PhD position 12: Deregulated transcriptome 3’ end diversification affecting thrombo-inflammation (Mainz/Maastricht)

We offer a PhD position for biomedical doctoral students at the Center for Thrombosis and Hemostasis (University Medical Center Mainz, Germany) and the School for Cardiovascular Disease in Maastricht (CARIM, Netherlands). 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. Sven Danckwardt in Mainz and by Dr. Elisabetta Castoldi in Maastricht. Furthermore, you will get the opportunity to get insights into research in the industry at Bayer (Wuppertal, Germany, Dr. Stefan Heitmeier).

Activities and responsibilities

Project description
The diversification of the transcriptome evolved as a global and evolutionarily conserved layer of gene regulation. In this project, we want to illuminate the pathology of thrombo-inflammation by exploring how transcriptome 3’ end diversification (TREND) affects components of blood coagulation and thereby causes perturbances of the hemostatic system. In a proof-of-concept study, we want to explore whether TREND of blood coagulation components can be exploited therapeutically to correct deregulated blood coagulation.
By applying high-throughput TRENDseq based sequencing, you will screen which blood coagulation factor mRNAs are regulated by. In cell cultures, specific properties of TREND-affected coagulation factors will be examined. You will analyze how TREND of relevant coagulation factor RNAs is associated with a procoagulant phenotype in mice. To this end, the mouse phenotype will be compared with respective TREND isoforms expressed under inflammatory conditions. At the second host CARIM, you will study how main TREND-regulated mRNAs encoding coagulation proteins can be used as future therapeutic targets. This work involves specific silencing of regulated TREND sites, by using morpholino-based antisense RNA therapies, which have already successfully been applied to correct aberrant splicing in factor V deficiency. In connection to ESR11, the fibrinogen gamma-chain gene, which produces two alternatively spliced mRNAs with different 3’-ends, each regulated by inflammatory stimuli, will serve as a prototype.

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 Germany for more than 12 months in the 3 years prior to the recruitment
>> Ideally, you have experience in molecular biology, cell culture work, animal work, a strong background and interest for gene regulatory mechanisms and a profound knowledge of the hemostatic system

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 the University Medical Center Mainz
>> You will optain a joint doctoral degree from Universities of Mainz and Maastricht, if all requirements are fulfilled

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.

Application deadline: July 15, 2019

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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