Functional genomics of hypothetical genes in Gram-positive bacteria

革兰氏阳性菌假设基因的功能基因组学

• 批准号: 10463540
• 负责人: Julia Laura Elizabeth Willett
• 金额: $ 11.23万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-06 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463540
• 关键词: Advisory Committees; Aftercare; Animal Model; Animals; Antibiotic Resistance; Antibiotics; Architecture; Arginine; Automobile Driving; Bacillus subtilis; Bacteremia; Bacteria; Bacterial Genes; Bacterial Physiology; Bacterial Proteins; Bacteriology; Basic Science; Biological Models; Biomedical Research; CRISPR interference; Collaborations; Communities; Complement; Computational Biology; Computing Methodologies; DNA; Data Science; Dental; Dental caries; Dose; Endocarditis; Enterococcus; Enterococcus faecalis; Escherichia coli; Exposure to; Gene Cluster; Genes; Genetic; Genomic approach; Genomics; Goals; Gram-Positive Bacteria; Growth; Guilt; In Vitro; Infection; Knowledge; Libraries; Liquid substance; Measures; Medical; Mentors; Metabolism; Methodology; Methods; Microbe; Microbial Biofilms; Microbiology; Minnesota; Modeling; Molecular; Nature; Outcome; Pathogenesis; Pathway interactions; Pharmaceutical Preparations; Phase; Phenotype; Pheromone; Polysaccharides; Production; Public Health; Research; Resistance; Resources; Shapes; Streptococcus; Streptococcus mutans; System; Techniques; Technology; Testing; Training; Universities; Vancomycin Resistance; Virulence; Work; antagonist; bacterial community; bacterial genetics; career; career development; chemical genetics; collaborative environment; combat; commensal bacteria; dark matter; dental agent; drug resistant pathogen; extracellular; fitness; functional genomics; gene discovery; gene function; gene product; genome-wide; in vitro Model; in vivo; interest; large datasets; microbial; microbial community; microbiome; mutant; novel; novel strategies; oral pathogen; pathogen; pathogenic bacteria; phenotypic data; professional atmosphere; professor; response; tenure track; tool; transposon sequencing; veterinary science

Project Summary/Abstract Approximately 30% of all bacterial gene products are microbial “dark matter” and have no characterized function. Developing methods for describing gene function in commensal and pathogenic bacteria will advance the fields of fundamental bacteriology and microbial pathogenesis, driving new approaches to combat the rise of antibiotic resistance. The short-term training goal of this proposal is to provide the candidate with mentoring and training in computational biology and data science. The long-term objectives are to establish robust computational and genetic tools for functional analysis of uncharacterized bacterial genes. These will be applied to established, tractable experimental systems to make mechanistic discoveries about uncharacterized loci involved in biofilm formation and polymicrobial interactions. For career development, the candidate will undertake a comprehensive training plan with an outstanding mentor, co-mentor, and advisory committee. Aim 1 will use chemical genetics to identify hypothetical gene function in the commensal and pathogenic bacterium Enterococcus faecalis OG1RF. In Aim 2, the candidate will develop chemical genetics methodology to determine how pre-formed biofilms respond after treatment with bioactive compounds such as antibiotics. In Aim 3, these functional genomics approaches will be expanded to study interactions between OG1RF and the oral pathogen Streptococcus mutans, as the candidate determined that S. mutans kills OG1RF and a vancomycin-resistant isolate of E. faecalis through an unknown mechanism. Together, this research will generate genome-scale descriptions of gene function in medically relevant bacteria and define mechanisms by which novel factors contribute to biofilm formation and interactions between microbes. The University of Minnesota provides an ideal institutional environment for this work. This highly collaborative environment has diverse microbiology and computational biology research groups from biomedical, dental, veterinary, and basic science backgrounds. U Minnesota also offers exceptional career development opportunities, and the U Minnesota Genomics Center is a state-of-the-art facility with which the candidate has already established a productive collaboration. Together, the proposed training and research will be a platform from which the candidate will launch an independent research career combining functional genomics with in vitro model systems to study hypothetical gene function in diverse bacteria.

项目概要/摘要 大约 30% 的细菌基因产物是微生物“暗物质”，并且没有特征 开发描述共生菌和病原菌基因功能的方法。 推进基础细菌学和微生物发病机制领域的发展，推动新的防治方法 抗生素耐药性的上升。 本提案的短期培训目标是为候选人提供以下方面的指导和培训： 计算生物学和数据科学的长期目标是建立强大的计算和数据科学。 用于对未表征的细菌基因进行功能分析的遗传工具将应用于已建立的、 易于处理的实验系统，可对生物膜中涉及的未表征基因座进行机械发现 为了职业发展，候选人将进行一项研究。 全面的培训计划，由杰出的导师、共同导师和顾问委员会组成。 目标 1 将使用化学遗传学来鉴定共生和共生体中假设的基因功能。 致病菌粪肠球菌 OG1RF 在目标 2 中，候选人将开发化学遗传学。 确定预先形成的生物膜在用生物活性化合物处理后如何反应的方法，例如 在目标 3 中，这些功能基因组学方法将扩展到研究抗生素之间的相互作用。 OG1RF 和口腔病原体变形链球菌，候选者确定变形链球菌可杀死 OG1RF 和一种耐万古霉素的粪肠球菌通过未知的机制结合在一起。 研究将对医学相关细菌的基因功能进行基因组规模的描述，并定义 新因素促进生物膜形成和微生物之间相互作用的机制。 明尼苏达大学为这项工作提供了理想的制度环境。 协作环境拥有来自不同微生物学和计算生物学研究小组 生物医学、牙科、兽医和基础科学背景也提供出色的职业。 发展机会，明尼苏达大学基因组中心是一个最先进的设施， 候选人已经建立了富有成效的合作。 拟议的培训和研究将共同​​成为一个平台，候选人将在该平台上启动 独立研究职业功能结合基因组学与体外模型系统来研究假设 不同细菌中的基因功能。

项目成果

Problems with Peer Review Shine a Light on Gaps in Scientific Training.

• DOI: 10.1128/mbio.03183-22
• 发表时间: 2023-06-27
• 期刊: mBio
• 影响因子: 6.4

Optimized replication of arrayed bacterial mutant libraries increase access to biological resources.

阵列细菌突变体文库的优化复制增加了生物资源的获取。

• DOI: 10.1101/2023.04.25.537918
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Willett,JuliaLE;Barnes,AaronMT;Brunson,DebraN;Lecomte,Alexandre;Robertson,EthanB;Dunny,GaryM
• 通讯作者: Dunny,GaryM

Optimized Replication of Arrayed Bacterial Mutant Libraries Increases Access to Biological Resources.

• DOI: 10.1128/spectrum.01693-23
• 发表时间: 2023-08-17
• 期刊: MICROBIOLOGY SPECTRUM
• 影响因子: 3.7
• 作者: Willett, Julia L. E.;Barnes, Aaron M. T.;Brunson, Debra N. N.;Lecomte, Alexandre;Robertson, Ethan B. B.;Dunny, Gary M. M.
• 通讯作者: Dunny, Gary M. M.