BCHM3072/3972

Human Molecular Cell Biology

Course Information

These course outlines are a guide only. They are provided for the information of prospective students. Although every effort is made to ensure the most up to date information is provided, timetables often change each semester due to the availability of rooms and resources. Content (including lecture/practical topics, assessment and textbooks) is also regularly reviewed to ensure relevance and effective learning.

General Information
Human molecular cell biology is one of the fastest-growing areas in the biomedical sciences. In large part this is a consequence of the array of experimental tools which are now available for studying cellular processes, in both health and disease, at the molecular level.

In this course we will show how these tools have led to recent advances in three related areas: the signal transduction events which arise when cells respond to normal external stimuli, how cells respond to pathological stimuli and how cells control the central events of cell division and programmed cell death under both normal and pathological circumstances.

Particular emphasis will be placed on how an integrated experimental approach has given us insights into the cellular economy.

Mrs Jill Johnston

Room: 410

Telephone: 9351 4248

FAX: 9351 4726

E-mail: j.johnston@usyd.edu.au

Professor Iain Campbell

Room: 710

Telephone: 9351 4676

FAX: 9351 5858

E-mail: icamp@mmb.usyd.edu.au

For BCHM3072
(MBLG (1001 or 1901) and 12 CP of Intermediate BCHM/MBLG units (taken from MBLG2071/MBLG2971or BCHM2071/2971 or BCHM2072/2972)) or (42CP of Intermediate BMedSc units, including BMED2802 and BMED2804)

For BCHM3972
MBLG (1001 or 1901) and Distinction in 12 CP of Intermediate BCHM/MBLG units (taken from MBLG2071/MBLG2971 or BCHM2071/2971 or BCHM2072/2972) or 42CP of Intermediate BMedSc units, with Distinction in BMED2802 and BMED2804.

1st Lecture: Wednesday 9:00am Carslaw Lecture Theatre 157

2nd Lecture: Friday 9:00am Peter Nicol Russell Lecture Theatre

PRACTICAL CLASS TIMES and VENUES
TIMES: Odd weeks, 10:00am - 1:00pm Monday/Tuesday OR Wednesday/Thursday 10:00am - 1:00pm, according to Student Timetable (classes start in Week 3)*
VENUE: All practical classes will be in the Biochemistry 3 lab, Level 4, Biochemistry and Microbiology building, G08

*Note that it is possible to leave the practical class to attend a lecture in another subject, in which case the practical class will finish at 2:00pm.

The recommended textbook is:

Alberts B et al Molecular biology of the cell (5th edition, Garland Science, 2008)


Reference texts

Cooper G M The Cell: A Molecular Approach (4th edition, ASM Press, 2008)

Weinberg R A The Biology of Cancer (Garland 2007)

Infection and Implications for Cell Function
T Newsome: 4 Lectures

Rewiring of the cell cycle and apoptosis
1-2 Once a viral genome gets inside a cell, the first battle it faces is to keep the cell alive. These two lectures will look at the viral proteins that rewire the cell cycle and promote survival: homologues, structural mimics, other mechanisms; DNA viruses and oncogenesis (such as in HPV, cervical cancer); oncolytic viruses; tumour cells with TSGs deleted and oncogenes activated; and at potential therapies with natural and engineered oncolytic viruses.

Actin motility and infection
3-4 These two lectures will look at the role of actin in a cell (intracellular trafficking, phagocytosis, migration, etc) and illustrate the role of polymerisation in the function of actin; the discovery of Arps, ActA and the Arp2/3 complex; the use of structural, biochemical and cell biological approaches in building a function for actin; the regulation of actin polymerisation in a cell; and at the role of N-Wasp in human disease.

Immune Mechanisms and the Molecular Biology of Host Defence
I L Campbell: 8 Lectures

Eukaryotic organisms have evolved crucial mechanisms to defend themselves against infection by potentially harmful invaders, collectively called pathogens. The host response is a well-orchestrated and complex defensive state that follows injury or infection in eukaryotes. This response consists of two interdependent effector processes known as the innate and the adaptive immune responses. Innate and adaptive immune responses work together to eliminate the invading pathogens and protect the organism from any future infection.
This lecture series will discuss the central molecular and cellular components of the innate and adaptive immune systems and how these come together to provide protective immunity.

1. The big picture. Molecular and cellular aspects of innate immunity.
2. Key players. Cytokines of the innate immune response with emphasis on the interferons: their discovery, biology, therapeutic utility and role in disease.
3. Sensing danger. Introducing pattern recognition receptors (PRRs) and their signal transduction pathways, including the Toll-like (TLR) receptor and nucleotide-binding oligomerisation domain (NOD) families as well as other PRRs such as RNA helicases.
4. Taking action. Regulation of interferon gene expression and production via transcriptional control of the type I IFN promoter involving interferon regulatory factors (IRFs), NFkB and other transcriptional factors.
5. Transmitting commands. Signal transduction pathways that mediate cytokine communication: the interferon receptors: the JAK/STAT pathway: negative regulation of JAK/STAT signaling: viral evasion of host defence by interference with IFN-signalling.
6. The weapons arsenal: The molecular basis for the antimicrobial actions of interferons: revelations from global gene expression profiling: the biochemistry of the antiviral state and viral evasion strategies: collateral damage and the pathogenesis of disease.
7. Smart weapons: T-cell development and types, the T-cell antigen receptor, antigen presentation and MHC molecules, molecular basis of effector T-cell function.
8. Smart weapons II: B-cell development, the B-cell antigen receptor, immunoglobulin structure and function.

Cell Proliferation and Apoptosis
R Christopherson: 6 lectures

A cell reproduces by undertaking an orderly sequence of events, known as the cell cycle, in which it replicates its contents and then divides into two. The progress of eukaryotic cells through the cell cycle is controlled by a complex network of regulatory proteins, known as the cell-cycle control system. The final stage in the cellular control system is cell death, usually by a complex sequence of events, programmed cell death, known as apoptosis.
This series of lectures will examine the series of molecular events in the life and death of the cell and will cover an overview of the cell cycle, the cell cycle control system, including the roles of cyclins and cyclin-dependent kinases and their inhibitors, controlled protein degradation (the ubiquitin system), restriction points and checkpoints, the apoptotic pathways (extrinsic and intrinsic). The role of these processes in human disease states will be addressed.

Cellular Signaling Mechanisms: Role in Cell Fate and Tissue Metabolism
A D Conigrave: 5 lectures

In these four lectures, the state of knowledge in the burgeoning field of Cell Signalling Mechanisms will be reviewed, firstly with an overview of the main molecular paradigms that underlie change in cell phenotype and function, and then with an exploration of the interfaces between the upstream receptor-initiated pathways and the downstream functional "cassettes" that control all aspects of cell biology.

1. Molecular organization of receptor-based signalling mechanisms: GPCRs, receptor-tyrosine kinases, Cytokine receptors, Nuclear Receptors
2. Intracellular signalling mechanisms: G-proteins, small molecule second messengers, protein phosphorylation: at the interfaces between signalling pathways and cell fate and function.
3. Cell Signalling mechanisms in the Control of Cell Populations: role of TNF-alpha signalling in rheumatoid arthritis; role of paracrine signalling mechanisms in the control of bone formation and breakdown.
4/5. Cellular Nutrient-Sensing Mechanisms and change in Cell Fate, Metabolism and Function: new insights into mechanisms by which macronutrients change cell, tissue and whole body phenotype and metabolism.

P1 Kinetics of Amino Acid Transport in Erythrocytes (2 weeks) (BCHM3072)
P2 Nitric Oxide Production by Macrophages (2 weeks) (BCHM3972)
P3 Use of Monoclonal Antibodies in ELISA Assays (2 weeks)
P4 Activation of Calcium-pumping ATPase of Cell Membranes by Calmodulin (2 weeks)

Lecture course: 50% (end-of-semester examination)
Practical course: 50% (25% in-semester practical work, 25% end-of-semester examination)