University of Reading Featured PhD Programmes
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University College London Featured PhD Programmes

Using CRISPR in iPS cells to modify platelet function


   School of Biological Sciences


Reading United Kingdom Biochemistry Bioinformatics Cell Biology Health Informatics Molecular Biology Medicine Pharmacology

About the Project

Platelets are the small cells in the blood whose job it is to prevent bleeding. Under normal conditions, when they encounter a damaged blood vessel they become activated and form a thrombus. In cardiovascular disease platelets can form unwanted thrombi which block blood vessels, or break away (embolise) causing blockages elsewhere. This can cause a heart attack or stroke.

Understanding how platelets become activated is key to developing new drugs to prevent these life-threatening conditions. However, as platelets lack a nucleus, research into platelet proteins can only go so far without the use of mouse models. This project will use a different approach, instead using iPS cells to generate human platelets (from their pre-cursor cell, the megakaryocyte) in vitro. CRISPR gene editing technology will be used to modify platelet proteins to study their function, without the need to generate mutant mouse lines.

Based in the Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, which provides a multidisciplinary interactive research environment for over 30 research groups, this project will provide an excellent opportunity for training in a wide range of basic molecular and cell biology methods including flow cytometry, immunoprecipitation, as well as specialist training in microscopy techniques such as confocal.

School of Biological Sciences, University of Reading:

The University of Reading, located west of London, England, provides world-class research education programs. The University’s main Whiteknights Campus is set in 130 hectares of beautiful parkland, a 30-minute train ride to central London and 40 minutes from London Heathrow airport.

Our School of Biological Sciences conducts high-impact research, tackling current global challenges faced by society and the planet. Our research ranges from understanding and improving human health and combating disease, through to understanding evolutionary processes and uncovering new ways to protect the natural world. In 2020, we moved into a stunning new ~£60 million Health & Life Sciencesbuilding. This state-of-the-art facility is purpose-built for science research and teaching. It houses the Cole Museum of Zoology, a café and social spaces.

In the School of Biological Sciences, you will be joining a vibrant community of ~180 PhD students representing ~40 nationalities. Our students publish in high-impact journals, present at international conferences, and organise a range of exciting outreach and public engagement activities.

During your PhD at the University of Reading, you will expand your research knowledge and skills, receiving supervision in one-to-one and small group sessions. You will have access to cutting-edge technology and learn the latest research techniques. We also provide dedicated training in important transferable skills that will support your career aspirations. If English is not your first language, the University's excellent International Study and Language Institute will help you develop your academic English skills.

The University of Reading is a welcoming community for people of all faiths and cultures. We are committed to a healthy work-life balance and will work to ensure that you are supported personally and academically.

Eligibility:

Applicants should have a good degree (minimum of a UK Upper Second (2:1) undergraduate degree or equivalent) in Biomedical Sciences or a strongly-related discipline. Applicants will also need to meet the University’s English Language requirements. We offer pre-sessional courses that can help with meeting these requirements.

How to apply:

Submit an application for a PhD in Biomedical Sciences at http://www.reading.ac.uk/pgapply.

Further information: http://www.reading.ac.uk/biologicalsciences/SchoolofBiologicalSciences/PhD/sbs-phd.aspx

Enquiries: Dr Craig Hughes ()


References

"Moreau T, Evans AL, Vasquez L, Tijssen MR, Yan Y, Trotter MW, Howard D, Colzani M, Arumugam M, Wu WH, Dalby A, Lampela R, Bouet G, Hobbs CM, Pask DC, Payne H, Ponomaryov T, Brill A, Soranzo N, Ouwehand WH, Pedersen RA, Ghevaert C. (2016) Large-scale production of megakaryocytes
from human pluripotent stem cells by chemically defined forward programming. Nat Commun. 2016 Apr 7;7:11208. doi: 10.1038/ncomms11208
Pollitt, A. Y., Hughes, C. E. and Watson, S. P. (2013) GPVI and CLEC-2. In: Michelson, A. D. (ed.) Platelets. 3rd edition. Academic Press, Amsterdam, pp. 215-231. ISBN 9780123878373 doi: https://doi.org/10.1016/B978-0-12-387837-3.00011-0
Nicolson, P. L. R., Hughes, C. E., Watson, S., Nock, S. H., Hardy, A. T., Watson, C. N., Montague, S. J., Malcor, J.-D., Thomas, M. R., Pollitt, A. Y., Tomlinson, M. G., Pratt, G. and Watson, S. P. (2018) Inhibition of Btk by Btk-specific concentrations of ibrutinib and acalabrutinib delays but does not block platelet aggregation to GPVI. Haematologica, 103 (9). ISSN 1592-8721 doi: https://doi.org/10.3324/haematol.2018.193391

Please also view Dr Craig Hughes' academic profile:
http://www.reading.ac.uk/biologicalsciences/SchoolofBiologicalSciences/Meetourteam/staff/c-e-hughes.aspx

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