Michael Shapira, Professor

Closed (1) The role of the gut microbiome in host adaptation to environmental toxins

Applications for fall 2021 are now closed for this project.

Toxins play important roles in inter-species interactions, and the ability to overcome them can open new niches. The potential of animal genomes to facilitate such adaptations is limited; instead, toxin resistance in animals is often provided by gut bacteria. Human activity and industry has dramatically increased the prevalence of environmental toxins, including antibiotics and pesticides, which represent a novel selection pressure on most if not all organisms, and can affect animal health and potentially evolution. Anecdotal evidence suggests that animals can acquire pesticide-resistance by exchanging gut symbionts for environmentally-enriched toxin-modifying bacteria. However, such short-term fitness advantages may come with a price, as changes in microbiome composition, or dysbiosis, are associated with long-term detrimental consequences and pathology. Using C. elegans as a model host, we study the roles of environmentally-acquired gut bacteria in host adaptation to toxic antibiotics, the mechanisms enabling productive gut-environment exchanges, and the long-term consequences of changes in the gut microbiome for host health and lifespan.
We seek an enthusiastic and motivated undergrad to take part in this project

The undergrad working on these projects will be trained in basic lab techniques such as media preparation, maintenance of bacteria and nematodes, preparation of DNA samples for genetic sequencing, and possibly microscopy. Furthermore, we will provide relevant papers from the scientific literature and guidance on how to read and interpret scientific writing. We will expect apprentices to commit to learning about the experimental system and lab techniques, engaging in our research, attending our weekly lab meetings, and helping to move our projects forward. While the URAP program is a one semester commitment, we seek an undergrad who would be interested in continuing to develop projects and skills in the lab in future semesters as well.

Day-to-day supervisor for this project: Dan Kim, Ph.D. candidate

Qualifications: Pre-requisites: Bio1A/Bio1B; students should be able and willing to read and understand scientific literature (especially research articles) to a level that will allow them to understand the general concepts described in the project description. Sophomores or Juniors.

Weekly Hours: 12 or more hours

Related website: http://ib.berkeley.edu/labs/shapira/

Closed (2) Characterization of host genes shaping gut microbiota structure and function

Applications for fall 2021 are now closed for this project.

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.

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., Post-Doc

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.

Weekly Hours: 12 or more hours

Related website: http://ib.berkeley.edu/labs/shapira/

Closed (3) Age-dependent changes in gut microbiota composition and their significance for host aging

Applications for fall 2021 are now closed for this project.

Aging involves a multi-system physiological deterioration. In addition to affected tissues, and likely as a consequence, aging also affects the gut microbiota, an extensive microbial community which contributes to diverse host functions. Imbalances in microbiota composition, or dysbiosis, are often associated with pathology, and recent reports indicate that aging-dependent dysbiosis exacerbates aging phenotypes. Potentially, microbiotas could be rebalanced to ameliorate aging; however, to achieve this, better understanding is required of the reciprocal interactions between host aging and the altered microbiota. C. elegans is a valuable model for aging research thanks to its short lifespan. We have recently established it also as a model for microbiome research, offering advantages unmatched in vertebrate models, including the ability to work with genetically homogenous populations, which average-out inter-individual variation to better discern shared patterns. We have previously shown that C. elegans harbors a characteristic and persistent gut microbiota, shaped (both structurally and functionally) by host genetics. Furthermore, we found that worms undergo extensive remodeling of their microbiota during aging, including an Enterobacteriaceae bloom, reminiscent of the overgrowth seen in aging humans. The current project will take advantage of the C. elegans model to establish causative relationships between host aging and microbiota composition, and to determine functional significance of age-altered commensals to aging, examining effects on motility, immunity, proteostasis and lifespan.

The student(s) chosen for this project will work with a postdoc, or a graduate student, to examine changes in microbiota composition during worm aging. 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, analyses of fluorescent signal in worms colonized with tagged bacteria, or alternatively, in worms expressing fluorescent reporters of host gene expression and proteostasis, and survival analyses, testing host susceptibility to pathogens., Graduate Student

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 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.

Weekly Hours: 12 or more hours

Related website: http://ib.berkeley.edu/labs/shapira/