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  TAPAS: TArgeting Platelet Adhesion receptors in thrombosiS - Modelling of CLEC-2 clustering and signalling


   Institute of Cardiovascular Sciences

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  Prof S P Watson, Dr N Poulter  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

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:

Modelling of CLEC-2 clustering and 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: Alacris Theranostics GmbH, Germany

Supervisory Team: Bodo Lange and Christoph Wierling (Alacris Theranostics GmbH, Berlin, Germany), Natalie Poulter and Steve Watson (Birmingham, UK), Prof Bernhard Nieswandt (University of Würzburg, Germany).

Project locations: Alcaris (Year 1, 2 and 3), University of Birmingham, UK (Year 1), University of Würzburg, Germany (Year 3)

Joint PhD Degree: University of Birmingham, UK and University of Würzburg, Germany

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/

Project details: In this project computational modelling and systems biology approaches will be used to study signal transduction pathways that control platelet activation. The role of CLEC-2 clustering and signalling in thrombosis is a subject of intense research. Here we combine omics, imaging and computational modelling to provide further insight into the key molecular processes that control CLEC-2 clustering and associated signalling/function and identify novel targets that impact on platelet regulation controlled by this receptor. A large-scale computational model of a cellular signal transduction will be employed and adapted to investigate the functional effects of perturbations to the CLEC-2-associated signalling network. The model (in the form of ordinary differential equations (ODEs)) will be systematically expanded and parameterised, and through an iterative series of simulations, predictions and experimental validation, models will be optimised and novel molecular targets identified for subsequent screening of small molecule inhibitors.

Desirable student skills: Systems Biology or Bioinformatics, Python programming skills, basic knowledge of molecular biology, familiarity with working with scientific literature, experience of Matlab.

Salary Information
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.
* http://ec.europa.eu/research/participants/data/ref/h2020/wp/2016_2017/main/h2020-wp1617-msca_en.pdf

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.

Funding Notes

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

Ogilvie, L.A., Wierling, C., Kessler, T., Lehrach, H., Lange, B.M.H.Predictive Modeling of Drug Treatment in the Area of Personalized Medicine. Cancer Informatics 14(S4) 95–103 doi: 10.4137/CIN.S19330

Schütte, M. et al. Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors. Nature Communications, 8: doi:10.1038/ncomms14262

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