Mechanisms of Regulation of the Unfolded Protein Response

点击翻译按钮获取中文摘要

The capacity to adapt to environmental stresses is critical for the viability of all life forms. The molecular players and pathways by which microbes respond to stress are often evolutionarily conserved in higher organisms. It is therefore common that the initial discoveries for how living cells adapt to stressful situations are first made while studying simple organisms like bacteria and yeast. A major goal of my research program is to identify the mechanisms by which cells adapt to the stress of having their proteins become unfolded, commonly known as the unfolded protein response (UPR). This evolutionarily conserved stress adaptation is found in all higher organisms and is used to overcome a number of environmental challenges. The inability to activate an effective UPR has also been implicated in disease states. To study common strategies of how cells mount an effective UPR, we are using the model organism Schizosaccharomyces pombe (fission yeast). We use fission yeast because of the richness of scientific tools available for this organism; there are well-established and available methods for both its genetic and biochemical manipulation. Furthermore, for several metabolic processes, fission yeast has been characterized as the most representative microbe in terms of evolutionary conservation with higher organisms, including humans. Preliminary data from both our and other groups indicate that fission yeast mount an effective UPR in a significantly different way than has been elucidated in other simple organisms, and as such the study of this stress response in this living system may provide us with unique insight into how other cells, including human cells, adapt to stress. Thus, my research program is dedicated to addressing the lack of knowledge about the unfolded protein response in S.pombe and to examine the nature of its evolutionary conservation and divergence. The elucidation of mechanisms of stress adaptation in S. pombe will be useful in extrapolating related pathways in higher organisms, will provide insight into the characterization of microbial growth conditions, and may assist in the design of new anti-microbials.