Research Overview

We are interested in the co-evolution of humans with their microbiomes. Our basic science investigates the evolutionary history of gut microbes, how they have adapted to life inside humans and how they affect human biology and health.

Microbiome Science

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Director:

Ruth Ley

Our research program aims to elucidate how gut microbial species relate to genotypic differences between human individuals, to identify bacterial and archaeal species that share an evolutionary history with humans, and to determine the molecular basis of long-term host-microbial relationships. We approach these aims with a combination of population-level observations and molecular-level investigations in the laboratory. We link inter-microbial and microbial-host interactions at the molecular scale to patterns at population and evolutionary scales. This cross-scale approach has led to the following discoveries: Key contributions of the Ley Lab: Human genetics shape the gut microbiome: Ley and colleagues challenged the…

Microbiome Genetics

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Departmental Group Leader:

James Marsh

The community of microorganisms within the human gastrointestinal tract is one of the most diverse ecosystems known, yet we currently have limited tools to unravel its intrinsic complexity. Next-generation sequencing approaches have been invaluable for the characterisation of gut microbial distribution, abundance, and evolution, but elucidating the mechanistic basis for these dynamics requires an ability to perturb the system through manipulation and testing. However, most species of the human gut microbiota are genetically untractable. We are developing novel genetic systems for non-model organisms living within the human gut….

Microbiome Bioinformatics

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Departmental Group Leader:

Alexander Tyakht

Host-associated microbial communities demonstrate remarkable diversity and dynamics while maintaining stability, reflecting their co-evolution with humans. The gut microbiome, particularly for humans, is integral to various bodily functions. We aim to understand the principles underlying its temporal stability and rapid response to external influences, as well as how the vast functional potential encoded in gut microbial genomes is realized. To address these questions, we employ algorithms, software pipelines, and statistical methods to analyze microbiome sequencing data in the context of health, disease, diet, and geography. Our approach encompasses conventional metagenomics and modified techniques such as high-throughput conformation capture (Hi-C…

Microbiome Lipid Metabolism

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Project Leader:

Stacey Heaver

Lipids are more than just structural components of membranes or energy storage in adipocytes – they form a diverse array of molecular structures that also serve bioactive roles in all kingdoms of life. Our guts are filled with microbes that synthesize their own lipids and modify lipids from their host or diet. These gut microbe-derived lipids can interact both with other bacteria and their human host, altering host metabolism, signaling, and immunity. Different bacterial species produce lipids which help them adapt to the ecological niche in which they live. Excitingly, gut bacteria exhibit a remarkable structural diversity of lipids,…

Microbiome Evolution

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Project Leader:

Hagay Enav

Infants are born germ-free and ready for microbial colonization. The first consortium of microbial colonizers can shape the growth, development, and health of the host during infancy and well into later life. As newborns mature, their diet, immune system and microbiome composition change rapidly, creating shifting selective pressures on members of the gut microbial community. These changes are expected to drive enhanced evolutionary dynamics, giving rise to new microbial traits and co-existing strains, which may, in turn, further influence the host in the years ahead. We study the evolution and ecology of the gut microbiome at high resolution, with…