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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要所有细菌基因产物中约有30％是微生物“暗物质”，没有表征功能。开发用于描述共生和致病细菌基因功能的方法推进基本细菌科学和微生物发病机理的领域，推动新方法战斗抗生素耐药性的兴起。该建议的短期培训目标是为候选人提供心理和培训计算生物学和数据科学。长期目标是建立强大的计算和用于非特征细菌基因功能分析的遗传工具。这些将适用于已建立的可访问的实验系统，以使生物膜中的未表征化的机械发现形成和多数菌相互作用。对于职业发展，候选人将进行由杰出的心理，联合和咨询委员会与杰出的全面培训计划。 AIM 1将使用化学遗传学来识别共生中的假设基因功能致病细菌肠球菌OG1RF。在AIM 2中，候选人将发展化学遗传学确定预先形成的生物膜在用生物活性化合物（例如抗生素。在AIM 3中，这些功能基因组学方法将扩展到研究之间 OG1RF和口服病原体链球菌突变，因为候选人确定链球菌杀死 OG1RF和通过未知机制对粪肠球菌的抗性分离菌。一起，这个研究将在医学相关细菌中产生基因功能的基因组规模描述并定义新因素有助于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机构环境。这很高协作环境具有潜水的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。 U明尼苏达州还提供出色的职业开发机会，U明尼苏达州基因组学中心是最先进的设施候选人已经建立了一项富有成效的合作。拟议的培训和研究将是一个平台，候选人将通过该平台发起独立的研究职业将功能基因组学与体外模型系统结合起来研究假设潜水细菌中的基因功能。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
作者：
通讯作者：

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
影响因子：
0
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.