An ischemic stroke is caused by a thrombus in the brain and is a major cause of morbidity and mortality, with an annual incidence of approximately 32,000 cases (with 4700 deaths) in the Netherlands (data 2019). A major component of the thrombus is the fibrin network. The stability of the thrombus is dependent on its mechanical properties and on the interaction of its fibrin scaffold with blood cells. Studies on fibrin are commonly performed using clots that are formed under static conditions. In the circulation, thrombi actually are formed under flow, with significant shear rates ranging from ~150 s-1 for venous to ~500 s-1 for arterial shear. The aim of this project is to elucidate the factors that determine the mechanical properties of the fibrin network when formed under flow. The project involves a close collaboration between the hemostasis lab led by Prof. Moniek de Maat at the ErasmusMC in Rotterdam and the biological soft matter lab led by Prof. Gijsje Koenderink at Delft University of Technology. The idea is to merge biophysical concept and techniques with expertise in hemostasis and fibrin biochemistry in order to elucidate the mechanisms that control thrombus properties, with the ambition to use this knowledge to prevent or treat thrombo-embolisms.
You will construct model thrombi from plasma and from blood cells under controlled flow conditions, in order to obtain controlled combinations of fibrin and cells (platelets and/or red blood cells). You will use confocal and scanning electron microscopy in order to quantify the clot structure both at the network and fibre scale using custom-written analysis software developed by our groups. You will study the sensitivity of the clots to fibrinolysis as a function of clot composition using intrinsic and extrinsic clot lysis assays. You will determine the elastic properties of plasma and reconstituted clots as well as aspirated thrombi from patients using nanoindenter setups that are combined with fluorescence microscopy so local variations in mechanics can be mapped onto structure. For measuring the extensibility and rupture strain, you will use a tensile tester mounted on a confocal microscope, so you can visualize the mechanism of fracture and correlate it with the local network structure and composition. Finally you will use all these techniques to measure the structure and mechanics of actual aspirated cardioembolic thrombi from stroke patients.Work environment
You will be embedded in two labs, namely the lab of Prof. Moniek de Maat at Erasmus MC (your primary base, where clots will be made and studied by microscopy and biochemical assays) and the lab of Prof. Koenderink at TU Delft (where all biophysical assays will take place). You will find an inspiring, supportive and collegial environment in both places.
The de Maat lab is a biochemical lab studying the biochemistry of hemostasis and thrombosis, with a special focus on fibrinogen characteristics. The levels and properties of fibrinogen and other coagulation factors are studied in a wide range of diseases, especially cardiovascular diseases. The de Maat lab is embedded in the department of Hematology, where clinical care and research work very closely together in understanding, amongst other, the delicate balance between bleeding and thrombosis. The hemostasis research group covers fundamental, translational and clinical research.
The Koenderink lab is an experimental biophysics lab studying the mechanobiology of cells and tissues. Our approach is to combine concepts and techniques from soft matter physics, biophysics, synthetic biology, protein engineering, and cell biology. We furthermore develop advanced measurement techniques that combine quantitative imaging with force measurements across length scales ranging from the cell/tissue level down to molecular scales. The Koenderink lab is embedded in the TU Delft Department of Bionanoscience, which focuses on the fundamental understanding of biological processes from molecule to cell. The department features an inspiring, international environment with access to state-of-the art facilities for nanofabrication, a microscopy facility, molecular/cell biology, biochemistry, and high-performance computing for image processing. Current research areas in the department include single-molecule biophysics, synthetic biology, and (quantitative) cell biology.
Before you apply please check our conditions for employment.Terms of employment
You will receive a temporary position for 4 years, with an evaluation moment after 1 year. The gross monthly salary is € 2.495,- in the 1st year and increases to € 3.196,- in the 4th year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).Information and application
For more information about this position, please contact Prof.dr. Moniek de Maat, phone number: +31(0)10 703 34 42 or e-mail: email@example.com or Prof.dr. Gijsje Koenderink, email: firstname.lastname@example.org. For queries regarding your application, please contact Anouk van Rosmalen, Recruiter, by phone number: +31 (0)6 311 350 71.
If you are excited by the thought of this position and would like to apply, please do so by using the application form on our website.
No agencies please.