How does host genome determine the microbiome?
Name of applicant
Jack Howe
Institution
University of Oxford, United Kingdom
Amount
DKK 1,831,485
Year
2020
Type of grant
Reintegration Fellowships
What?
Like all other animals, we carry trillions of bacteria in and on our bodies, collectively called the microbiome. These bacteria, however, are not just passive hitchhikers, and have profound implications for organismal health and function. They enable animals to exploit novel food sources, they influence animal behaviour and hibernation patterns, and associations with bacteria have been linked to the evolution of multicellular animals. Controlling the composition of the microbiota is therefore paramount. This project aims to establish how animals evolved to control which bacteria comprise the microbiome, and how those bacteria have evolved for a life with animals, by establishing a uniquely tractable model system for the study of host-microbiome interactions: the planarian flatworms.
Why?
The composition of the microbiome is determined by complex interactions between the host's genome and environment, as well as interactions among the many bacteria. While it is clear that the host's environment is important, the role of the host itself is still hotly debated. Unpicking the effects of each component is difficult, because manipulating one aspect inadvertently impacts all others. The planarian flatworms, however, promise a novel approach for studying host-microbiome interactions that can resolve this impasse. They possess a unique stem cell system which confers them with remarkable regenerative abilities that, unlike other systems, enable manipulation of host-genotype in living animals and thereby isolation of the role of the host in determining the microbiome composition.
How?
This project will exploit the planarians' unique stem cell system, together with cutting-edge sequencing technologies, to isolate the role of the host genome in controlling the microbiome. By transplanting stem cells among individual worms, we will transform the genetic identity of the host around their microbiome and follow how this affects the bacteria that comprise it. We will complement this by constructing artificial planarian microbiomes and testing how this affects worm traits-their ability to fight infections, or to adapt to novel conditions.