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Monash University > Medicine, Nursing and Health Sciences > Department of Biochemistry and Molecular Biology > Teaching > Science > Bch3021 >

BCH 3021: Cellular Organisation: Organelle structure and function in health and disease

Convenor: Prof Phil Bird
6 points
Monash Handbook

This subject offers the advanced basis for understanding the major themes in Cell Biology. It is a basic Biomedical/Science subject that should be taken for all those embarking on careers in Biotechnology and Biomedical Science involving cell structure and function.

Cellular Organisation: Organelle Structure and Function in Health and Disease deals with the architecture and dynamics of the cell, and examines the impact of disease processes on cellular organelles, protein trafficking and tissue structure. Up-to-date information and examples of cutting-edge cell and molecular techniques are used to present the cell as a flexible, semi-autonomous unit that constantly interacts with its extracellular environment and with other cells. Areas to be covered include:

Structural elements of cells; the integration of cells into tissues; perturbations and reorganization during disease.
Function and formation of organelles; structure and the synthesis of membranes; integration with subcellular scaffolding (cytoskeleton); molecular machines in cellular functions.
The production, processing and targeting of proteins to organelles; effects of mutation on protein biosynthesis and transport; quality control systems.
Communication and transport routes between cells and between organelles; protein sorting and mis-sorting; mechanisms of vesicular trafficking.
Techniques of analysis of cellular components and functions using fluorescent tools such as green fluorescent protein.

Lecturing staff

Colour photo of Phil Bird

Prof Phil Bird

Colour photo of Tim Cole

A/Prof Tim Cole

Colour photo of David Jans

Prof David Jans

Colour photo of Mark Prescott

Dr Mark Prescott

Organisation of the Unit

BCH3021 consists of 2 lectures/week and one 3 hour practical session/week. Two tutorial sessions have been scheduled/week and attendance and active participation in discussion by students at one of these sessions per week is highly recommended.

Topics Covered

Modern Methods in Experimental Cell Biology

Culture, separation, fractionation, and imaging of cells and organelles. Green fluorescent protein.

Structural Elements of Cells

Plasma membrane: Cell membranes: plasma membrane, nuclear membrane, endoplasmic reticulum, mitochondrial membranes. Characteristics of the lipid bilayer. Formation and turnover of the plasma membrane. Membrane proteins, integral and peripheral. Transport across membranes. The glycocalyx.
Cytoskeleton: Nature of the cytoskeleton. Intermediate filaments and their role in maintaining structural integrity. Interaction with plasma membrane in desmosomes and hemidesmosomes. Diseases associated with abnormalities of the cytoskeleton, or desmosomal/hemidesmosomal components.
Intracellular transport: Actin filaments and microtubules. Role in cellular locomotion, cell division and location of organelles within the cell. Motor proteins, focal contacts. Anti-cancer drugs that affect microtubule formation.
Cell membrane interactions: The establishment of functionally separate regions of the plasma membrane: occluding junctions, adhesion belts. Interactions with the basement membrane, cell-cell interactions. Integrins, cadherins as signalling molecules, role in cell polarity, cancer metastasis.

Mitochondria

Bioenergetic aspects of mitochondrial function: Central role of mitochondria in energy conversions. Electron transport to oxygen. ATP synthase. Chemi-osmotic coupling. Oxidative phosphorylation. Inhibitors of oxidative phosphorylation.
Approaches for investigating the structure, function and dynamics of the mitochondrion: Techniques of organelle isolation, gel electrophoresis, electron microscopy, fluorescence microscopy together with the application of fluorescent probes will considered and how they are used to provide important insights into the ultrastructure and dynamic properties of the mitochondrion.
Molecular biology of human mitochondria: Structure of human mitochondrial DNA. Replication and expression of human mitochondrial DNA. Assembly of mitochondrial enzyme complexes from products of mtDNA and nuclear DNA: Limited autonomy of mitochondria. Maternal inheritance of human mitochondrial DNA. Import of proteins into mitochondria
Mitochondrial disease, ageing and oxidative stress: Components of oxidative phosphorylation system vulnerable to mutations in mtDNA. Major clinical features of mitochondrial disease. Examples of mtDNA mutations associated with disease conditions; heteroplasmy and mitochondrial segregation. Nuclear genetic defects in mitochondrial disease. Mitochondria and ageing, as a process of gradual accumulation of molecular damage: reactive oxygen species and cellular defences against oxidative stress.

Nucleus

Structure and function of the nucleus: Structure of the nucleus, the nuclear envelope, and nuclear pore complexes; packaging of DNA into chromosomes; chromosomes organization and replication. Synthesis and modification of RNA and ribosomes; role of the nucleolus.
Transport into and out of the nucleus: Transport of macromolecules into and out of the nucleus; how protein-protein interactions between the different transport components - importins, the monomeric guanine nucleotide binding protein Ran, and nucleoporins - mediate nuclear import/export; how the guanine nucleotide bound state of Ran determines directionality through the nuclear pore.
Regulation of nuclear transport in signal transduction and disease: How nuclear protein transport relates to integral processes such as development, differentiation, transformation and signal transduction.

Endoplasmic Reticulum and Golgi

Structure and biogenesis of the endoplasmic reticulum ( ER) and Golgi complex: Overview of the biogenesis and role of the ER and Golgi in cell biology; the nature and role of the rough and smooth ER; the importance of the cis and the trans Golgi compartments; vesicle traffic; synthesis of proteins destined for intra-organelle and inter-organelle localization.
Biosynthesis and glycosylation of proteins in the ER and Golgi: The biosynthesis and translocation of soluble and membrane-associated proteins into the ER, and beyond; how proteins are folded; how aberrant proteins are recognized and removed; examples of diseases caused by protein misfolding in the ER.
Modification and maturation of secretory proteins: The nature of the post-translational events that occur in the ER; N- and O-linked glycosylation; N-linked and O-linked oligosaccharide synthesis; sulphation; phosphorylation; the role and significance of high mannose structures; recognition sequences for glycosyltransferases; importance of post-translational events in the Golgi.
Protein sorting in the trans-Golgi network: The biosynthesis of glycosaminoglycans; assembly of multi-subunit proteins using collagen as an example; maturation of proteins by proteolysis; implications for infection and disease.

Vesicle Trafficking

Endocytosis: As well as moving proteins to the plasma membrane (secretion), cells must be able to move proteins from the surface to the interior (endocytosis). In many cases, specific proteins are efficiently internalized by receptor-mediated endocytosis. We will discuss the mechanisms of endocytosis with specific reference to the internalization of low density lipoproteins from the blood. Defects in receptor mediated endocytosis of LDL cause familial hypercholesterolemia, which is associated with high risk of heart attack at an early age.
Secretory vesicle structure and trafficking: Proteins moving through the secretory pathway travel in specialized transport vehicles known as vesicles, and precise mechanisms exist to ensure that both proteins and vesicles reach their correct destinations. Here we will discuss the molecular mechanisms that underpin vesicle formation, cargo acquisition, movement and targeting.

Lysosomes and Peroxisomes

Structure and function of lysosomes and peroxisomes: Visualising peroxisomes and lysosomes in cells. A comparison of structure and function; membranes, integral proteins. Enzymes and metabolic pathways. Molecular basis of selected peroxisomal and lysosomal diseases.
Autophagy: The role of the lysosome in autophagy. Different types of autophagy. The molecular biology, mechanism and regulation of macroautophagy.
The pleiotrophic role of autophagy in the cell: Monitoring autophagy in cells and tissues. The role of autophagy in combating metabolic stress, neurodegenerative disorders, cancer and bacterial infection.