NSF Postdoctoral Fellowship in Biology FY 2021: Maximizing power to uncover the molecular mechanisms between genotype and phenotype

这一行动为NSF 2021财年生物学博士后研究奖学金提供了资金，综合研究调查了支配基因组、环境和表型之间相互作用的生命规则。该奖学金支持研究员的研究和培训，这些研究员将以创新的方式为生活规则领域做出贡献。蛋白质是勤劳的分子，对所有生命过程都是必不可少的。DNA为构建这些蛋白质提供了指令：DNA中的基因被转化为RNA模板分子，再转化为蛋白质分子。然而，从一段DNA(一个基因)产生的RNA分子的数量并不一定能预测由该RNA产生的蛋白质分子的数量。这种不完美的关系本身可能是在DNA中遗传编码的，这可能提供有关其他生命过程的遗传编码如何进化的信息。为了更好地了解DNA中RNA和蛋白质水平是如何遗传编码的，以及这种编码可能是如何产生的，这位研究员将使用秀丽线虫(微小蠕虫)比较同一有机体内两种不同版本基因产生的RNA和蛋白质。这项研究将改善利用线虫研究各种生物过程的大型科学界可用的遗传资源。这项工作还将通过对一名高中生的参与和长期指导来扩大对科学的参与，该高中生来自历史上在科学界代表性较低的群体，并通过交流该研究员的研究和残疾人士的职业生涯。该研究员将首先通过分析来自五个野生型菌株杂交的等位基因特异性RNA测序数据来表征线虫RNA表达变异的遗传控制，从而研究从基因型到表型的分子步骤和进化基因组模式。该项目将通过评估种群基因组背景来询问潜在的RNA表达变化的进化模式。为了验证这样一种假设，即近距离遗传变异在RNA转化为蛋白质的过程中缓冲了表达，该研究员将通过设计高度敏感的量化表位标签来研究个体动物中一组候选基因的等位基因特异性蛋白质水平。该研究员将接受灵活的科学职业生涯培训，通过专业知识扩展、编码和实验设计研讨会的开发和实施，以及对高中和潜在的本科生的长期指导；这种指导将通过吸引历史上代表性不足的群体的成员来扩大研究的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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. Proteins are industrious molecules that are essential to all life processes. DNA provides instructions for building these proteins: genes in the DNA are converted into RNA template molecules that are translated into protein molecules. However, the number of RNA molecules that are produced from a stretch of DNA (a gene) does not necessarily predict the number of protein molecules produced from that RNA. This imperfect relationship may itself be genetically encoded in DNA, which could provide information about how the genetic encoding of other life processes has evolved. To better understand how RNA and protein levels are genetically encoded in DNA and how this encoding may have come to be, the Fellow will compare RNA and protein produced from two different versions of genes within the same organism using Caenorhabditis elegans nematodes (tiny worms). This study will improve the genetic resources available to the large scientific community that uses C. elegans to study diverse biological processes. This work will also broaden participation in science via engagement and long-term mentorship of a high schooler from a group historically underrepresented in science and via communication of the Fellow’s research and disability-accessible career journey.The Fellow will investigate the molecular steps and evolutionary genomic patterns along the genotype-to-phenotype path by first characterizing the genetic control of RNA expression variation in C. elegans by analyzing allele-specific RNA sequencing data from crosses among five wild-type strains. The project will interrogate the evolutionary patterns underlying RNA expression variation by evaluating population genomic contexts. To test the hypothesis that genetic variants in close proximity buffer expression in the translation of RNA into protein, the Fellow will investigate allele-specific protein levels of a set of candidate genes within individual animals by engineering epitope tags for highly sensitive quantification. The Fellow will be trained for a flexible career in science via expertise expansion, coding and experimental design workshop development and implementation, and long-term mentoring of a high school and potentially undergraduate student; this mentorship will broaden the impact of the research by engaging members of historically underrepresented groups.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.