This Theme is based on the hypothesis that scalable network models derived from metabolic phenotyping data will allow us to identify the molecular background of clinical phenotypes, facilitating development of diagnostic methods for precision medicine, and help develop therapeutic interventions including targeted drug therapy and dietary interventions.
The Molecular Phenotyping Theme will employ an innovative combination of tissue/cell-focused analysis featuring spatially resolved analysis and established traditional metabolomics-based biomarker discovery approaches to create scalable network models of disease. Spatially resolved multi-omics analysis of tissues offers a straightforward way to map network structures in clinical samples, leading to the identification of pathways driving the disease or differentiating the various clinical phenotypes. Figure 1 exemplifies this using a simple sub-network representing a significant difference in lipid metabolism between metastatic and non-metastatic colorectal adenocarcinoma. The sub-network features phospholipids and fatty acids that show strong correlations in metastatic disease, while these correlations are negligible in localised disease. This correlation is associated with cPLA2 expression, which activates COX1/COX2 pathway via the liberation of arachidonate (Inglese-bioRxiv-2018) and leads to eicosanoid-mediated inflammation. The mechanism has been identified as a driver for cell proliferation and EMR in various epithelial cancers by us and other research groups
Key Individuals
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Professor Josephine Bunch
Theme Lead, Molecular Phenotyping -
Professor Zoltan Takats
Professor of Analytical Chemistry -
Dr Isabel Garcia-Perez
Lecturer in Precision & Systems Medicine -
Dr Jonathan Swann
Senior Lecturer in Microbiomics and Human Development -
Dr Kirill Veselkov
Lecturer -
Dr Muireann Coen
Lecturer in Metabonomics & Biochemical Toxicology -
Dr Robert Plumb
Visiting professor/Director of Global Phenotyping (Waters Corporation) -
Dr Stephen Brett
Reader in Critical Care -
Dr Tim Ebbels
Reader in Computational Bioinformatics -
Dr Toby Athersuch
Lecturer in Environmental Toxicology -
Dr. Joram Posma
Research Associate -
Professor Anthony Gordon
Chair in Anaesthesia and Critical Care -
Professor Ian Wilson
Chair in Drug Metabolism and Molecular Toxicology -
Professor John Lindon
Professor of Chemistry
