This document provides an overview of a course on cellular organisation. It begins with contact information for the instructor and recommends a textbook. The course structure is then outlined, covering topics such as common cellular features, differences between prokaryotic and eukaryotic cells, important cellular structures, cell signalling, and examples of signal transduction. Key cellular structures that will be discussed include the nucleus, cytoplasm, cytoskeleton, plasma membrane, mitochondria, ribosomes, and endoplasmic reticulum. Model organisms that will be used in the course include yeast, E. coli, and human cells.
This document provides an overview of a course on cellular organisation. It begins with contact information for the instructor and recommends a textbook. The course structure is then outlined, covering topics such as common cellular features, differences between prokaryotic and eukaryotic cells, important cellular structures, cell signalling, and examples of signal transduction. Key cellular structures that will be discussed include the nucleus, cytoplasm, cytoskeleton, plasma membrane, mitochondria, ribosomes, and endoplasmic reticulum. Model organisms that will be used in the course include yeast, E. coli, and human cells.
This document provides an overview of a course on cellular organisation. It begins with contact information for the instructor and recommends a textbook. The course structure is then outlined, covering topics such as common cellular features, differences between prokaryotic and eukaryotic cells, important cellular structures, cell signalling, and examples of signal transduction. Key cellular structures that will be discussed include the nucleus, cytoplasm, cytoskeleton, plasma membrane, mitochondria, ribosomes, and endoplasmic reticulum. Model organisms that will be used in the course include yeast, E. coli, and human cells.
This document provides an overview of a course on cellular organisation. It begins with contact information for the instructor and recommends a textbook. The course structure is then outlined, covering topics such as common cellular features, differences between prokaryotic and eukaryotic cells, important cellular structures, cell signalling, and examples of signal transduction. Key cellular structures that will be discussed include the nucleus, cytoplasm, cytoskeleton, plasma membrane, mitochondria, ribosomes, and endoplasmic reticulum. Model organisms that will be used in the course include yeast, E. coli, and human cells.
[email protected] To provide an overview of cellular organisation, Molecular Cell Biology 6th edition, Eds. Lodish et al., Freeman press This textbook provides a lot of background material to the course and would be a useful resource for the future. In the main library, buy or borrow it from a biochemistry student; parts of the material are also available online at the NCBI website: http://www.ncbi.nlm.nih.gov/books/. In the exam you will not be expected to provide more detail than is provided on these handouts Cellular Organisation: Course structure A recap on your previous studies in biology Cell signalling o Signalling in disease Common features of all cells Prokaryotic vs Eukaryotic cells Overview of important cellular structures o Endocrine, paracrine, autocrine Signal transduction o Signalling networks and systems biology Overview of important cellular structures g g y gy o Receptors, amplification and bifurcation, modulation and integration, transduction o Mode of action of GPCRs Transcription and splicing mRNA export and translation Protein sorting to organelles Examples of signal transduction in cellular organisation o In development: Sonic hedgehog g g Overview of trafficking V i l d d t i t i p g g o In regulated cell death: apoptosis Building on: Macromolecule structure o Vesicles and endocytosis vs exocyctosis Secretory pathway o Role of the rough ER Building on: Macromolecule structure and biosynthesis, Molecular biology of the gene & cell (yr 1) B ildi t d M di i l h i t o Role of the Golgi Building towards: Medicinal chemistry (yr 2), Biological Chemistry (yr 3) Part 1: Cellular Structure Common features of all cells A general (re)introduction to cells, classes of organisms, cellular structure, organelles g ( ) g g Understanding of the fundamental similarities and differences between Pro/Eukaryotes at a morphological and genetic/complexity level a morphological and genetic/complexity level Refresher on cellular structure: structure and general function of key organelles and other cell components Compare and contrast prokaryotic and eukaryotic organisms Identify the main cellular structures and understand their general function Some cells Di iding east cells These single E li i lt l t Dividing yeast cells. These single- celled eukaryotes divide rapidly by budding off new daughter cells. A widely-used model organism, especially E. coli in culture on an agar plate, expressing various colours of fluorescent protein. A prokaryote (bacterium), and the model organism in which our basic knowledge y g , p y valuable for studies of the cell cycle ode o ga s c ou bas c o edge of cellular processes was (and often still is) first discovered 1.1 Common features of all cells Subject to a degree of epigenetic variation Replicate DNA by templated polymerization Replicate DNA by templated polymerization Use proteins (enzymes) as catalysts Use the same molecular building blocks (primary metabolites) One gene can give rise to many proteins (splicing, protein modification) Multiple genes can code for identical or near-identical proteins (multi-copy) Require chemical energy to maintain structure Allows cell to control internal environment, take up and retain nutrients, and dump waste into external environment 1.1 And some fundamental differences Karyon (Gr.) = nut/kernel Pro (Gr.) = before, Eu (Gr.) = true ( ) ( ) Virus (lat.) = toxin; obviously, these are not cells! Can infect both pro- and eukaryotes. Feature Prokaryotes Eukaryotes Viruses Feature Prokaryotes Eukaryotes Viruses Genome size 10 6 base pairs 0.16 x10 6 4 x10 6 10 9 base pairs 0.02 x10 9 670 x10 9 10 3 base pairs 3 x10 3 50 x10 3 Genes 500-5,000 5,000-50,000 4-100 Proteins (proteome) 1000s 100,000s 10s Proteins (proteome) 1000s 100,000s 10s Morphology Single-cell, no nucleus 1+ nuclei (Single- or Multi-cellular) Encapsulated RNA or DNA genome Examples Archea, Bacteria. e.g. causative agents of Fungi (e.g. yeast), Plants, Protozoa (e g malaria Influenza virus, chickenpox, HIV, SARS tuberculosis, typhoid (e.g. malaria parasite), Animals SARS, bacteriophage 1.2 Some model organisms C ll l bi h i t C ll l t b t Cellular biochemistry, molecular biology Cell cycle, signalling, genetics vertebrate and mammalian biology genetics, gene function development gene function, development Rapid life cycle, easily maintained in large numbers Relatively straightforward genetic y g g manipulation (engineering) Genome sequence available Widely available strains standardise Widely-available strains standardise experiments 1.3 Prokaryotes No recognizable intracellular organelles Cytoplasm does not have much structure even Cytoplasm does not have much structure even at very high magnification Have an outer cell wall and inner cell membrane Store DNA in a amorphous region called the Store DNA in a amorphous region called the nucleoid; bacterial genomes are almost always circular, which enables rapid replication Biochemistry simpler than eukaryotes Many important basic mechanisms are very Many important basic mechanisms are very similar (transcription, translation, energy generation, etc.) Rapid replication (minutes) and evolution (e g Lower image: Electron micrograph of Rapid replication (minutes) and evolution (e.g. of resistance) Lower image: Electron micrograph of a longitudinal section through the widely studied bacterium Escherichia coli (E. coli). The cell's DNA is At least 99% of all prokaryotic species remain to be characterised! concentrated in the lightly stained region (termed the nucleoid) 1.4 Eukaryotes Many models have been proposed, based on morphology and on phylogenetic trees (i.e. degree of conservation of genetic sequences between organisms) Early eukaryotes with no photosynthesis or aerobic metabolism enveloped aerobic bacteria or photosynthetic bacteria and formed endosymbiotic associations. These endosymbionts eventually lost most of their genes, many of which were transferred to their host, and became the specialised mitochondria and chloroplasts. 1.5 Recap on (eukaryotic) cellular structure 100 trillion cells in the human body There is no such thing as a typical eukaryotic cell! y Size can range from 10-100 m Very many types; Very many types; there are over 100 types of neuronal cells alone cells alone 1.5 Nucleus The major defining organelle of eukaryotic cells Surrounded by nuclear envelope containing many nuclear pores Contains most of the DNA in the cell The vast majority of DNA is transcriptionally silent (either transcriptionally silent (either switched off or non-transcribed) When a cell is dividing, the DNA and surrounding protein condense into chromosomes that are visible by microscopy. The structure of the nucleus is complex (figure for reference only!) The structure of the nucleus is complex (figure for reference only!) The most prominent structure in the nucleus is the nucleolus, which is the site of transcription of ribosomal RNA (rRNA) and ribosome assembly Specialised cells can be enuculeated (e.g. erythrocytes) or polynucleated (myocytes). Polynucleation is also implicated in the progression of cancer. 1.5 Cytosol, Cytoplasm, Cytoskeleton The "soup" within which cell organelles reside; very viscous due to hi h lt d t i t t high salt and protein content Cytoplasm is the collective term for the cytosol plus the organelles Network of protein fibres that pervades the cytoplasm pervades the cytoplasm Gives the cell its shape and provides the basis for movement K f ll l d Key component of cell cycle and protein transport Contains three types of fibres and Blue: microfilaments; Yellow: microtubules; Green: nuclei molecular motors that pull on them: o Fibres (smallest to largest): microfilaments, intermediate filaments, microtubules microtubules o Motors: Kinesin, Dynein, Myosin 1.5 Plasma membrane A double layer of lipids (lipid bilayer); very complex structure, high protein content (receptors, pores, enzymes) Responsible for the controlled entry and exit of ions (Na, K, Ca, Cl), nutrients, signalling molecules Electron micrograph and cartoons of the plasma membrane of a human red blood cell in cross section. 1.5 Mitochondria elongate cylinders to spheroids, 3-5 m long by 0.5-1.0 m diameter. g y 20 to 1,000/cell, depending on activity required; up to 20% of cell volume Double membrane: inner membrane Double membrane: inner membrane contains numerous folds (cristae) Regenerates ATP by oxidative phosphorylation. Major centre of cellular respiration I k i ith it d bi ti i i t i Mit h d i l DNA (16 kb b t 37 In keeping with its endosymbiotic origin, contains Mitochondrial DNA (16 kb, about 37 genes) and prokaryote-like ribosomes (mitoribosomes) Matrix contains most of the enzymes of the tricarboxylic acid cycle and the urea cycle. Inner membrane contains the components of the electron transport chain. 1.5 Ribosomes Small particles (18-22nm), in cytosol and studding the surface of the rough ER The site for all protein synthesis in the cell p y Often in clusters called polyribosomes or polysomes held together by a strand of mRNA Ribosome Nascent Ribosome mRNA Nascent peptide chain 1.5 Endoplasmic reticulum (ER) Found in all non-enucleated eukaryotic cells, and has structural continuity with the nucleus; 50% of the total membrane of a cell Composed of flattened sheets, sacs, & p tubes of membranes in a convoluted 3D membrane network enclosing internal spaces Internal volume is called the Lumen (up to 10% of cell's volume) Smooth ER: lipid and bile biosynthesis (e.g. prostaglandins), and detoxification f t i of toxins Rough ER: studded with ribosomes, makes, transports, and packages proteins into membrane vesicles 1.5 Golgi Size: 1-3 m by 4-7 m; formed of membranes stacks (cisternae), up to 100 per cell, with three parts: cis- medial- and trans-Golgi Constantly in flux (cisternal maturation): y ( ) vesicles from ER join to form the cis- Golgi and mature through to the trans- Golgi where they reform into new vesicles. A key part of the endo and exocytotic A key part of the endo- and exocytotic pathways. Endocytosis: packaging of t ll l l l f i t l extracellular molecules for internal use. Exocytosis (secretion): packaging and delivery of newly synthesised proteins f The Golgi. a) under a light microscope; b) tomographic reconstruction (blue: cisternea; purple: vesicles) and carbohydrates for extra-cellular secretion 1.5 Lysosomes A cytoplasmic single-membrane vesicle, containing hydrolytic enzymes that operate at pH 5.0. The lysosomal membrane has an ATP-driven proton pump that lowers the internal pH. Protein and organelle recycling/degradation: recycle intact and non-functional cell Protein and organelle recycling/degradation: recycle intact and non functional cell components (autophagy), and break down food/foreign bodies (phagocytosis). However, the major regulatory protein-degradation pathway occurs in the cytoplasm via proteosomes proteosomes. 1.6 Summary Prokaryotes have a much simpler cellular organisation How do these organelles come together to orchestrate cellular organisation? Eukaryotes (in a generic sense) are the focus of this course o Synthesis, sorting and trafficking of proteins o Controlling cellular processes via cell signalling Nucleus Cytoskeleton Pl b o Programming cell division and cell death Plasma membrane Mitochondria Ribosomes Endoplasmic Reticulum Golgi Lysosomes Lysosomes We will discuss others, such as vesicles and centrioles later in the course.