Lecture 7: Cell Signalling

Introduction to Cell Signalling

• Process by which an extracellular stimulus (neurotransmitter or hormone) changes cell function.
• Fight or flight response: mediated by adrenaline.
• Nerve-to-nerve signalling: mediated by glutamate.

Ion Channels and Receptors

• Ion Channels: Proteins in the membrane allowing ion flow to initiate signalling.
  • Ion selectivity is a key feature.
• Receptors: Bind extracellular ligands triggering events leading to cellular changes.

Ion Channels

• Calcium (Ca²⁺): Ubiquitous signalling ion essential for processes like fertilization and nerve transmission.
• Ion Movement: Requires channel and carrier proteins due to charge prevention of free diffusion.
• Channel Proteins: Water-filled pores allowing ion diffusion through membranes.
  • Most are gated, opening and closing based on cellular conditions.
• Carrier Proteins: Undergo conformational changes to transport ions across membranes.

Ion Gradients

• Found within organelles.
  • ER: higher internal concentration.
  • Lysosome: higher protons (low pH) than cytosol.
  • Mitochondria: subtle proton gradients.
• Active vs. Passive Transport: Movement down a concentration gradient is passive; against it requires ATP (active).

Ion Pumps

• Na⁺/K⁺ ATPase Pump: Ejects 3 Na⁺ ions out, imports 2 K⁺ ions in against gradients.
• P-type ATPases: Involve phosphorylation for ion transport.
• Calcium Pumps (PMCA & SERCA): Transport calcium against concentration gradients.

Ion Channel Types

• Voltage-Gated (VG): Opened by voltage changes.
• Ligand-Gated: Opened by molecule binding.
• Mechanically Gated: Opened by mechanical force.

Selectivity and Structure of K Channels

• Selectivity via 4 oxygen atoms binding K⁺, stabilizing it more than Na⁺.
• Positively charged residues detect voltage changes, controlling channel gates.

Lecture 8: Membrane Potential

Basics of Membrane Potential

• Difference in voltage inside vs. outside cell, typically -70mV at rest.
• Action Potentials: Transient change allowing communication via synapses.
• Equation: Takes into account ion permeability and concentration gradients.

Action Potential Mechanism

• VG Na⁺ Channels: Open during depolarization, raising membrane potential.
• VG K⁺ Channels: Open slower, contributing to repolarization.

Synaptic Transmission

• Voltage-Gated Channels: Trigger neurotransmitter release.
• Ligand-Gated Channels: Allow ions like Na⁺ to flow, causing depolarization.

Neurological Disorders

• Epilepsy: Imbalance of excitation and inhibition.
• Glutamate Receptors: Tetramers, excitatory due to Na⁺ and Ca²⁺ influx.
• GABA Receptors: Pentamers, inhibitory due to Cl⁻ influx.

Lecture 9: Receptor Proteins and Signalling

Receptor Locations

• Typically on cell surface; some intracellular.
• Ligands must cross membranes to bind.

Molecular Switches

• Phosphorylation: Turns proteins on/off using phosphate from ATP.
• GTP-binding Proteins: Use GTP for activation.

G-Protein-Coupled Receptors (GPCRs)

• Activated by hormones, neurotransmitters, odorants.
• Heterotrimeric Structure: Alpha, beta, gamma subunits.
• Signalling Cascades: Activated by different G-proteins, mobilizing messengers.

Enzyme-Linked Receptors

• RTKs: Activated by growth hormones; quicker activation compared to GPCRs.
• Signal Transduction: Involves dimerization, autophosphorylation, and recruitment of proteins like Grb-2 and Sos.

Lecture 10: Developmental Biology 1

Model Organisms

• Conservation of developmental processes allows studying organisms like zebrafish to understand human embryology.
• Embryo Micromanipulation: Techniques to alter embryos for study.
• Genetic Knockouts: Used to study gene function by disabling specific genes.

Early Development

• Cleavage Stages: Rapid cell division without growth.
• Transition to Asynchronous Division: Mid-blastula transition involving zygotic transcription.

Gastrulation and Germ Layers

• Ingression: Individual cell movement.
• Invagination: Coordinated inward movement of cell sheets.
• Involution: Cells migrate under outer layer surface.

Evolutionary Developmental Biology

• Regulative Development: Potential restricted by signals, not just determinants.
• Inductive Signals: Influence cell fate based on competence.
• Morphogens: Signal molecules influencing gradients and cell differentiation.

Developmental Biology 2 & 3

Commitment Mechanisms

• Determination vs. Specification: Commitment to cell fate.
• Localized Determinants: Influence cell fate, studied in organisms like nematodes.
• Embryonic Inductions: Signals from surrounding cells affecting fate.

Gene Expression and Differentiation

• Gene Batteries: Sets of genes required for specific cell types.
• Transcription Factors: Bind to enhancers to regulate gene expression.

Transdifferentiation

• Plasticity in Cell Fate: Ability to switch cell types under experimental or natural conditions.
• Reprogramming: Inducing pluripotency or switching cell fates using transcription factors.

Virology Lecture 1

Characteristics of Viruses

• Inert without a host, primarily RNA genomes.
• Zoonosis: Viruses jumping between species.

Virus Structure

• Capsid Types: Helical, icosahedral, complex.
• Phages: Viruses that infect bacteria.

Virus Classification

• Phylogenetic Trees: Show diversity and unknown virus families.
• Metagenomics: Used to discover new virus sequences.