NSF Postdoctoral Fellowship in Biology FY 2021: Empirical and theoretical approaches to understanding the evolution of gene regulatory networks

该行动资助2021财年NSF生物学博士后研究奖学金，研究基因组，环境和表型之间相互作用的生命规则的综合研究。该奖学金支持将以创新方式为《生活规则》领域作出贡献的研究员的研究和培训。该项目调查了基因组中基因之间的相互作用，这些相互作用产生了生物体的物理特征。这些相互作用的具体“结构”，即哪些基因相互作用产生一个性状，通常被称为“基因调控网络”（grn）。GRN结构的变化导致了许多生物性状的差异，但这些GRN结构变化是如何发生的还不清楚。了解基因组的变化如何改变grn的结构和性状是一个具有广泛应用价值的重要而具有挑战性的问题。在密歇根大学的Patricia Wittkopp博士和科学哲学家Aaron Novick博士的指导下，该项目将通过使用敏感技术来调查GRN在不同时间尺度和环境中的细微变化来解决这个问题，以阐明讨论和定义GRN的实际方法。该研究员将从事将接触到不同受众的教学和外展活动。拟议的工作将使用遗传模型系统酿酒酵母（啤酒酵母）来研究GRN变异。这将通过使用高灵敏度、高通量流式细胞术技术，评估引入突变对局灶性GRN下游靶点表达水平的影响，特别是TDH3基因及其类似基因TDH1和TDH2。该研究员将通过量化对TDH3及其类似物的不同突变影响来研究物种内发生的GRN结构变化。该项目还将测量环境变化对这些grn结构的影响。最后，这项工作将着眼于相关物种（S. paradoxus）的焦点GRN结构，以检查跨物种GRN的差异。诺维克博士在这个项目上的共同赞助增加了一个跨学科的元素，将被纳入STEM和哲学的教学目标。该研究员还将为学术界的早期职业护理人员建立一个社区空间。该奖学金与获奖者的职业发展目标非常匹配，获奖者将接受新模型系统的培训，掌握尖端的高通量数据收集技术，并接受科学哲学方面的指导。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. The project investigates the interactions between genes in the genome, which give rise to the physical traits of organisms. The specific “structures” of these interactions, that is, which genes interact to produce a trait, are often referred to as “gene regulatory networks” (GRNs). Variation in GRN structure is responsible for many differences in organismal traits, but how these structural changes to GRNs occur is not well understood. Understanding how changes to the genome alter the structure of GRNs and change traits is an important and challenging problem with broad applications. The project will tackle this problem by using sensitive techniques to investigate subtle variations of a GRN over different time scales and environments, under the mentorship of Dr. Patricia Wittkopp at the University of Michigan, and the co-mentorship a philosopher of science, Dr. Aaron Novick, to clarify practical ways to discuss and define GRNs. The Fellow will engage in teaching and outreach activities that will reach diverse audiences. The proposed work will use the genetic model system Saccharomyces cerevisiae (brewer’s yeast) to investigate GRN variation. This will be done by assessing the effects of introduced mutations on the expression levels of downstream targets of the focal GRN, specifically the TDH3 gene and its paralogs TDH1 and TDH2, using a highly sensitive high-throughput flow cytometry technique. The Fellow will examine the changes to GRN structure that have occurred within-species by quantifying the differing mutational effects on TDH3 and its paralogs. The project will also measure the effects of changing environment on the structure of these GRNs. Finally, the work will look at the focal GRN structure in a related species (S. paradoxus) to examine across-species GRN divergence. Dr. Novick’s co-sponsorship on this project adds an interdisciplinary element that will be incorporated into teaching objectives in both STEM and philosophy. The Fellow will also build a community space for early career caregivers in academia. The proposed fellowship represents an exceptional match for the career development goals of the Fellow who will receive training in a new model system, master cutting edge high-throughput data collection techniques, and receive mentoring in philosophy of science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.