NSF Postdoctoral Fellowship in Biology FY 2020: Influence of m6A In Gene Regulation and Protein Occupancy in Bacillus Subtilis

2020 财年 NSF 生物学博士后奖学金：m6A 对枯草芽孢杆菌基因调控和蛋白质占用的影响

• 批准号: 2010735
• 负责人: Nicolas Fernandez
• 金额: $ 13.8万
• 依托单位: Fernandez, Nicolas
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2010735&HistoricalAwards=false
• 关键词: NSF; Postdoctoral; Fellowship; Biology; FY

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2020, Broadening Participation of Groups Under-represented in Biology. The fellowship supports a research and training plan for the Fellow that will increase the participation of groups underrepresented in biology. The Fellow’s research assesses how chemical modifications (methylation) of DNA control how genes are turned on and off. Cells from bacteria to humans have these modifications in their DNA. In bacteria, a major function of methylation is to identify and destroy invading DNA from sources including viruses that infect bacteria. However, the broad occurrence of DNA methylation suggests that methylation is important for other biological processes. The goal of this research is to determine how DNA methylation influences and coordinates the process for gene expression. Due to the prevalence of DNA methylation in bacteria, the knowledge gained will have broad implications. During the course of this research, the Fellow will utilize programs and clubs within the institution to promote research and scholarship for populations under-represented in science.Using the bacterial model organism Bacillus subtilis, the Fellow will utilize in vitro and in vivo assays to determine how DNA methylation, specifically N6-methyladenosine (m6A), influences protein-DNA interactions. Preliminary evidence suggests that DNA binding of the global regulator ScoC is negatively controlled by m6A. The Fellow will analyze the effect of m6A on DNA binding by ScoC to determine how methylation alters DNA binding in vitro. The Fellow will also use targeted and untargeted systems-level approaches to determine how m6A influences protein-DNA interactions in vivo. Results from these experiments will 1) determine the effect of m6A on global DNA binding by ScoC and 2) identify regions of the genome that display methylation-dependent levels of protein binding. By coupling systems analysis with traditional biochemical characterization, the Fellow will take a novel approach to understand the functional consequences of m6A on gene expression and chromosome occupancy which will advance the field of bacterial epigenetics. The Fellow will also develop projects based on this topic that are suitable for summer research opportunities for under-represented populations and science outreach opportunities targeted at middle-school and high-school students. In addition, the Fellow will undertake formal training modules and seminars on college-level teaching and professional development in pursuit of a career in academia.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.

该行动为2020财年美国国家科学基金会生物学博士后研究奖学金提供资金，扩大生物学中代表性不足群体的参与。该奖学金支持研究员的一项研究和培训计划，该计划将增加生物学中代表性不足的群体的参与。该研究员的研究评估了DNA的化学修饰（甲基化）如何控制基因的开启和关闭。从细菌到人类细胞的DNA都有这些修饰。在细菌中，甲基化的一个主要功能是识别和破坏入侵的DNA，包括感染细菌的病毒。然而，DNA甲基化的广泛发生表明甲基化对其他生物过程也很重要。本研究的目的是确定DNA甲基化如何影响和协调基因表达的过程。由于细菌中DNA甲基化的普遍存在，所获得的知识将具有广泛的意义。在这项研究的过程中，研究员将利用机构内的项目和俱乐部来促进在科学领域未被充分代表的人群的研究和奖学金。利用细菌模式生物枯草芽孢杆菌，研究员将利用体外和体内试验来确定DNA甲基化，特别是n6 -甲基腺苷（m6A）如何影响蛋白质-DNA相互作用。初步证据表明，全球调节因子ScoC的DNA结合受到m6A的负性控制。该研究员将分析m6A对ScoC DNA结合的影响，以确定甲基化如何改变体外DNA结合。该研究员还将使用靶向和非靶向系统级方法来确定m6A如何影响体内蛋白质- dna相互作用。这些实验的结果将1)确定m6A对ScoC全球DNA结合的影响，2)鉴定基因组中显示甲基化依赖水平的蛋白质结合区域。通过将系统分析与传统的生化表征相结合，该研究员将采用一种新的方法来了解m6A对基因表达和染色体占用的功能影响，这将推动细菌表观遗传学领域的发展。该研究员还将根据这一主题开发适合于为代表性不足的人群提供夏季研究机会和针对初高中学生的科学推广机会的项目。此外，研究员还将参加关于大学水平教学和专业发展的正式培训模块和研讨会，以谋求在学术界的职业发展。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。