PhD Studentship: TAPAS: Targeting Platelet Adhesion receptors in thrombosis - The role of membrane
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:
The role of membrane microdomains in GPVI signalling
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: Mike Tomlinson and Steve Watson (University of Birmingham, UK); Angel Garcia (University of Santiago, Spain); Albert Sickmann and Robert Ahrends (Leibniz-Institut für Analytische Wissenschaften (ISAS), Germany)
Project locations: University of Birmingham, UK (Year 1 & 2), ISAS, Dortmund, Germany (Year 2), University of Santiago, Spain (Year 3)
Joint PhD Degree: University of Birmingham and University of Santiago de Compostela
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/
Signalling by receptors, such as the platelet collagen/fibrin receptor GPVI, is critically dependent on the local lipid and protein membrane environment. GPVI has been reported to localise to both lipid raft and tetraspanin membrane microdomains. However, these studies have relied on membrane-disrupting detergents to isolate GPVI, such that the native membrane environment of GPVI remains undefined. We hypothesise that GPVI signalling is dependent on its interaction with specific lipids and membrane-associated proteins, and that these are altered upon GPVI activation or in the presence of GPVI-modulating therapeutics. To address this hypothesis, we will use an emerging technology for encapsulating, purifying and characterising membrane proteins in their local membrane environment. This approach, developed at the University of Birmingham, uses styrene maleic acid (SMA) copolymers as ‘molecular pastry cutters’ to convert the plasma membrane into nanodiscs, termed SMA lipid particles (SMALPs). We will affinity-purify GPVI-containing SMALPs from resting, activated and GPVI therapeutic-targetted platelets. These will be analysed for lipid and protein content using mass spectrometry-based lipidomic and proteomic methods. This work will provide fundamental new information on the mechanism of GPVI activation and signalling.
Desirable student skills: Biochemistry, Pharmacology, Structural biology.
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.
Lee et al (2016). A method for detergent-free isolation of membrane proteins in their local lipid environment. Nature Protocols 2016 11: 1149-62.
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