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Dr Munir Hussain,
Dr Talat Nasim,
Prof Mark Boyett
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
APC is an anticoagulant enzyme that also exerts antithrombotic, anti-inflammatory, antiapoptotic and a variety of other cytoprotective effects in different tissues, where the mechanism of action is thought to involve the endothelial protein C receptor (EPCR) and a protease activated receptor (PAR). Although the presence of PARs in cardiac muscle has been known for some years, their functional relevance has never been established. Preliminary data supporting this project show that APC has direct, endothelium-independent, effects on intracellular calcium concentration, L-type Ca2+ current and inward rectifying K+ currents in isolated cardiomyocytes, which may or may not be dependent on PARs. The focus of this project is therefore to fully characterise these effects of APC on cardiac myocytes and to determine the receptor and signal transduction mechanisms that mediate these effects.
Two complementary series of experiments will be performed using adult rat ventricular myocytes: First, physiological measurements of [Ca2+]i and membrane currents will establish the full extent of the effects of APC in the heart and associated peptide derivatives. This will be done using the methodology (collagenase isolation of cardiac myocytes, Ca2+ imaging and voltage/current clamp) already established in the Dr Hussain’s laboratory. Secondly, biochemical experiments will investigate the receptor type/subtype and the associated signalling mechanisms mediating the physiological response to APC and the related peptides. A particular focus of these experiments will be to determine the involvement of cyclic AMP-Protein kinase A, AMP kinase and MAP kinases in the responses to APC and the related peptide derivatives of APC.
This project will lead to the generation of new and novel data on the signal transduction mechanisms that mediate the effects of APC and may lead to the development of novel tissue-selective therapies to treat cardiovascular disease.
The PhD student will work in well equipped laboratories and be supervised by an experienced team of scientists. The methodologies to be used are in demand in academia and industry, and will therefore provide training for a successful career opportunities in the future.
How to apply
Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account and select 'Full-time PhD in Biomedical Science' as the course, and then specify the project title when prompted.
About the University of Bradford
Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities.
Faculty of Life Sciences
The faculty comprises a mixture of academic divisions, research centres and outreach facilities. We provide high-quality teaching with a professional focus and engage in cutting-edge research – which we seek to apply through our extensive links with industry and business. We also offer a wide range of postgraduate taught and research courses.
Many of our academics are active researchers and international research experts.
Our interdisciplinary research themes are focus on:
- Computational and Data-driven Science
- Interface of Chemistry Biology and Materials
- Health, Society, People and Place
- The Life Course
Our research centres include:
- Centre for Pharmaceutical Engineering Science
- Digital Health Enterprise Zone
- Institute of Cancer Therapeutics
- Wolfson Centre for Applied Research
University investment in research support services, equipment and infrastructure provides an excellent research environment and broad portfolio of developmental opportunities.
Positive Action Statement
At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students.
Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.
These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies.
Funding Notes
This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee of £10,000 per year applies, in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support.
References
1. Griffin JH, Zlokovic BV, Mosnier LO (2015). Activated protein C: biased for translation. Blood 125(19):28988-2907. https://doi.org/10.1182/blood-2015-02-355974
2. Salem, K.A., Qureshi, A., Ljubisavijevic, M., Hussain, M. and Howarth, F.C. (2009). Alloxan reduces amplitude of ventricular myocyte shortening and intracellular Ca2+ without altering L-type Ca2+ current, sarcoplasmic reticulum Ca2+ content or myofilament sensitivity to Ca2+. Mol. Cell. Biochem. 340(1-2):115-23. DOI 10.1007/s11010-010-0408-7
3. Wilson, C , Zi M, Smith M, Hussain M, D'Souza D, Dobrzynski H, Boyett MR (2023). Atrioventricular node dysfunction in pressure overload-induced heart failure-Involvement of the immune system and transcriptomic remodelling. Front Pharmacol 4;14: https://doi.org/10.3389/fphar.2023.1083910
4. Gillian A. Durham,GA, Williams, J, Nasim, MT, and Palmer, TM (2019). Targeting SOCS Proteins to Control JAK-STAT Signalling in Disease Trends in Pharm. Sci.,40(5): https://doi.org/10.1016/j.tips.2019.03.001
5. Nasim MT and Trembath, RC (2005). A dual-light reporter system to determine protein-protein interaction into mammalian cells. Nucleic Acids Res. 33(7): e66 (8 pages) https://doi.org/10.1093/nar/gni066.
2. Salem, K.A., Qureshi, A., Ljubisavijevic, M., Hussain, M. and Howarth, F.C. (2009). Alloxan reduces amplitude of ventricular myocyte shortening and intracellular Ca2+ without altering L-type Ca2+ current, sarcoplasmic reticulum Ca2+ content or myofilament sensitivity to Ca2+. Mol. Cell. Biochem. 340(1-2):115-23. DOI 10.1007/s11010-010-0408-7
3. Wilson, C , Zi M, Smith M, Hussain M, D'Souza D, Dobrzynski H, Boyett MR (2023). Atrioventricular node dysfunction in pressure overload-induced heart failure-Involvement of the immune system and transcriptomic remodelling. Front Pharmacol 4;14: https://doi.org/10.3389/fphar.2023.1083910
4. Gillian A. Durham,GA, Williams, J, Nasim, MT, and Palmer, TM (2019). Targeting SOCS Proteins to Control JAK-STAT Signalling in Disease Trends in Pharm. Sci.,40(5): https://doi.org/10.1016/j.tips.2019.03.001
5. Nasim MT and Trembath, RC (2005). A dual-light reporter system to determine protein-protein interaction into mammalian cells. Nucleic Acids Res. 33(7): e66 (8 pages) https://doi.org/10.1093/nar/gni066.
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