Cell Signalling and Cell Death
The average adult human body contains one million, billion cells. Each second of each day, approximately one million of these cells will be in the process of apoptosis, or programmed cell death.
Apoptosis is an inbuilt self-destruct mechanism essential for normal development, maintenance and functioning of body tissues and the immune system. However inappropriate activation of the mechanisms for apoptosis can cause or exacerbate diseases including autoimmune disease, degenerative diseases, and cancer.
This division will investigate the molecular mechanisms by which cells undergo apoptosis, and the regulatory and signalling pathways that determine whether the cell death mechanism activates.
- Cell signalling pathways activated by growth factors and cytokines that regulate self-renewal, cell survival, and cell death
- Molecular mechanisms of cell death
- Activation and regulation of Bcl-2 family proteins, Bax and Bak.
Apoptosis is a complex and highly controlled process that has a pivotal role in normal development and function of almost all of the body’s cells. There are a variety of pathways that lead to apoptosis, which are controlled by a range of signals coming from both outside and from within the cell.
Defects in the cellular pathways that control apoptosis have been implicated in a range of diseases. Failure of cells to self-destruct can allow them to accumulate, and prevent elimination of cells that are infected or carry mutations, eventually leading to cancer. Failure of immune cells to die when they should can predispose to autoimmunity. On the other had, inappropriate activation of the cell death mechanism can exacerbate neurodegenerative and cardiovascular diseases.
We study the mechanisms that regulate and implement the cell death program in the hope of developing further therapies that can prevent or abrogate these defects. We use genetic and biochemical approaches to isolate, identify and characterise components of the cell death mechanism, including:
- The Bcl-2 family of proteins, some of which promote cell death and others that inhibit cell death.
- Tumour Necrosis Factor (TNF) superfamily receptors and ligands, that either directly lead to apoptosis or activate transcription factors such as NF-kB and AP1.
- Inhibitor of Apoptosis proteins (IAPs) that prevent cell death by regulating receptor signalling, or by directly inhibiting caspases.
Professor David Vaux (Division Head)
Scientific Coordinator: Catherine McLean - contact Molecular Genetics of Cancer Division