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The Effect of Multicellularity on Bacterial Interactions and Diversity

多细胞性对细菌相互作用和多样性的影响

基本信息

批准号：
9509481
负责人：
Nicholas Anthony Lyons
金额：
$ 8.86万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9509481
关键词：
Actinobacteria class Affect Altruism Amino Acid Substitution Amino Acids Antibiotic Resistance Antibiotics Award Bacillus (bacterium)Bacillus subtilis Bacteria Bacterial Physiology Behavior Bioinformatics Biological Biological Assay Biology Catalogs Cells Complement Complex Cooperative Behavior DNA Sequencing Facility Data Data Set Development Discrimination Distant Drug resistance Evolution Exhibits Foundations Future Gene Expression Genes Genetic Transcription Genomics Goals Habitats Health Human Infection Knowledge Learning Life Style Light Mediating Mentors Mentorship Microbial Biofilms Microbiology Modeling Mutation Organism Output Pharmaceutical Preparations Phase Phenotype Population Postdoctoral Fellow Prevention Production Recording of previous events Research Research Personnel Resources Role Route Scientist Social Environment Solid Source Streptomyces Stress Structure System Technical Expertise Techniques Testing Training Variant Work antimicrobial bioinformatics resource career career development clinically relevant comparative genomics defense response experience experimental study fascinate fighting genome sequencing interest medical schools microbial mutant negative affect novel pressure prevent skills success trait transcriptome sequencing transcriptomics virtual whole genome

项目摘要

ABSTRACT Bacterial lifestyles can be extremely complex, manifested most strikingly in the formation of highly cooperative multicellular structures like biofilms. Beyond the inherent basic biological interest, these complex traits have significant impacts on how bacteria relate to human health both as a defense response leading to increased drug resistance and as a source of clinically-‐‑relevant antibiotics, which are often only produced in certain social contexts. In my post-‐‑doctoral work I have used the model bacterium Bacillus subtilis to study how multicellular behaviors affect the way bacteria interact with each other. I found that B. subtilis can judge whether or not neighboring cells are close relatives, a phenomenon called kin discrimination. They do this using the extensive and diverse complement of antimicrobial molecules that each strain produces. This kin discrimination behavior creates an evolutionary pressure to diversify, resulting in so much intraspecies variation that even very closely related strains cannot coexist in their natural habitat. The first aim of this proposal will focus on the consequences of kin discrimination, specifically whether a population can better resist invasion by non-‐‑kin cells than kin. This will inform our understanding of natural microbial populations living in and around us, and how they respond to outside influences. I will also learn important technical skills involved in experimental evolution, including genome sequencing, comparative genomics, and the bioinformatic and programming skills inherent to working with large genomic datasets. The second aim seeks to gain a better understanding of the diversity lurking within the B. subtilis species by examining three routes of evolutionary change: amino acid substitutions, gain/loss of entire genes, and changes in gene transcription. By looking across multiple strains in multiple multicellular contexts, I will be able to see which of these changes is most common in early strain divergence and which genes are under the most pressure to change. This will generate a catalog of evolutionary information that will be useful for many years and open many avenues of research for my own independent lab. The techniques involved, such as RNA sequencing and bioinformatic analyses, will be invaluable additions to my skillset. The third aim of this application will examine the generality of my findings in other bacteria. Given that B. subtilis use antibiotic molecules to recognize each other, I will look in the phylum of bacteria that produces the majority of approved antibiotics: Actinobacteria. Examining intraspecies interactions can help shed light on the evolution of antibiotic production and how best to mine for clinically relevant molecules. I will investigate the ability of the Actinobacteria Streptomyces to discriminate kin from non-‐‑kin, and whether this is mediated through antibiotic diversity. This project will be my introduction to Actinobacteria, with the long-‐‑term goal of studying other aspects of their fascinating multicellular lifecycle. The training I will continue to receive under Dr. Roberto Kolter at Harvard Medical School will give me a great foundation of microbiology experience on which to build my career. HMS provides a number of advantages that will facilitate my advancement, including core sequencing facilities, bioinformatic resources, and courses dedicated to career development. Additionally, I will receive specialized training from experts in the fields of microbial genomics and Actinobacteria biology to accomplish the goals of this proposal and broaden my development as a scientist. The knowledge and techniques I will acquire under this award will be instrumental in obtaining my career goals and becoming an effective independent investigator.

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