ESR 11: Integrating omics, functional datasets and microscopy to predict thrombosis and haemostasis

Host: Leibniz-Institut Fur Analytische Wissenschaften-ISAS, Germany

Supervisory team: Robert Ahrends and Albert Sickmann (ISAS, Dortmund, DE), Steve Watson (University of Birmingham, UK); Johan Heemskerk and Rachel Cavill (School for Cardiovascular Diseases, Maastricht University, NL)

Project locations: ISAS, Dortmund, DE (Year 1), University of Birmingham, UK (Year 2); Maastricht University, NL (Year 3); ALACRIS, Berlin, DE (beginning Year 3)

Joint PhD Degree: University of Birmingham and Maastricht University

Project details: The project aims to develop innovative, predictive models of thrombosis and haemostasis by integrating large data sets. We will use diverse multiparameter data sources to identify rate limiting steps in thrombosis. The data will be obtained from platelet (phospho)proteomics, lipidomics, metabolomics experiments (Dortmund), and matched with platelet signalling and super-resolution microscopy (Birmingham), as well as functional vessel-on-a-chip and thrombosis studies (Maastricht). Quantitative omics experiments using the novel SIMPLEX methods1 will be carried with platelets from mice with GPVI deficiencies or alterations, with extensive validation in human platelets. Early events in signalling will be unravelled by specific GPVI ligands and/or inhibitors.2 A systems biology approach will be applied in order to identify and integrate major hubs and rate-limiting steps in GPVI signalling. Overall, this project will clarify how multi-omics changes in GPVI signalling determine platelet functional responses in micro- and macroscopic thrombosis.

References: Coman C, et al. R. Simultaneous metabolite, protein and lipid extraction (SIMPLEX): a combinatorial multimolecular omics approach for systems biology. Mol Cell Proteomics, 2016.

Beck F, et al. Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition. Blood, 2017.

Desirable student skills: (analytical) chemistry, bioinformatics.

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