Host: Universiteit Maastricht, The Netherlands
Supervisory team: Paola van der Meijden and Johan Heemskerk (Maastricht University, NL), Albert Sickmann (ISAS, Dortmund DE), Jon Gibbins and Chris Jones (University of Reading, UK)
Project locations: Maastricht University (Year 1 and 2), ISAS (Year 2), University of Reading (Year 3)
Joint PhD Degree: Maastricht University and University of Reading
Project details: In this project, a humanized alternative will be developed for in vivo mouse models of thrombosis and vascular repair to determine the roles of platelet GPVI and CLEC-2 in these processes under flow conditions. For this purpose, human vascular cells will be grown in microfluidic chips and subjected to flow with whole blood. Starting from current methods, we will investigate the modulating activities of vascular endothelial and smooth muscle cells on platelet adhesion (vascular repair) and platelet aggregation (thrombus formation) via GPVI and CLEC-2. Advanced microscopy will be used to then verify the cell activation states and compare this with platelet activation markers (Maastricht NL). The established vessel-on-a-chip models will be used to generate biological samples (micro-dissection of thrombi) for targeted quantitative platelet (phospho)proteomic analysis (Dortmund DE). After transfer of the microfluidics technology to Reading (UK), effects of GPVI inhibitors will be tested under conditions relevant for vascular repair, thrombosis and haemostasis (Reading UK).
References: Swieringa F, Baaten CC, Verdoold R, Mastenbroek TG, Rijnveld N, van der Laan KO, Breel EJ, Collins PW, Lancé MD, Henskens YM, Cosemans JM, Heemskerk JWM, van der Meijden PEJ. Platelet Control of Fibrin Distribution and Microelasticity in Thrombus Formation Under Flow. Arterioscler Thromb Vasc Biol 2016;36:692-699.
Coenen DM, Mastenbroek TG, Cosemans JMEM. Platelet interaction with activated endothelium: mechanistic insights from microfluidics. Blood 2017; 130: 2819-2828.
Desirable student skills: Biochemist, Biomedicine; analytical interest.