Research

Research in the Sharpton Lab is broadly directed towards ascertaining how the human microbiome, especially the gut microbiome, relates to health. We specialize in the development and application of high-throughput computational and statistical tools that characterize microbiome biology, and investigate how microbiomes are associated with host health, environmental exposures, and animal evolution. We aim to develop testable hypotheses about how humans and their microbiome interact, and strive to understand the evolutionary and ecological processes that influence community assembly, maintenance, and function within a host. Ultimately, this knowledge will be used to discover disease mechanisms, identify predicative and diagnostic biomarkers of disease, and develop tools to treat disease through manipulation of the microbiome. A brief summary of our focal research projects follows. All of the data resources and software that we develop are freely available.

 

Inference of metagenome structure and function

Microbiomes are increasingly studied through the analysis of metagenomes, which are generated by collectively applying high-throughput DNA sequencing to all genomes present in a microbial community. While rich in information, metagenomes are complicated to interpret due to the diversity and volume of data generated. We have developed several cutting-edge algorithms and software resources that analyze metagenomes and quantify the taxa that comprise the community and the biological functions encoded in their metagenomes. We maintain these tools through an open access software repository, and are actively developing new analytical resources that clarify how microbiomes operate.

 

 The role of the gut microbiome in inflammation-based chronic diseases

Mouse ModelsChronic diseases such as obesity, type 2 diabetes, and inflammatory bowel disease have been rapidly rising over the past several decades, but researchers aren’t entirely certain as to why. Several studies have implicated the gut microbiome in the development and severity of these diseases, including our work which finds that microbiome metabolic pathways differ between healthy people and those afflicted with Crohn’s disease. With our collaborators, we are using mouse models of inflammation-based chronic diseases, including metabolic syndrome, type 2 diabetes, and Crohn’s disease, to determine how the microbiome acts to influence disease state. Our work will identify microbiome-mediated mechanisms of disease, diagnostics, and potential therapeutics.

 

 

The impact of environmental health on microbiome structure and function

ZebrafishDisrupting the microbiome can perturb animal homeostasis and yield disease. As part of our efforts to prevent disease, we should comprehensively catalog those factors that disrupt the microbiome. We posit that many of the diverse array of environmental chemicals to which animals are exposed, including diet, drugs, and toxicant, can perturb the microbiome and yield chronic disease in its host. To enable rapid screening of the effect of various chemical exposures on the microbiome, we worked with our collaborators at the Sinnhauber Aquatic Research Laboratory to develop a high-throughput system that quantifies the impact of chemical exposure on zebrafish physiology and its gut physiology. Those chemicals that produce microbiome-mediated disease in zebrafish and will subsequently be investigated in mice and humans. Our work will clarify environmental-health mediated disease mechanisms and improve disease prevention efforts.

 

The ecological and fitness effects of the gut microbiome

SalmonWhile extensive research has clarified the importance of the gut microbiome to animal health, there has been relatively little exploration of the role the microbiome plays on animal ecology and fitness. For example, perturbation to the gut microbiome is often associated with disease. As a result, natural selection may serve to act on the gut microbiome and ecological conditions that perturb it may alter the fitness landscape of an animal population. To obtain insight into these questions, we are using the Aquatic Animal Health Laboratory to investigate how climate-change driven changes in water temperature impact the gut microbiome of Pacific salmon and its ability to resist infection by a major intestinal parasite, Ceratonova shasta. Our work will clarify the role that the gut microbiome plays in maintaining salmon fitness, provide insight into how climate change may impact fisheries, and identify components of the microbiome that should be actively preserved to mitigate these impacts.

 

Gut microbiome evolution

Tree of LifeComponents of the gut microbiome appear to be heritable among humans and even shared across animal species. This suggests that the gut microbiome may diversify in association with animal evolution and potentially co-evolve with animals. To clarify whether there are evolutionary signatures in the gut microbiome, we are using high-throughput DNA sequencing to interrogate microbiomes from an evolutionarily diverse set of animals. By applying comparative evolutionary techniques, we will identify components of the gut microbiome that have co-diversified with animals, indicating that they interact with animal physiology. This work will identify specific aspects of the microbiome that are important to maintaining animal health, clarify the evolutionary mechanisms that influence microbiome diversification, and amend how we think about animal evolution.