Host: Universiteit Maastricht, The Netherlands
Supervisory team: Marijke Kuijpers and Johan Heemskerk (School for Cardiovascular Diseases Maastricht University, NL). Helma Rutjes (Pivot Park Screening Centre, Oss, NL), Ángel García (University of Santiago de Compostela, SP)
Project locations: Maastricht University, NL with nearby PPSC (Year 1 and 2); Santiago de Compostela, SP (Year 3)
Joint PhD Degree: Maastricht University and University of Santiago
Project details: New methods will be developed and applied for ultra-high throughput screening of platelet functions in thrombosis and haemostasis, particular in response to GPVI or CLEC-2 receptor stimulation. These methods will be employed to compare the signalling strengths (western blotting) of ligands with variable degree of receptor clustering. Calcium fluxes will be compared with physiological platelet responses (3-state detection of platelet activation) (Maastricht NL). These methods will be further developed into a robust assay for ultra-high throughput small molecule screening (1536- or 384-well plates). After a pre-screen with known small molecules, a first screen will be performed to identify inhibitors of GPVI and/or CLEC-2 responses (versus GPCR) using an existing library of small molecules (PPSC, NL). Candidate inhibitory molecules will then be further validated using the automated screening platforms at Santiago de Compostela (SP).
Desired student skills: Biochemist or Biomedicine.