PROJECT
SUPERVISORS

Project Supervisor

Sophie Trefely

Background

I completed my undergraduate and PhD training in Australia earning a BMedSci(Hons) at UNSW in 2008 and a PhD studying insulin action with David James at the Garvan Institute of Medical Research in 2015. Inspired by breakthroughs on the role of metabolites as signaling molecules, and metabolomics techniques, I moved to the University of Pennsylvania (USA) to train under Kathryn Wellen and Nathaniel Snyder.

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I studied the impact of nutrient metabolism on metabolic tissues and diseases and developed methods to analyse subcellular metabolism via liquid chromatography-mass spectrometry. This work revealed distinct regulation of metabolism within the nucleus, which cannot be inferred from typical methods. I established my research group at the Babraham Institute (UK) in January 2022 as part of the Epigenetics and Signalling Programmes.

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Research

My lab studies metabolic pathways and metabolite signals that link nutrients to the epigenome. We aim to understand how nuclear metabolism supports cell identity. Diet-derived metabolites can act as powerful signals to adjust cellular behavior. Importantly, specific metabolites within the nucleus form epigenetic tags that control gene expression. Despite metabolites being critical for epigenetic regulation, how specific metabolites occur within the nucleus and their role in establishing and maintaining cell identity remain unclear.

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We study the dynamic relationship between metabolites in the nucleus and their corresponding chromatin modifications. Our lab has established and continues to develop methods for nuclear-specific metabolite analysis that combine liquid chromatography-high resolution mass spectrometry (LC-HRMS) and biochemical techniques. We use multiple approaches, including sequencing, to study the regulation, genetic location, and function of metabolically-dependent chromatin modifications. We apply these techniques in cell and rodent models to understand the mechanisms connecting diet, metabolic disease, nuclear metabolism, and epigenetic regulation.

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Publications

Soaita I, Megill E, Kantner D, Chatoff A, Cheong YJ, Clarke P, Arany Z#, Snyder NW#, Wellen KE#, Trefely S#. Dynamic protein deacetylation is a limited carbon source for acetyl-CoA-dependent metabolism. J Biol Chem. 2023 Jun;299(6):104772. doi: 10.1016/j.jbc.2023.104772.

Trefely S, Huber K, Liu J, Noji M, Stransky S, Singh J, Doan MT, Lovell CD, von Krusenstiern E, Jiang H, Bostwick A, Pepper HL, Izzo L, Zhao S, Xu JP, Bedi KC Jr, Rame JE, Bogner-Strauss JG, Mesaros C, Sidoli S, Wellen KE, Snyder NW. Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation. Mol Cell. 2022 Jan 20;82(2):447-462.e6. doi: 10.1016/j.molcel.2021.11.006.

Trefely S, Lovell CD, Snyder NW, Wellen KE. Compartmentalised acyl-CoA metabolism and roles in chromatin regulation. Mol Metab. 2020 Feb 14:100941. doi: 10.1016/j.molmet.2020.01.005.

Trefely S, Liu J, Huber K, Doan MT, Jiang H, Singh J, von Krusenstiern E, Bostwick A, Xu P, Bogner-Strauss JG, Wellen KE, Snyder NW. Subcellular metabolic pathway kinetics are revealed by correcting for artifactual post-harvest metabolism. Mol Metab. 2019 Dec;30:61-71. doi: 10.1016/j.molmet.2019.09.004.