PhD position 7: Regulation of smooth muscle cell phenotype switching by tissue factor pathway inhibitor (Maastricht/Mainz)

We offer a PhD position for biomedical doctoral students at the School for Cardiovascular Disease in Maastricht (Maastricht, Netherlands) and the Center for Thrombosis and Hemostasis (Mainz, Germany). As this project is part of the MSCA ITN “Thrombo-Inflammation in Cardiovascular Disease” (TICARDIO), you will be trained in an international, interdisciplinary joint doctoral degree program striving to train the next generation of biomedical researchers. Your PhD project will be supervised by Prof. Dr. Tilman Hackeng in Maastricht and by Prof. Dr. Philip Wenzel in Mainz. Furthermore, research visits at TRON (Mainz, Germany) offer you the opportunity to get insights into research in the industry.

Activities and responsibilities

Project description
Vascular smooth muscle cell (SMC) phenotype switching from a contractile to a synthetic nature is an established, but not well understood contributing pathway in the initiation and progression of atherosclerosis. Based on pilot studies, our hypothesis is that control of the quiescent state of SMC is determined by the local balance of tissue factor (TF) and factor (F)Xa inactivation by endothelial tissue factor pathway inhibitor (TFPI), and coagulation-mediated activation of the PAR1/2 receptors.
You will first determine the effects of various forms of TFPI on TF and FXa mediated SMC proliferation, and examine the PAR1/2 signalling using specific pharmacological tools. Subsequently, you will use specific morpholino oligos to knock down TFPI in SMC to determine the effects on phenotype switching. In SMC, and endothelial cells as a control, TFPI expression will be measured by ELISA and established functional thrombin generation assays. You will use genetic mouse models, which are designed to mimic specific effects of FXa regulation by TFPI on SMC proliferation. In collaboration, you will investigate the altered TFPI-specific effects on SMC differentiation and vascular remodelling, in comparison to common anticoagulation therapy using plasma samples with low/high inflammatory markers. As a control for SMC-intrinsic production of FX, mice, in which FX can be knocked-out in specific cell types, will be used, while effects of TPFI will be confirmed by using mice that cannot regulate the TF initiation complex. You will apply specific PAR blockers and antibody tools to TF to interfere on the short term with TF signalling on SMC. Several short visits to TRON for practical training in RNA technologies are part of the program.

Qualification profile

>> You have a Master degree (or equivalent) in biomedical sciences or a similar field
>> You are in the first four years of your research career and do not hold a doctoral degree
>> Your must not have resided in the Netherlands for more than 12 months in the 3 years prior to the recruitment
>> Ideally, you have experience in cell culture and with cellular and molecular biology

Benefits

>> You will be working within our international group of > 30 researchers
>> You will be involved in cutting-edge research in an interdisciplinary environment
>> You will contuct your research at two research locations
>> You will receive excellent network-wide and local training with conference participation
>> You will receive a 36 months contract with all national social security (and family allowance, if applicable) at the University Medical Center Maastricht
>> You will optain a joint doctoral degree from Universities of Marseille and Mainz, if all requirements are fullfilled

Please visit www.ticardio.eu for information about the recruitment process and all required application documents.

Application deadline: July 15, 2019

Send application to

Please visit www.ticardio.eu for information about the recruitment process and all required application documents.

While applying for the job please refer to jobvector and use the following reference number: JV-50056785

About Universitätsmedizin Mainz

Center for thrombosis and hemostasis The scientific activities of the researching physicians and scientists of the medical units of the Mainz University Medical Center are characterized by a broad content spectrum. In recent years, university medicine has been able to confirm its national and international position through a large number of excellent publications and the acquisition of...
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