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Modelling of CLEC-2 clustering and signalling


Institute of Cardiovascular Sciences

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

About the Project

We invite applications for a PhD Studentship in Molecular Biology and Systems Biology Modelling as part of the Marie Sklodowska-Curie Innovative Training Network (ITN) and European Joint Doctorate (EJD).

Become part of an outstanding, interdisciplinary and international Research Network:

TAPAS (Targeting Platelet Adhesion Receptors in Thrombosis) is a Marie Sklodowska-Curie Innovative Training Network (ITN) European Joint Doctorate (EJD). TAPAS is a consortium of 7 European countries, led by the University of Birmingham, along with 7 beneficiaries and 6 partners from the UK, Ireland, Germany, Spain, Netherlands, Croatia and Hungary. TAPAS will train a uniquely-qualified cohort of 15 Early Stage Researchers (ESRs) in a highly multi-disciplinary programme of work.

The project 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. 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. The research conducted in TAPAS 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.

We are offering an exciting opportunity for an ESR to be part of TAPAS and undertake a PhD in:

Modelling of CLEC-2 clustering and signalling

Host: Alacris Theranostics GmbH, Germany

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

Project locations: Alacris (Berlin, Germany), University of Birmingham, (UK), University of Würzburg (Germany)

Start of project: 1st September 2018

Desirable skills:
Systems Biology or Bioinformatics, Python programming skills, basic knowledge of molecular biology, familiarity with working with scientific literature, experience of Matlab. Willingness to conduct wet-lab experiments would be essential.

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

This PhD will require the ESR to split their time between institutions located in Germany (Berlin, Würzburg) and the UK (Birmingham) and to be mobile across the network. As part of the ITN network, PhD students have an excellent opportunity to gain access to a wide variety of training activities, student workshops and international conference events organized by the network. The successful ESR9 candidate will also have a unique opportunity to gain crucial experience of a broad range of state-of-the-art technologies and systems biology and bioinformatics approaches in academia and industry.

Project details: Recent work has highlighted a crucial role for CLEC-2 in platelet activation and thrombosis, however, the underlying mechanisms of this control still remain elusive. This project aims to decipher these mechanisms, combining state-of-the art computational modelling, omics, imaging and systems biology approaches to explore the key molecular processes controlling CLEC-2 function and identify novel targets that impact on platelet regulation controlled by this receptor.

We employ a unique, large-scale computational model of a cellular signal transduction network that will be adapted throughout the project to investigate the functional effects of perturbations to the CLEC-2-associated signalling network (Berlin, Würzburg). 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 (Würzburg, Birmingham).

For further information please see the TAPAS website: https://more.bham.ac.uk/tapas/

Apply here: https://more.bham.ac.uk/tapas/vacancies/

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

Röhr, C et al. (2013) High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal, Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications. PLoS One 8(7): e67461. doi: 10.1371/journal.pone.0067461


Wierling, C et al. (2012) Prediction in the face of uncertainty: a Monte Carlo-based approach for systems biology of cancer treatment. Mutation Research; 746(2):163-70. doi: 10.1016/j.mrgentox.2012.01.005


Ogilvie, L.A., et al. (2015) 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. (2017) Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors. Nature Communications 8: doi: 10.1038/ncomms14262


Rayes, J. et al. (2017) The podoplanin-CLEC-2 axis inhibits inflammation in sepsis. Nature Communications 8:2239. doi: 10.1038/s41467-017-02402
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