Host-Microbe Interactions and Aging in C. elegans

Research in our lab seeks to understand the fundamentals of host-microbe interactions in the context of the whole organism, using the powerful genetic model Caenorhabditis elegans as a model host. We focus on the role of host genetic factors in shaping gut microbiome structure and function, how gut commensals affect host immunity and host-pathogen interactions, and how aging changes all that (with special interest in the role of antagonistic pletriopy in aging). Our level of investigation spans the range between molecular mechanisms, ecological constraints and impact on evolution.




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Host factors shaping the gut microbiota and microbial contributions

We have established C. elegans a new model to study host-microbiota interactions. Bringing with it unrivaled genetic tractability, C. elegans provides the ability to use genetically-homogenous populations to average-out inter-individual variation and thus to discern shared patterns in the establishment and shaping of the gut microbiota. We are using ‘deep sequencing’ complemented with isolation of specific gut residents to understand community level processes and interactions, as well as individual contributions. C. elegans has been grown in the lab for several decades with E. coli as its sole source of food. While this greatly simplifies cultivating and working with C. elegans it left us with no knowledge about the worm interactions with microbes in its natural environment. Characterization of the worm gut microbiota thus offers us novel insights into its natural history. Using C. elegans as a model we are characterizing host factors that shape the gut microbiota, and further using the worm to interrogate contributions of gut microbe to their host - from immunity to evolution. 

Aging and the microbiome

Aging has been a topic of interest in the Shapira lab for a long time. Previous work focused on Antagonistic Pleiotropy as it was manifested in the age-dependent antagonistic contributions of the C. elegans JNK kinase homolog KGB-1. Antagonistic pleiotropy is a theme in gene/protein function that is thought to underlie the evolution of aging and the aging process itself, describing how gene variants with early-life positive effects on host fitness can be positively selected in spite of their pleiotropic late-life detrimental contributions. These days, we are focusing more on the role of the gut microbiome in host aging. Aging involves multi-tissue deterioration, including the digestive system. Changes in the gut niche affect the residing microbial community. Considering the significance of gut microbes for host health and fitness, such changes may in turn affect the host negatively and contribute to aging. Our goal is delineate these changes, understand their functional significance, and their interactions with genetic programs of aging.

The role of the gut microbiome in host adaptation to environmental toxins

Human activity and industry are responsible for wide-spread toxin contamination, including pesticides, fire retardants and many more familiar and less familiar chemicals. These represent a new, yet pervasive, selection pressure on all organisms. The animal genome may be limited in its capacity to address such novel challenges. The extensive biochemical diversity of bacteria on the other hand is well capable of helping, and indeed has been useful throught animal evolution in helping animals adapt to new niches. A new research direction at the lab uses C. elegans as a model to understand to what extent do bacteria help animal hosts adapt to environmental toxins and what may be the consequences for host health.