Clegg 1 (1)
Cell Structure, Function, and Principles of Development
Bacterial Cells
Reference Fig. 27.2 to visualize bacterial cell structure.
Introduction to Cell and Developmental Biology
Reference animal cell in Fig. 6.8.
Background of Speaker: Dennis O. Clegg
BS, Biochemistry
PhD, Biochemistry
Postdoc, Neuroscience
Professor since 1988
Focus areas: Stem Cell Biology, Neuroscience, Bacterial Behavior, Plant Biochemistry.
Regenerative Patch Technologies, LLC (RPT)
A California biotechnology company developing cell-based implant technology for retinal diseases.
Founders: Drs. Mark Humayun, David R. Hinton, and Dennis O. Clegg.
Technology for CPCB-RPE1 implant is licensed from USC, Caltech, and UC Santa Barbara.
Course Schedule and Format
Lectures outlined on the course platform (Canvas).
Lectures 2 and 3 will be asynchronous next Monday and Tuesday; they will be available online and not in-person.
Office Hours
In-person after lectures at Campbell Hall, 9:00 AM.
Online via Zoom on Fridays, 9:30-10:30 AM.
Specific dates: November 21, December 5.
Zoom meeting details provided.
Quizzes
Quiz Schedule:
Quiz 6: Opens November 21, closes November 25.
Quiz 7: Opens December 5, closes December 9.
Final Exam
Scheduled for December 12 at 8 AM.
The Cell Biology segment is based on lecture material; additional reading is for understanding.
Learning Objectives for Cell and Developmental Biology
Understand how macromolecules constitute cells and how cells form tissues.
Explore the structure and function of various cellular components.
Investigate methodologies for studying cells experimentally.
Examine the relationship between cellular defects and diseases.
Learn fundamental principles of development in biological systems.
Explore potential cellular therapies.
Case Study: Traumatic Spinal Cord Injury
Individual Case: Jake Javier from Danville, CA (2016).
Incident: Sustained severe trauma to the C5 and C6 vertebrae after his head hit the bottom of a pool.
Result: Immobility and near-drowning experience.
Spinal cord neurons: Functionality comprises sending motor commands and sensory information between the body and brain.
Central Nervous System neurons: Not capable of regeneration.
Scientific Study Reference
Functional recovery mediated by a polymer scaffold seeded with neural stem cells.
Authors and affiliations from various prestigious institutions and publication details.
Clinical Cases
Kris Boesen: Young man paralyzed post-car accident, regained function in hands/arms after receiving 10 million embryonic stem cell-derived neural cells at USC.
Microscopy Techniques
Types of microscopy:
Brightfield (unstained & stained specimens)
Phase-contrast microscopy
Differential interference contrast (Nomarski)
Fluorescence microscopy
Confocal microscopy
Super-resolution microscopy
Scanning Electron Microscopy (SEM)
Transmission Electron Microscopy (TEM)
Comparing Microscopy Techniques
Light Microscopy:
Live or dead specimen; resolution ~0.2 µm; images in color.
Electron Microscopy:
Only for dead specimens (dried); highest resolution (2 nm); images black and white.
Diffusion and Cell Size
Molecules in solution exhibit random motion, leading to diffusion from high-to-low concentration areas until even.
Factors affecting diffusion rates:
Size of molecules (larger molecules diffuse slower).
Temperature and concentration gradient size.
Importance of Cell Size
Cells are small to maximize surface-to-volume ratio to enable efficient nutrient/waste exchange.
Prokaryotic cells average 1–2 µm in diameter;
Eukaryotic cells average 10–20 µm in diameter.
Surface-to-volume ratio calculated to demonstrate why smaller cells maintain efficiency.
Cellular Organisms
Two types:
Unicellular Organisms: Single-celled, e.g., bacteria.
Multicellular Organisms: Composed of many cells capable of more functions, e.g., humans.
Three Domains of Life
Prokaryotes: Bacteria and Archaea.
Eukaryotes: Includes fungi, protists, plants, and animals.
Features Shared by Prokaryotes and Eukaryotes
DNA is the genetic material.
Cells are membrane-bound and contain ribosomes.
Both perform similar metabolic processes (e.g., TCA cycle, glycolysis).
Structure of Prokaryotic Cells
General features:
Plasma membrane present.
Some possess a rigid cell wall made of peptidoglycan (unlike plant cells which have cellulose walls).
DNA is free within the cytoplasm (nucleoid, no nucleus).
May have flagella for locomotion, pili for adherence and DNA exchange.
The Flagellar Motor
Flagella responsible for swimming; powered by H+ gradient, details of structural components.
Prokaryotic Pili
Functionality includes:
Adhering bacteria to surfaces and each other.
Facilitating transfer of plasmids between cells during conjugation.
Antibiotic Mechanism: Penicillin
Discovery by Alexander Fleming in 1928:
Targeted bacterial cells by inhibiting their cell wall synthesis.
Distinction: Human cells lack cell walls, hence unaffected.
Historical Case of Penicillin
Patient case in 1942 marked the first successful treatment with penicillin, demonstrating dramatic recovery.
Characteristics of Eukaryotic Cells
Typically larger, containing organelles, a nucleus, and a complex cytoskeleton.
Animal and Plant Cell Structures
Description of organelles within:
Animal Cells: Centrosomes, mitochondria, Golgi apparatus, etc.
Plant Cells: Include chloroplasts, central vacuole, cell wall, etc.
Detailed Organelles and Their Functions
Mitochondria: Energy production and apoptosis, size, growth by binary fission.
Chloroplasts: Photosynthesis facilitation, thylakoid membranes for pigment binding.
Endomembrane System
Structure includes:
Rough and Smooth ER, Golgi Apparatus, Lysosomes, Vesicles.
Functionality related to protein synthesis, modification, and transport.
Pathways of Protein Synthesis and Transport
Overview from ER to Golgi for secretory proteins.
Roles in processing and delivery of insulin.
Lysosomes and Disease Association
Role in recycling cellular materials and implications in lysosomal storage diseases (e.g., Tay-Sachs Disease).
Importance of Protein Localization Signals
Description of nuclear localization signals (NLS).
Functions in import of proteins through nuclear pores using importin.
Conclusion and Quiz Preparations
Recap of critical concepts in cell biology, emphasizing structure/function relationships and mechanisms relevant to health and disease. Potential quiz questions suggested for review.
End of Lecture Material
Cell Structure, Function, and Principles of Development
This section introduces the fundamental building blocks of life, from the molecular components of cells to their organization into complex tissues and organisms, and explores their developmental principles.
Bacterial Cells
Reference Fig. 27.2 to visualize the general structural organization of a bacterial cell, which is typically a prokaryotic cell lacking a membrane-bound nucleus and other organelles.
Introduction to Cell and Developmental Biology
Reference Fig. 6.8 to understand the typical structure of an animal cell, which represents a eukaryotic cell type with complex internal organization.
Background of Speaker: Dennis O. Clegg
BS, Biochemistry
PhD, Biochemistry
Postdoc, Neuroscience
Professor since 1988
Focus areas: Stem Cell Biology (investigating the potential of undifferentiated cells), Neuroscience (studying the nervous system), Bacterial Behavior (exploring microbial activity and interactions), Plant Biochemistry (analyzing chemical processes in plants).
Regenerative Patch Technologies, LLC (RPT)
A California biotechnology company developing advanced cell-based implant technology specifically for treating various retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
Founders: Drs. Mark Humayun, David R. Hinton, and Dennis O. Clegg.
Technology for CPCB-RPE1 implant (Cell-based patch containing Retinal Pigment Epithelium) is licensed from USC, Caltech, and UC Santa Barbara, highlighting a collaborative effort in research and development.
Course Schedule and Format
Lectures are comprehensively outlined on the course platform (Canvas) to guide student learning.
Lectures 2 and 3 will be asynchronous next Monday and Tuesday; they will be available online for flexible access and will not be conducted in-person.
Office Hours
In-person after lectures at Campbell Hall, 9:00 AM, providing a direct opportunity for interaction.
Online via Zoom on Fridays, 9:30-10:30 AM, offering convenience for virtual attendance.
Specific dates: November 21, December 5.
Zoom meeting details will be provided through the course platform.
Quizzes
Quiz Schedule:
Quiz 6: Opens November 21, closes November 25, allowing several days for completion.
Quiz 7: Opens December 5, closes December 9, providing another window for assessment.
Final Exam
Scheduled for December 12 at 8 AM.
The Cell Biology segment is based exclusively on lecture material; additional reading is recommended for deeper understanding and context but is not directly tested.
Learning Objectives for Cell and Developmental Biology
This course is designed to equip students with a comprehensive understanding of cellular and developmental processes:
Understand how macromolecules (like proteins, nucleic acids, lipids, and carbohydrates) constitute cells and how these cells organize into specialized tissues and organs.
Explore in detail the intricate structure and diverse function of various cellular components, including organelles and their molecular machinery.
Investigate methodologies for studying cells experimentally, including various microscopy and biochemical techniques.
Examine the critical relationship between cellular defects and the etiology of numerous diseases, highlighting cellular pathology.
Learn fundamental principles of development in biological systems, from fertilization to adult multicellularity.
Explore potential cellular therapies, including stem cell applications and regenerative medicine approaches.
Case Study: Traumatic Spinal Cord Injury
Individual Case: Jake Javier from Danville, CA (2016).
Incident: Sustained severe trauma to the C5 and C6 vertebrae (cervical spine) after his head hit the bottom of a pool, leading to a catastrophic injury.
Result: Immobility and a near-drowning experience due to paralysis, indicating significant neurological damage affecting motor and sensory functions.
Spinal cord neurons: Functionality comprises sending vital motor commands from the brain to the body and relaying sensory information back to the brain. Damage to these neurons disrupts communication pathways.
Central Nervous System neurons: Neurons within the brain and spinal cord are generally not capable of significant regeneration after injury, making spinal cord injuries particularly challenging.
Scientific Study Reference
Functional recovery mediated by a polymer scaffold seeded with neural stem cells: A pioneering study demonstrating a potential therapeutic approach for spinal cord injury.
Authors and affiliations from various prestigious institutions and publication details underscore the rigor and collaborative nature of such research.
Clinical Cases
Kris Boesen: A young man paralyzed after a car accident, who remarkably regained function in his hands and arms after receiving 10 million embryonic stem cell-derived neural cells at USC due to a clinical trial. This case highlights the potential of stem cell-based interventions for neurological repair.
Microscopy Techniques
A variety of techniques are employed to visualize cells and their components:
Brightfield (unstained & stained specimens): Basic light microscopy; stained specimens enhance contrast.
Phase-contrast microscopy: Enhances contrast in unstained, living specimens by exploiting differences in refractive index.
Differential interference contrast (Nomarski): Provides a 3D-like image of unstained, living specimens by detecting gradients of refractive index.
Fluorescence microscopy: Uses fluorochromes to label specific molecules or structures, imaging their distribution.
Confocal microscopy: Uses a pinhole to eliminate out-of-focus light, providing sharper, higher-resolution images of thick specimens.
Super-resolution microscopy: Techniques that overcome the diffraction limit of light microscopy to achieve resolutions below nm.
Scanning Electron Microscopy (SEM): Provides detailed 3D surface images by scanning a focused electron beam over the specimen's surface.
Transmission Electron Microscopy (TEM): Allows visualization of internal cell structures by transmitting electrons through ultra-thin sections of a specimen.
Comparing Microscopy Techniques
Light Microscopy:
Can be used for live or dead specimens; resolution is limited to approximately µm (or nm) due to the wavelength of visible light; images can be in color.
Electron Microscopy:
Only for dead, dehydrated, and often chemically fixed specimens; offers the highest resolution, down to nm, because electrons have a much shorter wavelength than light; images are typically black and white.
Diffusion and Cell Size
Molecules in solution exhibit random thermal motion (Brownian motion), leading to diffusion from areas of high concentration to low concentration until a uniform distribution (equilibrium) is achieved. The rate of diffusion is described by Fick's Law.
Factors affecting diffusion rates:
Size of molecules: Larger molecules encounter more resistance and diffuse slower.
Temperature: Higher temperatures increase molecular kinetic energy, speeding up diffusion.
Concentration gradient size: A steeper gradient (larger difference in concentration) leads to faster diffusion.
Surface area and distance: Larger surface area and shorter diffusion distance increase apparent rates.
Importance of Cell Size
Cells maintain small dimensions to maximize their surface-to-volume ratio (), which is crucial for efficient nutrient uptake and waste removal. As a cell grows, its volume increases faster than its surface area, reducing the ratio and hindering efficient exchange.
Prokaryotic cells average µm in diameter, exemplifying optimal for simplicity.
Eukaryotic cells average µm in diameter, often compensating for larger size with internal compartmentalization and transport systems.
Surface-to-volume ratio calculations demonstrate mathematically why smaller cells (or cells with highly folded membranes, like microvilli) are more efficient in material exchange.
Cellular Organisms
Two types, based on cellularity:
Unicellular Organisms: Composed of a single cell, capable of carrying out all life functions independently, e.g., bacteria, yeast, amoebas.
Multicellular Organisms: Composed of many specialized cells working cooperatively, allowing for complex functions, e.g., humans, plants, and fungi.
Three Domains of Life
Based on ribosomal RNA analysis, all life is categorized into three overarching domains:
Prokaryotes: Include Bacteria (diverse group, e.g., E. coli) and Archaea (often found in extreme environments, e.g., halophiles, thermophiles). They are typically single-celled organisms without a membrane-bound nucleus.
Eukaryotes: Includes fungi, protists, plants, and animals. Characterized by cells with a true nucleus and other membrane-bound organelles.
Features Shared by Prokaryotes and Eukaryotes
Despite their differences, both prokaryotic and eukaryotic cells share fundamental characteristics vital for life:
DNA is the genetic material, encoding all cellular information.
Cells are membrane-bound by a plasma membrane, regulating passage of substances.
Both contain ribosomes, the machinery for protein synthesis.
Both perform similar basic metabolic processes (e.g., glycolysis for glucose breakdown, TCA cycle for energy generation in aerobes).
Both utilize ATP as their primary energy currency.
Structure of Prokaryotic Cells
General features of prokaryotes (Bacteria and Archaea):
Plasma membrane present: A lipid bilayer that encloses the cytoplasm.
Some possess a rigid cell wall made of peptidoglycan (in bacteria, offering structural support and protection) or pseudopeptidoglycan/other polymers (in archaea), distinct from plant cells which have cellulose walls.
DNA is free within the cytoplasm, typically organized into a nucleoid region (no true nucleus).
Cytoplasm contains ribosomes (smaller than eukaryotic ribosomes) and various enzymes.
May have flagella for locomotion (e.g., swimming), pili (fimbriae) for adherence and conjugation, and a glycocalyx (capsule or slime layer) for protection and adhesion.
The Flagellar Motor
Bacterial flagella are complex protein appendages responsible for swimming motility. They are powered by the proton motive force (H+ gradient) across the plasma membrane, acting like a rotary motor. The primary components include the basal body (embedded in the cell envelope), the hook (linking the basal body to the filament), and the filament (the helical propeller).
Prokaryotic Pili
Functionality includes:
Adhering bacteria to specific surfaces (e.g., host tissues) and to each other, forming biofilms.
Facilitating the transfer of plasmids (small, circular DNA molecules) between cells during conjugation (bacterial 'sexual' reproduction via sex pili), leading to genetic exchange and antibiotic resistance dissemination.
Antibiotic Mechanism: Penicillin
Discovery by Alexander Fleming in 1928, revolutionized medicine.
Targeted bacterial cells by specifically inhibiting the synthesis of their peptidoglycan cell wall, preventing cross-linking of peptidoglycan strands.
Distinction: Human cells lack cell walls, making penicillin selectively toxic to bacteria and generally harmless to human cells.
Historical Case of Penicillin
A critical patient case in 1942 marked the first successful treatment with penicillin for a systemic bacterial infection, demonstrating dramatic recovery and ushering in the antibiotic era.
Characteristics of Eukaryotic Cells
Typically much larger (10-100 µm) and more structurally complex than prokaryotic cells, containing a true membrane-bound nucleus, numerous specialized membrane-bound organelles, and a complex cytoskeleton for shape and internal transport.
Animal and Plant Cell Structures
Description of organelles within, each with specific roles:
Animal Cells: Characterized by the presence of centrosomes (involved in cell division), mitochondria (powerhouses of the cell), Golgi apparatus (modifies and packages proteins), lysosomes (for waste breakdown), and a lack of a cell wall or chloroplasts.
Plant Cells: Include all animal cell organelles plus chloroplasts (for photosynthesis), a large central vacuole (for turgor and storage), and a rigid cell wall (composed primarily of cellulose) outside the plasma membrane.
Detailed Organelles and Their Functions
Mitochondria: Often called the "powerhouses" of the cell, responsible for generating the majority of cellular ATP through cellular respiration (oxidative phosphorylation). They also play a critical role in apoptosis (programmed cell death). Mitochondria are typically rod-shaped, grow by binary fission, and contain their own circular DNA, supporting the endosymbiotic theory of their origin.
Chloroplasts: Found in plant cells and algae, these are the sites of photosynthesis, converting light energy into chemical energy (ATP and NADPH) through light-dependent reactions within thylakoid membranes, which contain pigments like chlorophyll. This energy is then used in the Calvin cycle to fix carbon dioxide into sugars. Chloroplasts also contain their own DNA and replicate via fission, another example of endosymbiosis.
Endomembrane System
A functionally integrated network of intracellular membranes that regulates protein traffic and performs metabolic functions. It includes:
Rough Endoplasmic Reticulum (RER): Studded with ribosomes, involved in synthesizing and modifying secreted and membrane proteins.
Smooth Endoplasmic Reticulum (SER): Lacks ribosomes, involved in lipid synthesis, detoxification, and calcium ion storage.
Golgi Apparatus: Further modifies, sorts, and packages proteins and lipids into vesicles for secretion or delivery to other organelles.
Lysosomes: Contain hydrolytic enzymes for digesting cellular waste and foreign materials.
Vesicles: Small membrane-bound sacs involved in transport within the cell.
Pathways of Protein Synthesis and Transport
Overview from ER to Golgi for secretory proteins: Proteins destined for secretion, insertion into membranes, or delivery to certain organelles (like lysosomes) are synthesized on ribosomes bound to the RER. They enter the ER lumen, undergo folding and glycosylation, and are then transported via transport vesicles to the Golgi apparatus for further processing, sorting, and packaging. The Golgi acts as a central sorting and distribution center.
Roles in processing and delivery of insulin: As a secreted protein hormone, insulin undergoes synthesis on RER ribosomes, enters the ER lumen for folding and disulfide bond formation, travels to the Golgi for further processing (e.g., cleavage of proinsulin to insulin), and is then packaged into secretory vesicles for release from the cell in response to high blood glucose.
Lysosomes and Disease Association
Lysosomes contain a diverse array of digestive enzymes (acid hydrolases) that break down macromolecules, old organelles, and foreign substances. Their function is crucial for cellular recycling and waste management. Dysfunctions in specific lysosomal enzymes lead to lysosomal storage diseases (e.g., Tay-Sachs Disease, where a defective enzyme results in the accumulation of gangliosides in nerve cells, leading to severe neurodegeneration).
Importance of Protein Localization Signals
Description of nuclear localization signals (NLS): Specific amino acid sequences found on proteins that target them for import into the nucleus. These signals are recognized by cytosolic receptor proteins called importins.
Functions in import of proteins through nuclear pores (large protein complexes in the nuclear envelope) using importin. This process is energy-dependent, typically requiring GTP hydrolysis by the small G-protein Ran, ensuring regulated movement of proteins into the nucleus.
Other localization signals exist for targeting proteins to mitochondria (Mitochondrial Targeting Sequence, MTS), chloroplasts, peroxisomes, and the ER (ER signal peptide).
Conclusion and Quiz Preparations
Recap of critical concepts in cell biology, emphasizing the intricate structure/function relationships of cellular components and the underlying molecular mechanisms relevant to health and disease. Students are encouraged to review potential quiz questions suggested for review and to focus on integrating knowledge across different topics to prepare for assessments.