Spoligotype patterns evolve through the deletion of spacer sequences that cannot be recovered and have provided Dr Mark Tanaka with a rich source of data with which to understand the transmission of disease.
Oxidative Stress Sensing and Cell Cycle Control
Cell division is tightly regulated in eukaryotic cells for the preservation of genetic material in the progeny. When subjected to several forms of oxidative stress, cells respond by delaying cell division allowing repair of cellular damage. Sensing and signalling of oxidative stress are therefore integral to the control of the cell cycle and its deregulation has implications in cancer and neurodegenerative diseases. Yeast provides an excellent model organism for addressing the molecular basis of cell cycle control since many genes involved are conserved from yeast to human and some of these genes are easy to manipulate by molecular biology techniques. Using the mutant library strain collection, high-throughput screening and microarray analysis, we are studying the effect on cell division of chemicals that produce reactive oxygen species. Using this approach, we identified 45 mutants that no longer delay in the cell cycle when subjected to oxidative stress. Among these mutants is the cell-cycle transcription factor Swi6p which encodes a cysteine residue in its protein structure that can function as a redox-sensor.
The project aims to address the fundamental question of how cells sense oxidative stress and respond by delaying in cell division. In particularly, Swi6p and its sensing cysteine participate as well as to coordinate with other players (kinases, phosphatases) in the signalling of oxidative stress and cell-cyle regulation.
Selected References (available on request)
- Fong, C.S., Temple, M.D., Alic, N., Chiu, J., Durchdewald, M., Thorpe, G.W., Higgins, V.J. and Dawes, I.W. (2007) Oxidant-induced cell-cycle delay in Saccharomyces cerevisiae: the involvement of SWI6 transcription factor. FEMS Yeast Res., 8, 386-99
- Alic, N., Higgins, V.J., Breitenbach, M. and Dawes I.W. (2003). In Saccharomyces cerevisiae, a lipid hydroperoxide activates the mitogen-activated protein kinase Mpk1p, independently of the cell-cycle regulating Oca1p. J. Biol. Chem. 278, 41849-41855.
BABS personnel that are responsible for this project