PhD position 11: Alternative splicing in the regulation of thrombo-inflammation (Maastricht/Marseille)

We offer a PhD position for biomedical doctoral students at the School for Cardiovascular Disease in Maastricht (CARIM, Netherlands) and the Center for CardioVascular and Nutrition research (C2VN at Aix-Marseille Université, France). 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 Dr. Elisabettea Castoldi in Maastricht and by Prof. Dr. Pierre Morange in Marseille. Furthermore, a research stay at TRON (Mainz, Germany, Dr. Tim Beissert) offers you the opportunity to get insights into research in the industry.

Activities and responsibilities

Project description
Alternative splicing of key coagulation factors has been shown to result in a markedly different activity of these factors and plays a pivotal role in regulating the haemostatic balance. This includes a splicing variant of fibrinogen (fibrinogen γ’) which is associated with an increased risk of venous thrombosis. Thus, we hypothesize that genetic variants and splicing isoforms of coagulation factors are associated with an increased thrombosis risk and their detection in the blood plasma may reveal a procoagulant phenotype.
You will search for associations between genetic markers in common variants of coagulation-related genes, levels of coagulation factors/inhibitors including their splicing variants, and the risk of thrombosis in existing patient cohorts. The cohorts employed are the SCACORO study, the AtheroGene study, and MARTHA+MARFAST study. Subsequently, using cell cultures and biochemical assays in plasma, the molecular mechanisms of the identified associations with a focus on the candidate genes F5 (factor V), TFPI (tissue-factor pathway inhibitor) and FGG (fibrinogen gamma-chain) will be studied. You will then identify the genetic determinants of factor V-short (FV-short) – a carrier of TFPIα – by genotyping and factor/activity measurements in patient plasma, using minigene models and RT-PCR. You will investigate the possible mechanisms by which alternatively spliced fibrinogen γ’ affects the risk of thrombosis. Plasma from patients with low fibrinogen γ’ levels and high fibrinogen γ’ levels will be compared by thrombin generation, rotational thromboelastography, and fibrin flow tests.

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 an affinity for lab work and possess analytical skills

Benefits

Benefits of working in an ITN
>> 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 and the site of an industry partner
>> 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 CARIM.
>> You will optain a joint doctoral degree from Universities of Maastricht and Marseille, if all requirements are fullfilled

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

Application deadline: July 15, 2019

Send application to

How to apply
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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