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

该行动资助了2021财年的NSF生物学博士后研究奖学金，即调查基因组，环境和表型之间相互作用的生命规则的综合研究。该研究金支持研究员的研究和培训，以创新的方式为生活规则领域做出贡献。该项目研究基因组中基因之间的相互作用，从而产生生物体的物理特征。这些相互作用的特定“结构”，即哪些基因相互作用以产生性状，通常被称为“基因调控网络”（GRNs）。GRN结构的变异导致了生物体性状的许多差异，但GRN的这些结构变化是如何发生的尚不清楚。了解基因组的变化如何改变GRNs的结构和改变性状是一个重要而具有挑战性的问题，具有广泛的应用。该项目将通过使用敏感技术来解决这个问题，以调查GRN在不同时间尺度和环境中的微妙变化，在密歇根大学Patricia Wittkopp博士的指导下，以及科学哲学家Aaron Novick博士的共同指导下，以澄清讨论和定义GRN的实际方法。该研究员将从事面向不同受众的教学和外联活动。拟议的工作将使用遗传模型系统酿酒酵母（啤酒酵母），以调查GRN的变化。这将通过使用高灵敏度高通量流式细胞术技术评估引入的突变对局灶性GRN的下游靶点（特别是TDH 3基因及其旁系同源物TDH 1和TDH 2）的表达水平的影响来完成。研究员将通过量化TDH 3及其旁系同源物的不同突变效应来研究物种内发生的GRN结构变化。该项目还将衡量不断变化的环境对这些全球网络结构的影响。最后，这项工作将着眼于一个相关物种（S。paradoxus），以检查跨物种的GRN分歧。诺维克博士对这个项目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。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。拟议的奖学金代表了一个特殊的匹配的研究员谁将接受培训，在一个新的模型系统，掌握尖端的高通量数据收集技术，并接受指导的科学哲学的职业发展目标。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.