Burton
Laboratory

The Burton Lab has long been interested in how the environment impacts an individual’s physiology and disease susceptibility. Within this broad field, the lab focuses on understanding the molecular mechanisms that mediate two different types of environmental impacts on physiology — the impact of a mother’s environment on offspring physiology and the impact of the microbiome on physiology. Through a better understanding of these interactions, we aim to develop new ways to prevent or treat diverse human pathologies with a particular focus on metabolic diseases.

Maternal environment and its impact on offspring physiology

Adapting to environmental stress is fundamental to survival. Most organisms use dedicated stress signaling pathways to sense environmental challenges and mount tailored responses. For most of the 20^th century, it was believed that any tailored stress response elicited by such signaling pathways was confined to an individual and not passed from one generation to the next. To put it another way, each generation was thought to “reset” and start with a blank informational slate about current environmental conditions. However, there is growing evidence that some environmental information is transmitted across a generational boundary. For example, silk moths can sense summer temperatures >21°C and alter hormone signaling to oocytes, which in turn modifies future progeny metabolism in a way that protects the offspring from the onset of winter. Similar observations from diverse taxa (worms, flies, mice) support the hypothesis that animals — including mammals — can adaptively transmit certain types of information about the environment to their progeny without altering the offspring’s genome sequence.

Among the many different types of multigenerational adaptations to stress that have been reported to exist, my lab focuses on observations where maternal exposures to specific stresses leads to substantial (>two-fold) increases in offspring survival in response to the same stress. In many such cases, across diverse types of animals, these robust adaptations to stress appear to be transmittable via oocytes, like the silk moth example above. These similar findings across many different species have led my lab to hypothesize that oocytes have unique and evolutionarily conserved mechanisms to link a mother’s environment to programmed changes in offspring physiology. The long-term goal of my lab is to identify the mechanisms that exist in oocytes that can link a mother’s environment to robust and long-lasting changes in offspring physiology. We anticipate that similar effects not only exist in humans, but that our studies might explain why a mother’s environment has been linked to her offspring’s susceptibility to numerous different pathologies in human epidemiological studies.

Microbiome regulation of animal physiology

Bacteria present in a human’s gut microbiome can both promote and protect against numerous diseases. Despite these observations, studies of the molecular mechanisms by which bacteria affect physiology remain challenging in complex mammalian model microbiomes that comprise hundreds of different bacterial species. The costs of maintaining germ-free models and the difficulties of working with complex microbial communities have further complicated the use of high-throughput approaches to study host-microbe interactions in mammalian model systems.

The model animal C. elegans, by contrast, can easily and cheaply be grown in the presence of a single bacterial species. We are now using this advantage of C. elegans to rapidly profile how tens of thousands of different bacteria can affect animal physiology with a particular focus on their effects on models of human disease. This includes identifying new bacteria that modify animal physiology and identifying the mechanisms by which bacteria drive these effects. In the long-term, we anticipate that we can exploit the mechanisms by which bacteria modify animal physiology to treat human pathologies. In addition, we propose that our work will allow us to determine if similar bacterial mechanisms exist in the bacteria that colonize human microbiomes and potentially contribute to human disease susceptibility.