MOLECULAR MECHANISMS INVOLVED IN SACCHAROMYCES CEREVISISAE CELLULAR RESPONSE TO HEAVY METAL AND OXIDATIVE STRESS
Eukaryotic cells, from yeast to mammals, respond and adapt to environmental stressors by evolutionary conserved multicomponent endogenous systems that utilise a network of signal transduction pathways to regulate the adaptive and protective phenotype. Changes in the chemical or physical conditions of the cell that impose a negative effect on growth demand rapid cellular responses, which are essential for survival. Molecular mechanisms induced upon exposure of cells to such adverse conditions are commonly designated as stress responses.
Heavy metals (fe, zn, cu, mn, ni, co) play an important role in cell metabolism, especially as coenzymes and cofactors in various cellular processes. Usually, the environmental concentrations of such elements are low and cells must develop active transport processes to accumulate them. On the other hand, when the concentration of these metals gets higher than the physiological levels, they become toxic, mainly by non-specific binding to proteins or by interference to other metals' metabolism. To absorb and maintain a balance of potentially toxic metal ions, the cells utilize poorly understood mechanisms involving a large number of membrane transporters and metal binding proteins with overlapping substrate specificities and complex regulation.
The baker’s yeast Saccharomyces cerevisiae is an excellent model system to study the molecular mechanisms involved in responses to various stressors, as many conserved proteins and mechanisms have their counterparts in yeast. In this project, we propose to use Saccharomyces cerevisiae cells to investigate:
1) the calcium-mediated response to heavy metal stress.
2) induction of unfolded protein response (UPR) by heavy metal stress.
3) correlation between oxidative stress and heavy metal stress.
Abstract.doc