L1 - Introduction to Molecular Biology – Vocabulary Review

Acknowledgement & Opening Context

• Begins with an Acknowledgement of Country: respect paid to the Wurundjeri People of the Kulin Nation, traditional custodians of the land on which Monash University’s Clayton Campus stands.
• Speaker: Prof. Fasilik Kribali (Biochemistry; unit convener for BMS1062 – Molecular Biology).
• Presence in both lecture themes and laboratory sessions.

Course Structure & Pedagogical Style

• Lectures delivered in several short recordings.
  • Each segment is bracketed by pre- and post-activities designed to consolidate/apply concepts.
  • Strong encouragement to complete these tasks for deep learning.
• Integration of molecular insights from DNA → organism → population levels.

What Is Molecular Biology? – Big-Picture Overview

• Discipline focused on the "many phases of DNA".
• DNA positioned as the “common centre” of all known life forms.
• Visual aid referenced: Tree of Life highlighting universality of DNA.
• Contrasting image: enormous cellular diversity (across species & among the trillions of cell types within a human body) despite identical genomes.
• Diversity arises from differences in each cell’s “machinery of life.”

Cell Machinery Illustration (Slide Description)

• Depicted: plasma membrane separating extracellular space (left) & cytoplasm (right).
• Viruses shown attempting entry—foreshadowing viral exceptions to standard DNA rules.
• Intracellular components highlighted:
  • DNA storage sites.
  • Replication enzymes (green).
  • Transcription apparatus producing RNA intermediates.
  • Translation complexes (ribosomes etc.; blues).

Central Dogma – Simplified Diagram & Deep Significance

• Three boxes, three arrows: DNA → RNA → Protein plus a circular arrow on DNA (self-replication).
• Despite visual simplicity, detailed mechanisms yielded multiple Nobel Prizes.
• Fundamental assertions:
  • DNA = stable genetic repository.
  • Information flow is unidirectional under normal circumstances.
  • Proteins execute metabolic/structural functions.
• Recognised caveats (“dogma is not always correct”):
  • Some viruses encode genetic info in RNA.
  • Reverse information flow possible (e.g., reverse transcription in retroviruses).

Sub-cellular Context of Information Flow in Eukaryotes

• DNA confined to nucleus (and mitochondria, though not pictured in detail).
• Replication and transcription occur in nucleus.
• RNA exported; translation occurs in cytoplasm.
• Proteins distributed throughout cell.

Unit Themes (5) & Their Emphases

1. Theme 1 – Structure & replication of DNA (current focus).
2. (Mentioned as “TIMSS two”) – Gene technologies derived from DNA understanding.
3. Theme 3 – Gene expression (transcriptional processes).
4. Theme 4 – Regulation of gene expression (defines unique cellular identities).
5. Theme 5 – Mutations, DNA repair & recombination in health, disease & immunity.

Lecture-Specific Learning Outcomes

• Understand structure & function of DNA.
• Explain template-based DNA replication.
• Introduce RNA structure/function differences (expanded in Theme 3).

Recommended Multimedia Resources

• Links provided (Moodle):
  • Static illustrations of the double helix.
  • A 3-D interactive DNA animation.
  • Videos covering essential replication, transcription & translation processes.

Historical Milestones in Discovering DNA’s Role

• Mid-1800s: Darwin & Mendel establish heredity rules; molecular substrate unknown.
• Friedrich Miescher (1869): isolates “nuclein” (DNA) from pus & salmon sperm.
  • Notes high phosphorus & nitrogen content and nuclear localisation.

Chemical Composition of Nucleic Acids

• Nitrogenous Bases
  • Pyrimidines (single 6-member ring): cytosine (C), uracil (U), thymine (T).
  • Purines (fused 5- & 6-member rings): adenine (A), guanine (G).
  • Functional group variations allow recognition (knowledge expected in assessments).
• Pentose Sugar
  • Ribose numbered 1'!\rightarrow 5'.
  • DNA = deoxyribose (lacks 2'-OH); RNA retains 2'-OH.
• Nucleoside vs Nucleotide
  • Nucleoside: base + sugar ("S for sugar").
  • Nucleotide: base + sugar + ≥1 phosphate(s) ("T for tri-phosphate" mnemonic, even when mono-/di-phosphate).

DNA vs RNA – Comparative Features

• Polymer length: DNA 10^6 \text{–} 10^7 nucleotides; RNA can be as few as 17 nt.
• Function: DNA stores genes; RNA chiefly supports protein synthesis (mRNA, rRNA, tRNA, etc.).
• Stability: DNA highly stable (long-term storage); RNA intentionally short-lived to allow rapid response to stimuli.
• Localization: DNA in nucleus & mitochondria; RNA found in nucleus, cytoplasm, mitochondria.

Free Nucleotides in Cellular Economy

• ATP: universal energy currency.
• Acetyl-CoA: metabolic intermediate containing nucleotide moiety.
• cAMP: intracellular second messenger in signalling cascades.

Polymerisation & Backbone Architecture

• Phosphodiester bond joins 3'-OH of one nucleotide to 5'-phosphate of next.
• Generates linear, non-branched polymer with polarity: 5' \rightarrow 3'.
• Free 5'-phosphate at one end; free 3'-OH at opposite end.

The Double Helix – Key Structural Insights

• DNA strands entwine into right-handed helix.
• Sugar-phosphate backbone outward; bases stacked inward.
• Base-pairing: A•T and G•C via complementary hydrogen bonding.
• Polarity is antiparallel: one strand 5' \rightarrow 3', partner 3' \rightarrow 5'.

Chargaff’s Rules & Their Mystery

• Empirical observation (Erwin Chargaff):
  [A] = [T]; \; [C] = [G]
  [\text{Purines}] = [\text{Pyrimidines}]
• Ratios conserved across species → provided critical clue for base-pairing model.

X-Ray Crystallography & “Photo 51”

• Rosalind Franklin & PhD student Raymond Gosling produce diffraction pattern.
• Pattern analysis (spot positions/intensities) enables atomic model construction.
• Watson, Crick & Wilkins integrate data → iconic wire-and-ball model (bases inside, phosphates outside).
• Discovery established structural basis for replication & information storage → Nobel Prize (1962) shared among Watson, Crick, Wilkins; Franklin’s pivotal contribution acknowledged posthumously.

3-D Interactive Exploration Activity (Upcoming)

• Students instructed to access the web-based animation.
• Objectives:
  • Trace strand polarity.
  • Visualise major/minor grooves.
  • Examine hydrogen bonding within base pairs.
  • Relate structural features to replication & transcription mechanics.

Ethical, Philosophical & Practical Implications

• Recognition that scientific “dogma” is continually tested; exceptions (viral RNA genomes, reverse transcription) highlight adaptability of life.
• Understanding DNA structure underpins technologies (gene editing, diagnostics, forensics) to be covered in upcoming themes.
• Insight into mutations & repair connects molecular events to diseases (cancer, immunodeficiencies).

Key Terminology for Revision

• Central Dogma
• Nuclein / Nucleic Acid
• Pyrimidine vs Purine
• Deoxyribose vs Ribose
• Nucleoside / Nucleotide
• Phosphodiester Bond
• Antiparallel Strands
• Chargaff’s Ratios
• X-Ray Diffraction / Photo 51

Take-Home Message: DNA’s elegant chemical architecture—double helix, complementary base pairing, directional backbone—explains its dual capacity as a stable genetic archive and a template for faithful replication. Mastery of these fundamentals sets the stage for exploring gene expression, regulation, mutation, and modern biotechnologies in subsequent themes.