Cooperation and conflict in microbial systems: sucrose metabolism in yeast

简介（由申请人提供）：该候选人目前为麻省理工学院物理系Alexander van Oudenaarden教授实验室的Pappalardo博士后研究员。该候选人因在单分子生物物理学领域的研究而被授予加州大学伯克利分校物理学博士学位。在博士后期间，候选人正在向系统生物学领域过渡。候选人将从以前的研究中应用定量技术来研究微生物系统的进化博弈动力学。美国国立卫生研究院独立之路奖将在此过渡期间为候选人提供必要的支持。该奖项将允许候选人继续获得体内实验生物学技术的新技能，特别是细菌和酵母细胞培养，流式细胞术以及分子遗传学和分析的使用。该候选人已经制定并参与了一项研究计划，研究葡萄球菌糖代谢的合作进化。在博士后阶段，候选人将：(1)发展理论和实验方法来理解蔗糖代谢的本质；(2)探索蔗糖代谢中的合作和竞争相互作用；(3)研究空间结构对合作相互作用进化的影响。这些目标将通过基因工程改造酿酒葡萄球菌的“合作者”和“骗子”菌株，并在液体培养中直接竞争培养这些菌株来实现。这些竞争实验的结果将通过荧光显微镜和流式细胞术的结合来监测。在奖项的独立阶段，候选人将把研究扩展到大肠杆菌产生清除铁的铁载体的合作和竞争相互作用。候选人最终希望从事研究和教学方面的学术事业。相关性：合作的进化是进化生物学中的一个经典问题，对癌症和传染病的研究具有重要意义。多细胞生命是细胞合作的一个主要例子；当一个细胞停止这种合作并开始不受控制地分裂时，癌症就产生了。同样，传染病的毒性可能取决于感染微生物与宿主之间合作或竞争相互作用的性质。

DESCRIPTION (provided by applicant): The candidate is currently a Pappalardo Postdoctoral Fellow in the laboratory of Professor Alexander van Oudenaarden in the Department of Physics at the Massachusetts Institute of Technology. The candidate was awarded a PhD in Physics from the University of California, Berkeley for research in the field of single- molecule biophysics. During the Postdoctoral Fellowship, the candidate is transitioning to the field of systems biology. The candidate will apply the quantitative techniques from previous research to the study of evolutionary game dynamics in microbial systems. The NIH Pathway to Independence Award would provide necessary support to the candidate during this transition period. The award would allow the candidate to continue to acquire new skills in the techniques of in vivo experimental biology specifically the use of bacterial and yeast cell culture, flow cytometry, and molecular genetics and analysis. The candidate has developed and engaged in a research proposal to study the evolution of cooperation in S. cerevisaie sucrose metabolism. During the Postdoctoral phase of the award, the candidate will 1) Develop theoretical and experimental approaches to understand the nature of sucrose metabolism 2) Explore cooperative and competitive interactions in sucrose metabolism 3) Study the effect of spatial structure on the evolution of cooperative interactions. These aims will be accomplished by genetically engineering "cooperator" and "cheater" strains of S. cerevisiae and growing these strains in direct competition in liquid culture. The results of these competition experiments will be monitored through a combination of fluorescence microscopy and flow cytometry. During the independent phase of the award, the candidate will extend the research to the cooperative and competitive interactions that govern the production of iron-scavenging siderophores by the bacteria E. coli. The candidate ultimately desires to pursue an academic career in research and teaching. Relevance: The evolution of cooperation is a classic problem in evolutionary biology with important implications for the study of cancer and infectious diseases. Multi-cellular life is a prime example of cellular cooperation; cancer results when one cell ceases this cooperation and begins to divide uncontrollably. Similarly, the virulence of infectious diseases can depend upon the nature of cooperative or competitive interactions between infecting microbes and the host.