Collaborative Research: Prophages and how they manipulate model microbiomes

合作研究：原噬菌体及其如何操纵模型微生物组

• 批准号: 2226051
• 负责人: Jeffrey Gralnick
• 金额: $ 49.75万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2226051&HistoricalAwards=false
• 关键词: Collaborative; Research; Prophages; how; they

The animal gut is colonized by a community of microbes, the gut microbiome, that can impact health and well-being. The most abundant microbes in the gut are bacteria, and they are metabolically active and most of them are friendly or benign to the animal host. Like most organisms, bacteria also get infected by viruses, and these are known as bacteriophages or phages. One version of these phages is known to infect bacteria and integrate into their DNA as prophages, remaining in what is thought to be a dormant state. However, because of the genes they carry or the location of their integration, prophages can impact the behavior of bacteria and can increase their resistance to antibiotics. Despite the increased recognition of how animal microbiomes impact health, little is known about how prophages influence the structure and function of animal microbiomes. This project will leverage two model systems, an invertebrate chordate, Ciona robusta, and a vertebrate, the zebrafish Danio rerio to identify how prophages affect animal microbiomes. The project will integrate genetic, predictive modeling, and experimental approaches to study the biology and ecology of prophage influence on animal microbiomes. Data from this study will contribute to the understanding of factors shaping homeostasis within the gut of animals. Other broader impacts of this project include training and mentoring of students, some from underrepresented communities, in research on microbiology, bioinformatics, and immunology. The investigators will engage K-12 students with activities such as “Skype-a-Scientist” and an oceanography camp for girls. Additionally, the investigators will perform outreach to the general public at science festivals, museums, and farmer markets. Most animals form essential relationships with bacteria. Bacteriophages (or ‘phages’) are viruses that infect these bacteria, and it is well established that through lysis, ‘lytic’ phages restructure bacterial communities while ‘temperate’ phages can integrate into bacterial genomes as ‘prophages,’ transforming their hosts into ‘lysogens’. Integration into bacterial genomes can influence nearby genes, while other viral genes or regulatory regions can influence bacterial physiology and fitness in a process referred to as ‘lysogenic conversion.’ However, compared to our significantly improved understanding of the diverse roles of bacteria in animal microbiomes, the impact of prophages on these communities remains largely overlooked. This proposal will test the hypothesis that prophages shape the biology of their bacterial hosts and drive structural and functional changes in animal microbiomes. Utilizing a combination of bacterial genome sequencing and molecular genetics while integrating ecological modeling and experimental approaches, the investigators will study the biology and ecology of lysogens in the microbiomes of two powerful model systems, the tunicate Ciona robusta, and the zebrafish Danio rerio. Specifically, the investigators will characterize prophage distribution and location in genomes of cultivated heterotrophs from model microbiomes, determine the influence of prophages on bacterial host properties (swimming, biofilm formation, growth / physiology) via targeted prophage deletion mutagenesis, and examine the role of prophages in shaping colonization and influencing the stability of the gut microbiome in vivo and in silico. This research may reveal general principles by which prophages directly affect microbial function, leading to both major and minor changes in animal microbiomes.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.

在最丰富的微生物中，最丰富的微生物中最丰富的微生物是细菌，它们具有代谢活性，大多数人像大多数生物体一样自由地或良性。 。微生物会影响健康，对动物微生物组的预言结构和功能知之甚少。对动物的稳态的预言调查人员将在科学节，博物馆和农贸市场上向公众表演。 “预言”，溶解度可以影响Earby基因，而其他病毒基因或野生性基因的效率和适应性在被称为“溶裂性的过程中”。在动物微生物中，预言对E的影响仍然忽略了动物微生物的结构变化。两个强大的模型，即Icate Ciona Robusta和斑马鱼Danio Rerio。塑造定殖的预言和体内肠道微生物组的稳定性，而在硅中直接影响了微生物的功能，从而导致动物微生物的重大和较小变化。通过使用Toundation的智力功绩优异Meriter的评估来支持的支持影响审查标准。