Burton
Laboratory

Overview

Environmental Impacts on Health and Epigenetics

The effects of a parent’s environment on offspring, also known as intergenerational effects, play a major role in biology across species ranging from plants to humans. These effects can lead to substantial changes in the development and physiology of offspring and, in many cases, even can serve as a way of programming offspring to adapt to the environment into which they are about to be born. For example, in certain species of pea aphids, the exposure of mothers to stress causes her offspring to develop wings that allows them to fly away from stressful conditions.

Despite similar observations of a mother’s environment causing what appear to be programmed changes in offspring physiology in diverse species, including humans, most of the mechanisms underlying these intergenerational effects remain unknown. Our research aims to identify the molecular mechanisms underlying intergenerational effects with a long-term aim of understanding:

  • How common are intergenerational effects in biology?
  • What are the mechanisms that mediate different observations of intergenerational effects and are they conserved across species?
  • Can we prevent the deleterious consequences associated with intergenerational effects? Particularly those observed in humans that appear to contribute to multiple human pathologies such as Type 2 diabetes.

In addition to our work on intergenerational effects, we opportunistically use C. elegans as a model organism to answer fundamental questions in biology that are difficult to study in other systems. Recently, this has included two new projects in the lab: one on SWI/SNF chromatin remodeling and one on host-microbe interactions and their contribution to disease.

SWI/SNF chromatin remodeling

Mutations in SWI/SNF chromatin remodeling subunits are found in 20% of all human cancers and cause multiple different intellectual disability syndromes and autism. However, complete loss of SWI/SNF function is lethal even in many cell culture systems, which prevents the use of well-established genetic approaches to study SWI/SNF function that have historically be used to identify pathways that interact with and regulate SWI/SNF.

To address this, we created a new model of SWI/SNF chromatin remodeling in C. elegans and already have used this new model to identify new factors that interact with this critical epigenetic regulator. We are now investigating how these factors contribute to diseases caused by mutations in SWI/SNF subunits and if these factors could be targeted therapeutically.

Host-microbe interactions

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.

C. elegans, by contrast, can easily and cheaply be grown in the presence of a single bacterial species. We are now using this advantage 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 intergenerationally 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.

Join Our Team

The Burton Lab is seeking a postdoctoral fellow interested in researching either:

  • phenotypic plasticity and intergenerational responses to stress
  • chromatin remodeling and its association with neurodevelopmental syndromes
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  • 171 studies published from Nov. 1, 2020 to Oct. 1, 2021
  • 68 studies in high-impact journals from Nov. 1, 2020-Oct. 1, 2021
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Nick Burton, Ph.D.

Assistant Professor, Department of Epigenetics

Areas of Expertise

Epigenetics, intergenerational inheritance, C. elegans, metabolism, host-microbe interactions

Biography

Dr. Nick Burton explores how chromatin remodeling contributes to human disease and how a person’s environment can impact their health and the health of their offspring. Recently, this work has become particularly interested in the diverse ways microbes and the microbiome can influence these processes. He earned a B.S. in biology from University of Wisconsin-Madison, where he worked in the labs of both Dr. Anna Huttenlocher and Dr. Scott Kennedy. He was then awarded a graduate research fellowship from the National Science Foundation (NSF) and earned a Ph.D. in biology from Massachusetts Institute of Technology, where he studied under the mentorship of Dr. H. Robert Horvitz. As part of his dissertation work, Dr. Burton sought to develop new paradigms to study the mechanisms by which parental environment regulates offspring physiology. In 2017, he joined the Centre for Trophoblast Research at University of Cambridge as an independent Next Generation Fellow. While there, he investigated how environmental bacteria can affect development, physiology, metabolism and neuronal function of individuals and their offspring. In 2021, he joined Van Andel Institute as an assistant professor in the Department of Epigenetics.

Selected Publications

Burton NO*, Willis A, Fisher K, Braukmann F, Price J, Stevens L, Baugh LR, Reinke AW, Miska EA. 2021. Intergenerational adaptations to stress are evolutionarily conserved, stress specific, and have deleterious trade-offseLife 10:e73425.
*Corresponding author

Burton NO,Greer EL. In press. Multigenerational epigenetic inheritance: Transmitting information across generationsSeminar Cell Develop Biol.

Chandrasekaran V*, Desai N*, Burton NO*, Yang H, Price, J, Miska EA#, Ramakrishnan V#. 2021. Visualising formation of the ribosomal active site in mitochondriaeLife 10:e68806.
*Equal contribution

 Burton NO*, Riccio C, Dallaire A, Price J, Jenkins B, Koulmann A, Miska EA. 2020. Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infectionNat Commun 11:1741.
*Corresponding author

Escribano APG, Bono-Yague J, Roca M, Panadero J, Sequedo MD, Saini R, Knoelker HJ, Blanca JM, Burguera JA, Lahoz A, Canizares J, Millan JM, Burton NO, Vazquez-Manrique R. 2019. Multiple hormonal signalling pathways function cell-nonautonomously to control protein homeostasis in Caenorhabditis elegansbioRxiv.

Burton NO*, Dwivedi VK, Burkhart KB, Kaplan REW, Baugh LR, and Horvitz HR*. 2018. Neurohormonal signalling via a cytosolic sulfotransferase controls insulin sensitivity of C. elegansNat Commun 9(1):5152.
*Co-corresponding author

Burton NO, Futura T, Webster AK, Kaplan REW, Baugh LR, Arur S, Horvitz HR. 2017. Insulin-like signalling to the maternal germline controls progeny response to osmotic stressNat Cell Biol 19(3):252–257.
Featured in: Kaneshiro KR and Strome S. 2017. Inheritance of protection from osmotic stress. Nat Cell Biol
Mushegian AA. 2017. An insulin-like message from mother. Sci Signal

Burton NO, Burkhart KB, Kennedy S. 2011. Nuclear RNAi maintains heritable gene silencing in C. elegansProc Natl Acad Sci USA 108(49):19683–19688.

Guang S, Bochner AF, Burkhart KB, Burton NO, Pavelec DM, Kennedy S. 2010. Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcriptionNature (7301):1097–1101.

Cortesio CL, Chan KT, Perrin BJ, Burton NO, Zhang S, Zhang ZY, Huttenlocher A. 2008. Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadapodia dynamics and breast cancer cell invasionJ Cell Biol 180(5):957–971.

Jason Cooper, Ph.D.

Research Scientist

Lauren Dunkelberg, B.A.

Senior Administrative Assistant I

Darrick Gates, B.S.

Research Technician

Kim Nguyen, B.S.

Research Technician

Xiao Wang

Van Andel Institute Graduate School Student

Thesis project title to be determined