Adaptation to the nutritional environment is an ancient mechanism required for the survival of life on both the cellular and organismal level. The function of key metabolic tissues such as fat in sensing and responding appropriately to dietary nutrients is critical to the maintenance of health. Diet-derived metabolites can act as powerful signals to adjust cellular behaviour. Importantly, specific metabolites within the nucleus form epigenetic tags that control gene expression.
Our work aims to provide fundamental insights into the role of nuclear metabolism in ageing and metabolic syndrome (obesity and type 2 diabetes). We use innovative techniques to investigate metabolite signals linking diet and epigenetic regulation. Compartmentalisation of metabolites within cells means that their function is highly dependent upon their subcellular location. We have developed cutting-edge liquid chromatography-mass spectrometry (LC-MS) based methods for metabolomic analysis of subcellular compartments. This novel approach has revealed distinct regulation of metabolism within the nucleus, which cannot be inferred from typical methods that use whole cell analysis. We apply these techniques to investigate strategies for targeted dietary and metabolic interventions in cell and rodent models.
QUANTITATIVE SUB-CELLULAR ACYL-COA ANALYSIS USING SILEC INTERNAL STANDARDS REVEALS DISTINCT METABOLIC REGULATION OF THE NUCLEUS
Sophie Trefely, Katharina Huber, Joyce Liu, Michael Noji, Stephanie Stransky, Jay Singh, Mary T. Doan, Claudia D. Lovell, Eliana von Krusenstiern, Helen Jiang, Anna Bostwick, Hannah L. Pepper, Luke Izzo, Steven Zhao, Jimmy P. Xu, Kenneth C. Bedi Jr, J. Eduardo Rame, Juliane G. Bogner-Strauss, Clementina Mesaros, Simone Sidoli, Kathryn E. Wellen, Nathaniel W. Snyder
Molecular Cell 1, 1, 22 Nov 2021
COMPARTMENTALISED ACYL-COA METABOLISM AND ROLES IN CHROMATIN REGULATION.
Trefely S, Lovell CD, Snyder NW, Wellen KE
Molecular metabolism, 38, 1, , 08 2020
SUBCELLULAR METABOLIC PATHWAY KINETICS ARE REVEALED BY CORRECTING FOR ARTIFACTUAL POST HARVEST METABOLISM.
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
Molecular metabolism, 30, 1, , 12 2019