Structural Analysis of a Conserved Alphaproteobacterial Stress Response Pathway

描述（由申请人提供）：细菌细胞利用双组分信号蛋白和可选sigma （σ）因子来调节转录以响应环境应激。众所周知，这些环境应激调节蛋白在许多细菌病原体中起着必不可少的毒力因子的作用。细菌应激反应在细菌生长、生物膜形成、发病和共生等方面起着重要作用。笔者提出的新月形Caulobacter crescentus一般胁迫信号通路的结构研究，将极大地增进我们对α变形菌中胁迫适应的分子和结构基础的认识，该通路集双组分信号和替代调控为一体。克罗森实验室有一个成功的记录，利用技术从广泛的学科追求问题集中在分子微生物生理学。他们广泛的跨学科方法有望提供对细菌细胞如何感知和适应环境变化的更完整的理解。我在克罗森实验室的博士后培训，重点是PhyR， σT和NepR蛋白的分子生物物理学和结构生物学，这将有助于我成功过渡到一个独立的教师职位，在那里我的研究将集中在微生物信号的分子方面。

DESCRIPTION (provided by applicant): Bacterial cells utilize both two-component signaling proteins and alternative sigma (σ) factors to modulate transcription in response to environmental stress. These environmental stress regulatory proteins are known to function as essential virulence factors in numerous bacterial pathogens. Bacterial stress responses play a fundamental role in bacterial growth, biofilm formation, pathogenesis and symbiosis. My proposed structural studies on the Caulobacter crescentus general stress signaling pathway, which integrates feature of two-component signaling and alternative s regulation, will significantly enhance our understanding of the molecular and structural basis of stress adaptation in the alphaproteobacteria. The Crosson lab has a successful track record utilizing techniques from a wide range of disciplines to pursue questions focused on molecular microbial physiology. Their broad interdisciplinary approaches promise to provide a more complete understanding of how bacterial cells can perceive and adapt to changes within their environment. My postdoctoral training in the Crosson Lab, focused on molecular biophysics and structural biology of the PhyR, σT and NepR proteins, will facilitate my successful transition into an independent faculty position, where my research will center on molecular aspects of microbial signaling.