RUI: Evolution of Signal Transduction Pathways in Yeast

本项目的目标是了解相关生物体对环境变化的反应中代谢的差异是如何产生的。每一种待研究的真菌物种都经历了略微不同的环境，并且预计每一种物种都将在进化过程中调整其代谢，以最适合该环境。 硫胺素信号转导途径将在酵母种光滑念珠菌和粟酒裂殖酵母中进行研究，并与酿酒酵母中研究充分的途径进行比较。 该项目将回答有关硫胺素（维生素B1）合成如何在这些生物体中调节以及该系统如何演变以影响不同环境中的生长的问题。所有生物体都需要硫胺素，其吸收或合成对生长至关重要。了解硫胺素信号转导途径如何在酵母物种中进化，将使我们更好地了解基因的获得和丢失在多大程度上影响生物体对其环境的反应。该项目将在维拉诺瓦大学（主要是本科院校）进行，并将为维拉诺瓦大学和Immaculata大学的硕士生和本科生提供研究培训和经验。从事该项目的本科生平均将花费两年多的时间进行研究，并将被鼓励对他们的项目负责，并在专业会议上展示他们的数据硫胺素在大多数微生物中从头合成，并且是所有动物的饮食要求。 本项目详细研究了C. glabrata（与模式酵母S. cerevisiae）和S.粟酒这项工作的目标是了解允许这些生物体占据不同环境的进化变化。In S.在酿酒酵母中，硫胺素生物合成基因的转录需要转录因子Thi 2，而这在C.光滑的虽然C. glabrata可以以降低的效率合成硫胺素，它似乎可以有效地从环境中消除硫胺素。这项工作将测试这样的假设：一些酵母物种中Thi 2的获得使得硫胺素合成更有效，而C. glabrata失去了Thi 2，因为它生长在哺乳动物组织中，而哺乳动物组织可能是硫胺素的丰富来源。 该项目将：1）通过rt-qPCR、报告基因融合和交叉互补实验研究硫胺素调控启动子的进化; 2）研究环境生态位的变化，这些变化使得C. glabrata，3）检测C. glabrata PMU基因阵列以产生高度特异性的硫胺素焦磷酸酶，以及4）使用具有给定硫胺素基因网络结构的物种或菌株之间的竞争来检查对适合度的影响。 本项目将阐明1）真菌中硫胺素信号转导/合成途径的进化2）Thi 2转录因子在该途径中的作用3）确定信号转导途径重新布线对环境特化的影响。

The goal of this project is to understand how differences in metabolism have arisen in the response of related organisms to changes in their environment. Each of the fungal species to be studied experiences a slightly different environment and each species is expected to have tailored its metabolism, over evolutionary time, to be best suited for that environment. The thiamine signal transduction pathway will be studied in the yeast species Candida glabrata and Schizosaccharomyces pombe and compared to the well-studied pathway in Saccharomyces cerevisiae. This project will answer questions about how thiamine (vitamin B1) synthesis is regulated in these organisms and how this system has evolved to impact growth in different environments. All organisms require thiamine and its uptake or synthesis is critical for growth. Understanding how the thiamine signal transduction pathways have evolved in yeast species will give a better understanding of the extent to which the gain and loss of genes affects how an organism is able to respond to its environment. This project will be carried out at Villanova University (a primarily undergraduate institution) and will provide research training and experiences for Masters level students and undergraduate students from Villanova and Immaculata University. Undergraduates working on this project will, on average, spend over two years working on their research, and will be encouraged to take responsibility for their projects and to present their data at professional meetings Thiamine is synthesized de novo in most microorganisms and is a dietary requirement in all animals. This project examines in detail the thiamine signal transduction pathways in C. glabrata (a mammalian commensal that is closely related to the model yeast S. cerevisiae) and S. pombe. The goal of this work is to understand the evolutionary changes that have permitted these organisms to occupy different environments. In S. cerevisiae, transcription of the thiamine biosynthetic genes requires the transcription factor Thi2 which is surprisingly lacking in C. glabrata. Although C. glabrata can synthesize thiamine with reduced efficiency it appears to scavenge thiamine efficiently from the environment. This work will test the hypothesis that the gain of Thi2 in some yeast species has allowed for more efficient thiamine synthesis and that C. glabrata lost Thi2 because it grows in mammalian tissues which are likely a rich source of thiamine. The project will: 1) examine the evolution of thiamine-regulated promoters through rt-qPCR, reporter fusions, and cross complementation experiments, 2) examine the changes in environmental niche that have allowed for loss of some thiamine regulatory genes in C. glabrata, 3) examine the neofunctionalization of the C. glabrata PMU gene array to generate a highly specific thiamine pyrophosphatase, and 4) examine the consequences on fitness using competitions between species or strains with given thiamine gene network architectectures. This project will elucidate 1) the evolution of thiamine signal transduction/synthesis pathways in fungi 2) the role of the Thi2 transcription factor in this pathway and 3) determine the impact of signal transduction pathway re-wiring on environmental specialization.