BCH 3042: Cell signal transduction: role in cancer and human disease

• Convenor: Dr A Lawen
• 6 points
• Monash Handbook

Cell signal transduction: role in cancer and human disease deals with the control of cellular growth and differentiation through the molecular signals that regulate key biological activities. this includes many important diseases, including cancer. Areas to be covered include:

• molecular principles of signalling within cells and between cells
• basic mechanisms of cell signalling by which signals from outside the cell result in activation of a variety of cell surface receptors leading to a hierarchical activation of signalling networks resulting in gene transcription
• hormones and endocrine networks, cell surface receptors and receptor families and intracellular signalling
• control of cell function: integration by the action of external signals leading to changes in gene expression
• recent advances in cell growth, differentiation and cell death
• dysregulation of cell signaling in diseases including auto-immune diseases, cancer and human immunodeficiency virus (HIV) infection
• recent advances in biotechnology and applications in the treatment of human cancers

Lecturing Staff

Organisation of the unit

BCH3042 consists of 3 lectures per week and one 3 hour practical session per week.

Topics covered

Basic mechanisms of cell signalling

• Cellular communication between cells and within cells. Basic mechanisms of signal transduction, endocrine, paracrine, autocrine, neuroendocrine. Extracellular signalling molecules, diversity and complexity of interactions with receptors.
• Hormones and hormone families. Peptide and protein hormones, structure and physico-chemical properties, binding proteins and structural domains.
• Cell surface receptors. Major families of cell surface receptors, types of signal transduction involving transmembrane receptors, G-protein-linked receptors, G-proteins.
• Intracellular receptors. Mechanisms of steroid hormone family of intracellular receptors, structural domains, ligand receptor interactions, receptor affinities, steroid/hormone/neurotransmission type signalling events.
• The cell cycle

Disordered intracellular signalling and its role in cancer
development

• Cancer introduction, oncogenes – tyrosine kinase receptors.
• Non receptor tyrosine kinases - src.
• Non receptor tyrosine kinases – BCR-Abl and chronic myeloid leukemia, STI571.
• Phosphosphoinositides – PI 3-kinase.
• Oncogenes and apoptosis Akt signalling.
• Tumour supressor genes - Lipid phosphatases –PTEN.
• Phosphoinositides – Role in vesicular trafficking PtdIns 3-P and myotubularin.
• Tyrosine phosphatases
• EGF receptor signalling
• Glucose transporters and insulin signaling. Regulation of glucose uptake.
• Cytokine signalling.
• From bench to bedside

Apoptosis

• Apoptosis is a regulated form of cellular death, which removes unwanted cells, especially during morphogenesis and the development of the immune system. The name ‘apoptosis' was introduced in 1972 by Kerr et al., the phenomena has been first described in 1842 by Vogt. A deregulation of apoptosis appears to underlie many diseases, including auto-immune diseases, cancer and the destruction of T-cells after human immunodeficiency virus (HIV) infection
• Introduction to cell death.
  Apoptosis versus oncosis and necrosis, phases of apoptosis, analysis of apoptosis, physiological cell death, genetic control of apoptosis, cell homeostasis.
• Apoptosis in development and in the immune system I
  Apoptosis in development, programmed cell death.
  Signalling pathways in B and T-cells. Cell signalling in B and T- cell maturation and differentiation (discrimination of self vs. non-self).
• Apoptosis and the immune system II
  Cell signalling in T-cell mediated immune responses. Apoptosis and lymphocyte development. The bcl-2 gene family.
• Apoptosis and the immune system III
  Apoptosis and HIV. Receptor-mediated apoptosis. Death-inducing signalling complex (DISC) formation and downstream signalling cascades.
• Apoptosis and the immune system IV
  Apoptosis and autoimmune diseases, regulation of autoreactive lymphocytes and immune privileged tissues. The family of TNF receptors, decoy receptors. Ceramide as a second messenger.
• Signalling networks in apoptosis I
  Caspases. Viral defences against apoptosis.
• Signalling networks in apoptosis II
  The intrinsic pathway, the role of mitochondria in apoptosis, cytochrome c release, the apoptosome.
• Signalling networks in apoptosis III
  Apoptosis versus proliferation. c-myc, p53, apoptosis and cancer. Phagocytotic uptake of apoptotic cells. Receptors and recognition signals.