

• Linkage Map:

  • A linkage map shows the relative positions of genes on a chromosome based on recombination frequencies.

  • For example, in Drosophila:

    • b (body color) and vg (wing size) have a 17% recombination frequency.

    • cn (cinnabar eye color) and b have a 9% RF.

Sex-Linked Inheritance Patterns

• X-linked Recessive Traits:

  • Traits carried on the X chromosome follow unique inheritance patterns.

  • For example, color blindness is an X-linked recessive trait.

  • Males are more often affected because they have only one X chromosome.

• Barr Body & X-Inactivation:

  • In female mammals, one of the X chromosomes is inactivated during development to balance gene dosage between males (XY) and females (XX).

  • The inactivated X chromosome becomes a Barr body, and its genes are largely silenced.

  • If a female is heterozygous for an X-linked trait, about half of her cells will express one allele, and the other half will express the other allele.

  • Example: Hypohidrotic ectodermal dysplasia causes patches of skin without sweat glands in heterozygous females.

  • Example: Tortoiseshell cats: The orange and black coat patterns are a result of X-inactivation, with different patches of skin expressing different alleles for coat color.

Genomic Imprinting

• Genomic Imprinting:

  • A form of epigenetic inheritance where one allele of a gene is silenced based on the parent of origin.

  • Igf2 gene: This gene is silenced on the maternal chromosome due to DNA methylation and remains active only on the paternal chromosome.

  • Key Point: Genomic imprinting is not due to sex-linkage but involves epigenetic modification during gamete formation.

Chromosomal Alterations

• Alterations of Chromosome Structure:

  • Structural changes in chromosomes can lead to genetic disorders.

• Chromosome Translocation:

  • Translocation occurs when a piece of one chromosome breaks off and attaches to another chromosome.

  • Philadelphia chromosome: A translocation between chromosomes 9 and 22 leads to the formation of the BCR-ABL fusion gene, which is associated with Chronic Myelogenous Leukemia (CML).

  • The BCR-ABL fusion protein is a kinase that disrupts cell cycle regulation.

Polls and Interactive Questions

• Several polls throughout the lecture addressed concepts such as sex-linked inheritance patterns, recombination frequencies, and X-linked recessive traits.

Conclusion

• Understanding the inheritance of genes linked to sex chromosomes, the mechanisms of recombination, and the impacts of chromosomal alterations are essential for explaining various genetic diseases and disorders.

• Concepts like Barr body inactivation, genomic imprinting, and chromosome translocation provide insight into complex patterns of inheritance that do not follow simple Mendelian genetics.

Lecture 23: Regulation of Gene Expression

Key Terminology

1. Transcription factors: Proteins that help regulate gene expression by binding to specific DNA sequences, aiding or hindering the transcription process.

2. TATA box: A DNA sequence found in the promoter region of genes, crucial for initiating transcription in eukaryotic cells.

3. Promoter: A region of DNA that initiates transcription of a particular gene. It contains specific sequences like the TATA box that help recruit transcription factors and RNA polymerase.

4. Enhancers: DNA sequences that increase the transcription of a gene. These can be located far from the gene they regulate and work by binding to transcription factors (activators).

5. RNA Polymerase II: The enzyme responsible for transcribing mRNA from a DNA template in eukaryotic cells.

6. Alternative RNA splicing: A post-transcriptional process where different combinations of exons are joined together to produce multiple protein variants from a single gene.

7. Proteasome: A protein complex responsible for degrading unneeded or damaged proteins by breaking them down into smaller peptides.

Key Concepts

1. Gene Expression and Regulation

• Gene Expression: The process by which information from a gene is used to produce a functional product, typically a protein. The regulation of gene expression allows cells to produce proteins at appropriate times and in response to environmental signals.

• Differential Gene Expression: Differences between cell types are not due to different genes, but because of differential regulation of gene expression. The same set of genes can be expressed in different cells, but at different levels or times.

2. Chromatin Structure and Gene Regulation

• Chromatin: A complex of DNA and proteins (histones) found in the nucleus. It is packaged into a compact structure to fit inside the cell nucleus.

• Histones: Proteins that help package DNA into chromatin. Modifications to histones can regulate gene expression.

  • Histone Acetylation: The addition of acetyl groups to histone tails, which loosens the chromatin structure and promotes transcription.

  • DNA Methylation: The addition of methyl groups to DNA, usually leading to gene silencing. This is a key mechanism in genomic imprinting and X-inactivation.

• Euchromatin vs. Heterochromatin:

  • Euchromatin: Loosely packed chromatin where genes are more actively expressed.

  • Heterochromatin: Tightly packed chromatin, typically found in regions like centromeres and telomeres, where gene expression is often repressed.

3. Transcriptional Regulation

• Transcription Factors: These are proteins that bind to specific DNA sequences to initiate or regulate transcription. There are two main types:

  • Activators: Enhance transcription by binding to enhancer regions.

  • Repressors: Inhibit transcription by binding to silencer regions or preventing activators from binding.

• Control Elements: Sequences in DNA, such as enhancers and silencers, that regulate transcription. They interact with transcription factors to either increase or decrease transcription.

4. Post-Transcriptional Regulation

• RNA Processing: Before mRNA exits the nucleus, it undergoes several modifications, including splicing, capping, and the addition of a poly-A tail. These modifications influence mRNA stability, transport, and translation efficiency.

  • Alternative RNA Splicing: The process by which different combinations of exons are joined to produce different mRNA isoforms, allowing one gene to code for multiple proteins.

  • mRNA Degradation: mRNA molecules have a limited lifespan. In eukaryotes, mRNA degradation is initiated by shortening of the poly-A tail and removal of the 5' cap. Nuclease enzymes break down the mRNA. This process helps control gene expression by regulating how long mRNA remains available for translation.

• Initiation of Translation: Regulatory proteins can bind to the 5' UTR of mRNA to prevent ribosomes from attaching, effectively blocking translation.

5. Post-Translational Regulation

• Protein Processing: After translation, proteins can undergo various modifications such as cleavage, phosphorylation, and glycosylation. These modifications can activate, deactivate, or alter the protein’s function.

• Proteasomal Degradation: Proteasomes are protein complexes that degrade unneeded, damaged, or misfolded proteins by breaking them into smaller peptides. This is a key mechanism for regulating protein levels within the cell.

6. Epigenetics

• Epigenetics: The study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence. This includes DNA methylation and histone modifications.

• Genomic Imprinting: A form of epigenetic regulation where the expression of a gene depends on whether it is inherited from the mother or the father. This involves the silencing of one allele of a gene through DNA methylation or histone modifications.

Overall Summary

• Gene expression is controlled at multiple levels, including transcriptional regulation, post-transcriptionalprocessing, and post-translational modifications.

• Transcription factors, enhancers, and promoters regulate which genes are transcribed and at what rate.

• Chromatin modifications (e.g., histone acetylation and DNA methylation) can alter the structure of chromatin, making it more or less accessible for transcription.

• Alternative RNA splicing and mRNA degradation add additional layers of regulation to ensure proper gene expression.

• Proteins are also regulated after translation through modifications and degradation by the proteasome, further controlling their activity and abundance in the cell.

This multi-layered approach to gene regulation ensures that cells can fine-tune their protein production in response to internal and external signals, which is crucial for cell function, development, and adaptation.

Lecture 24: Genetic Basis of Development

Key Terminology

1. Differentiation: The process by which unspecialized cells become specialized in structure and function to perform specific tasks in an organism.

2. Morphogenesis: The process through which cells develop their shape and organize themselves into tissues, organs, and structures, contributing to the formation of the overall body plan.

3. Cytoplasmic Determinants: Maternal substances (e.g., proteins, RNAs) found in the egg cytoplasm that influence early development by affecting gene expression in the zygote and its subsequent divisions.

4. Induction: A process where certain cells influence the development of adjacent cells through signaling molecules, leading to changes in gene expression and differentiation.

5. Determination: The process that commits a cell to a particular fate. Determination precedes differentiation, meaning the cell's future role is already decided, even before it shows specific structural features.

6. Pattern Formation: The spatial organization of tissues and organs during development. It involves the establishment of body axes and the arrangement of structures in specific locations within the embryo.

7. Positional Information: The molecular signals that provide cells with information about their position relative to other cells, which helps guide the development of body structures.

8. Bicoid: A maternal effect gene in Drosophila (fruit fly) that plays a crucial role in determining the anterior (head) structures of the embryo. Its protein product forms a gradient in the embryo and helps establish the anterior-posterior axis.

9. Cleavage: The series of rapid cell divisions following fertilization, in which the zygote divides without substantial growth, resulting in a multicellular embryo.

10. Blastocyst: A structure formed in early embryonic development (in mammals) that consists of a hollow ball of cells. It is involved in implantation into the uterine wall.

11. Organogenesis: The process during which the germ layers (ectoderm, mesoderm, endoderm) develop into the rudimentary organs of the body.

12. Fertilization: The union of sperm and egg, which results in the formation of a zygote and the activation of the egg.

13. Gastrulation: A developmental process in which cells move to form three distinct germ layers: ectoderm, mesoderm, and endoderm, setting the stage for further development of tissues and organs.

14. Germ Layers:

• Ectoderm: The outermost layer, which gives rise to the skin, nervous system, and sensory organs.

• Endoderm: The innermost layer, which forms the digestive tract, lungs, and other internal organs.

• Mesoderm: The middle layer, which forms muscles, bones, the circulatory system, and other internal structures.

Key Concepts

1. Development Overview

• Embryonic development involves a series of stages, during which a single-celled zygote gives rise to a multicellular organism with various cell types and tissues.

• The fate of cells is determined by cytoplasmic determinants and inductive signals.

• Gene regulation is crucial in orchestrating the differentiation of cells, and morphogenesis shapes the organism's body plan.

2. Cell Differentiation and Morphogenesis

• Differentiation refers to how cells acquire specific structures and functions.

• Morphogenesis refers to the physical shaping of tissues and organs, and this is regulated through changes in cell shape, position, and survival.

3. Cytoplasmic Determinants

• Cytoplasmic determinants are substances (proteins, RNAs) that are asymmetrically distributed in the egg and influence early development.

• As the zygote divides, each cell inherits a unique combination of these determinants, which leads to different patterns of gene expression in the daughter cells.

4. Induction and Cell Communication

• Inductive signals are critical for guiding development. These signals come from neighboring cells and alter gene expression in target cells.

• Through induction, cells can influence each other’s differentiation, ensuring that the correct tissues and organs form in the right places.

5. Determination and Differentiation

• Determination is the commitment of a cell to a specific fate (e.g., becoming a muscle or nerve cell). This occurs before differentiation, where the cell actually begins to take on its specific structure and function.

• For example, Myoblasts are determined to become muscle cells, and the MyoD protein, a master regulatory gene, helps commit these cells to a muscle-specific fate by promoting the expression of muscle-related genes.

6. Pattern Formation

• Pattern formation is the process by which cells organize into specific patterns, creating a structured body plan.

• Positional information is crucial here, guiding cells to differentiate based on their location within the embryo.

• In Drosophila, pattern formation is initiated by the distribution of maternal cytoplasmic determinants in the egg, which helps establish the anterior-posterior axis of the embryo.

7. Bicoid Gene and Morphogen Gradients

• The bicoid gene in Drosophila plays a key role in establishing the anterior end of the body (head).

• Bicoid is a morphogen, meaning it is part of a gradient that helps establish the body’s polarity. The concentration of bicoid protein is higher at the anterior end and lower at the posterior end.

• A loss of functional bicoid results in an embryo lacking a proper head, with two posterior ends instead.

8. Embryonic Development Stages

• Fertilization: The egg and sperm fuse, forming a zygote with a diploid set of chromosomes.

• Cleavage: Rapid cell division without growth, producing a multicellular embryo.

• Gastrulation: The formation of the three germ layers (ectoderm, mesoderm, endoderm).

• Organogenesis: The development of rudimentary organs from the germ layers.

9. Cleavage and Embryonic Patterning

• During cleavage, cells divide without increasing in size, resulting in a blastula, a hollow sphere of cells.

• The vegetal pole (which contains more yolk) and the animal pole (which contains less yolk) influence the pattern of cleavage in many animals.

• The distribution of yolk determines how cleavage occurs and how the embryo will develop.

10. Gastrulation: Formation of Germ Layers

• During gastrulation, cells move and fold to form the three primary germ layers:

  • Ectoderm: Forms the outer structures (skin, nervous system).

  • Mesoderm: Forms internal structures (muscles, bones, circulatory system).

  • Endoderm: Forms the digestive and respiratory systems.

• In frogs, gastrulation begins at the dorsal lip of the blastopore, where cells start moving inward (invagination).

11. Organogenesis: Development of Organs

• After gastrulation, organogenesis begins, where the three germ layers further specialize into specific organs.

• In vertebrates, the neural plate forms from the ectoderm, and the notochord forms from the mesoderm.

• The neural tube, derived from the neural plate, will become the central nervous system (brain and spinal cord).

12. Neural Tube Formation

• The neural plate curves inward, forming the neural tube, which eventually develops into the brain and spinal cord.

• Neural crest cells form along the neural tube and will differentiate into various structures, including parts of the nervous system, teeth, and skull bones.

Summary

Embryonic development is a highly regulated process that transforms a fertilized egg into a multicellular organism. This process is driven by differentiation, morphogenesis, and gene expression regulation, with cytoplasmic determinants and inductive signals guiding early development. Pattern formation establishes the body’s organization, and specific genes, such as bicoid, play key roles in determining the body’s axes and structure. Development proceeds through a series of stages: fertilization, cleavage, gastrulation, and organogenesis, culminating in a fully formed organism.

Lecture 25: The Nervous System 1

Bio 93 - Dr. Kim Green

Key Vocabulary:

• Neuron: A nerve cell that transfers information within the body.

• Brain: The central organ responsible for processing information in the nervous system.

• Ganglia: Simple clusters of neurons involved in information processing.

• Sensory Neurons: Neurons that carry signals from sensory organs to the brain/spinal cord.

• Interneurons: Neurons that process information within the brain and spinal cord.

• Motor Neurons: Neurons that carry signals from the brain/spinal cord to muscles or glands to trigger a response.

• Cell Body: The main part of a neuron that contains the nucleus.

• Dendrites: Branch-like extensions that receive signals from other neurons.

• Axons: Long extensions that transmit electrical signals away from the cell body.

• Synapse (Pre and Post): The junction between two neurons or a neuron and another cell (e.g., muscle or gland).

• Synaptic Terminal: The end of an axon that releases neurotransmitters across the synapse.

• Membrane Potential: The difference in electrical charge across the plasma membrane.

• Resting Potential: The membrane potential of a neuron not transmitting signals (typically -70 mV).

• Ion Channels: Proteins in the membrane that allow ions to pass through (includes voltage-gated channels).

• Hyperpolarization: When the membrane potential becomes more negative than the resting potential.

• Depolarization: When the membrane potential becomes less negative (more positive).

• Action Potential: A rapid, all-or-nothing electrical signal that travels along an axon.

• Threshold: The membrane potential that must be reached for an action potential to occur (around -55 mV).