PhD Studentship: TAPAS: Targeting Platelet Adhesion receptors in thrombosis - Regulation of GPVI cl
The TAPAS, European Joint Doctorate (EJD), Innovative Training Network, funded by the European Commission under the H2020 research programme, is seeking an Early Stage Researcher (ESR) to undertake a PhD in: Regulation of GPVI clustering: role of the cytoskeleton
TAPAS is highly intersectoral and multi-disciplinary programme of work which will tackle the problem of thrombosis (blood clots) which can lead to heart attack and stroke and contributes to an estimated 40% of cardiovascular deaths in the EU, and over €200 billion a year to the EU economy. Current therapy in the prevention of arterial thrombotic events includes drugs that suppress the function of a specialised blood cell called a platelet. Platelets are necessary for preventing bleeding, but their unregulated or inappropriate activation can lead to thrombosis. Whilst suppressing platelet function is effective in a large proportion of patients, it is not perfect and some patients experience further thrombotic episodes, bleeding problems or even death.
The research will combine innovative approaches and develop new expertise to identify, understand and test new targets on blood platelets for the selective prevention and treatment of thrombotic diseases.
Host: University of Birmingham, UK
Supervisory team: Natalie Poulter and Steve Watson (University of Birmingham); Bernhard Nieswandt (University of Würzburg)
Project locations: University of Birmingham, UK (Year 1 & 3), University of Würzburg, Germany (Year 2), University of Rijeka, Croatia (2 months in Year 1)
Joint PhD Degree: University of Birmingham and University of Würzburg
This PhD will require the ESR to split their time between institutions and be mobile across the network. As part of the ITN network, you will have access to the various training activities organized by the network and to secondments at partner institutions.
For further information please see the TAPAS website: https://more.bham.ac.uk/tapas/
Apply here: https://more.bham.ac.uk/tapas/vacancies/
The platelet receptor GPVI has been identified as a promising anti-thrombotic target so it is important to understand how GPVI signalling is regulated. Interaction with its ligands causes GPVI to cluster and this can be visualised with advanced microscopy techniques1. The actin cytoskeleton is known to play a role in receptor clustering in many cell types but its role in GPVI clustering has not been studied. Work using knock mouse models of a small GTPase Rac1, which is involved in regulating actin, has shown that Rac1 is required for proper GPVI signalling and thrombus formation2. We hypothesise that this is through regulation of GPVI clustering.
In this project we will investigate the role Rac plays in GPVI clustering in human platelets using Rac inhibitors and single molecule microscopy techniques (Birmingham). Studies will be extended into mouse platelets using knock out mouse models of Rac1 and other cytoskeleton proteins (Würzburg). Biochemical techniques will be used to investigate how this influences downstream signalling events. The effect on clustering of novel biologics or small molecule inhibitors generated by other ESRs in TAPAS will be tested.
Training in alternative methods for studying receptor-cytoskeleton interactions will be received through a secondment to University of Rijeka, Croatia.
Desirable student skills: Biophysics, Cell biology, Biochemistry, an interest in microscopy, an aptitude for maths/coding/computer science, willingness to work with animal models.
Living Allowance: This refers to the basic, gross amount for the benefit of the researcher to be paid to the researcher in monthly instalments. For this MSCA call launched in 2016-2017, the amount for an ESR is €3,110 per month (€37,320/year – 100%). This amount is then adjusted through the application of a country correction coefficient to the living allowance of the country in which the researcher will be recruited.* The final amount will not change in case of secondments to another beneficiary or partner organisation.
Mobility Allowance: All eligible researchers recruited within an ITN are entitled to receive this allowance. It contributes to the mobility related expenses of the researcher. The amount of the mobility allowance for the calls 2016-2017 amounts to €600 per month.
Family Allowance: A family allowance of €500 per month will be paid should the researcher have family, regardless of whether the family will move with the researcher or not.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 766118.
ITN Mobility Rule: You must not have resided or carried out your main activity in the host country for more than 12 months in the last 3 years. Compulsory national service and/or short stays such as holidays are not taken into account.
Early-Stage Researcher: You shall be in the first four years (full-time equivalent research experience) of your research career and must not yet have been awarded a doctoral degree.
References: Poulter et al (2017). Clustering of glycoprotein VI (GPVI) dimers upon adhesion to collagen as a mechanism to regulate GPVI signaling in platelets J Thromb Haemost. 15(3):549-564
Pleines et al. (2009). Rac1 is essential for phospholipase C-γ2 activation in platelets Pflugers Arch – Eur J Physiol, 457: 1173
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