Characterization of host genes shaping gut microbiota structure and function
Michael Shapira, Professor
Integrative Biology
Closed. This professor is continuing with Spring 2024 apprentices on this project; no new apprentices needed for Fall 2024.
Animal microbiotas are increasingly recognized as essential for host health. The gut microbiota is the richest, and was shown to contribute to diverse host functions. Perturbations in microbiota composition are associated with human disease, raising interest in manipulating the microbiota to promote healthier living or treat pathology. However, current understanding of the factors that shape microbiota composition is still lacking. Studies in vertebrates characterized the effects of diet on microbiota composition, but much less is known about the role of genetic factors, due to high inter-individual variability attributed to genetic heterogeneity. As an alternative, C. elegans enables work with genetically homogenous populations, averaging-out inter-individual variation to discern gene effects. We have established C. elegans as a new model for studying host-microbiota interactions, identifying a reproducible gut microbiota, with commensals that enhance host development and immunity. Our results demonstrate significant contributions of host genetics to shaping of microbiota structure and function and to preferential colonization by beneficial commensals, and identified a role for TGFbeta signaling in controlling abundance of a beneficial Enterobacter commensal, preventing pathogenic dysbiosis. The goal of the current project is to use worm mutants raised either on synthetic environmental microbiotas or in compost microcosms to identify and characterize host genes that shape microbiota composition and function.
Role: The student(s) chosen for this project will work with a postdoc, or a graduate student, to examine the role of genes identified through RNAseq analysis as potentially interacting with microbes, for effects on microbiota composition. They will learn worm biology, and will work with different worm mutants. They will also learn to grow and work with various soil bacteria. They will take part in analyses that will include one or more of the following techniques: qPCR measurements of microbiota size and composition, NextGen 16S rRNA sequencing to determine community composition, and analyses of fluorescent signal in worms colonized with tagged bacteria, or alternatively, in worms expressing fluorescent reporters of host gene expression and proteostasis.
Qualifications: We seek candidates who are interested in basic science. They should have solid understanding of molecular biology (gene expression, PCR, and the like) but also an interest in evolutionary biology. pre-requisite courses are Bio1A and Bio1B, but good understanding of topics covered by these courses obtained from other sources will be fine (provided that the knowledge is there, not just the credentials). Students are also expected to be able and willing to read from the primary scientific literature - to understand the overall gist of a scientific paper and to be able to seek (by asking, or in any other way) more information about the topic and methods.
Hours: 12 or more hours
Biological & Health Sciences Engineering, Design & Technologies