Background to research and synopsis
Cardiovascular disease (CVD) is the world’s single biggest killer causing 1 in 3 deaths. Drug-induced cardiac damage (e.g. arrhythmias, cardiac hypertrophy, and heart failure) is also a major global issue in drug treatment of chronic disorders (e.g. cancer, CVD, diabetes, depression) and limits drug efficacy and development.
STARS KD in cardiomyocytes renders cells susceptible to oxidative stress-induced cell death . Over-expression of STARS in cardiomyocytes led to hypertrophy . STARS is epigenetically regulated and controlled by the pivotal cardiac factor GATA4 . Therefore STARS is a novel and essential nodal point in cardiac cell survival and remodelling and an attractive therapeutic target. However, the mechanism of STARS action and how it is precisely regulated is still unclear.
In this project, the scholar will use established state-of-the-art in vitro and in vivo approaches (e.g. human iPSC-CM, SiRNA/CRISPR, Seahorse Analyzer), coupled with cardiac disease model systems (cellular hypertrophy, apoptosis, mitochondrial dysfunction, intact Drosophila heart prep, ex-vivo heart prep), to elucidate the mechanisms of STARS in cardioprotection. This is a multidisciplinary project utilising the strengths at the University of Westminster and two other renowned UK Institutions. They will acquire knowledge in high-profile areas of research (heart disease, cardiotoxicity, metabolism, gen regulation) and cutting-edge techniques. The scholar will be encouraged to present their findings in renowned international conferences (AHA, ESC).
Recent publications by supervisors that are relevant to the project
Nino Porakishvili, Uzma Sayed, Emanuela Volpi, Kristina Zaitseva, Edward A.Clark, Kanti R.Rai, Amit Nathwani, Nicholas Chiorazziand Peter M.Lydyard. Synergistic pro-apoptotic signalling pathways mediated through CD180 toll-like receptor and sIgD in Chronic Lymphocytic Leukaemia (CLL) cells. Paper in preparation.
Porakishvili Nino, Vispute Ketki, Rajakaruna Nadeeka, Andrew Steele, Kulikova Nina, Clark Edward A., Rai Kanti R., Nathwani Amit, Damle Rajendra N., Chiorazzi Nicholas and Lydyard, Peter M. Rewiring of sIgM-mediated intracellular signaling through theCD180 Toll-like receptor. Molecular Medicine, 2015, 21: 46-57.
Porakishvili Nino, MemonAzka, VisputeKetki, Kulikova Nina, Clark Edward A., Rai Kanti R., NathwaniAmit, DamleRajendra N., ChiorazziNicholas and Lydyard, Peter M. CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells. Br J Haematol, 2011, 153:486–498.
JA Walton, PM Lydyard, A Nathwani,VEmery, A Akbar, MJ Glennie and N Porakishvili. Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4+ perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype. Br J Haematol. 2010, 148, 274-84.
We have identified a cardiac-enriched gene named STARS that plays a pivotal role in heart function. STARS knockdown (KD) in zebrafish resulted in dilated cardiomyopathy, decreased ventricular function and arrhythmia, which was reversed by co-injection of SRF mRNA . Cardiac-specific STARS KD in Drosophila rendered the heart arrhythmic .
Our group have recently identified a novel cardioprotective signalling pathway that impinges on diverse disease-related gene networks involving STARS. We have identified an endogenous mediator that modulates several key cardioprotective genes during stress including STARS.
A Warford and E Volpi. In situ Hybridization: Key Concepts and Applications, 2017. In: Orchard G. and Nation B. (eds), “Histopathology” (2nd Edition), Fundamentals of Biomedical Sciences, Oxford University Press.
M Usman and EVolpi. DNA damage in obesity: initiator, promoter and predictor of cancer. Reviews in Mutation Research, 2018, 778: 23-37.
R Real, M Peter, A Trabalza, S Khan, MA Smith, J Dopp, SJ Barnes, A Momoh, A Strano, E Volpi, G Knott, FJ Livesey and V De Paola, 2018. In vivo modeling of human neuron dynamics and Down syndrome. Science, 2018, 362:
A Warford and E. Volpi, 2019. Intact sample analysis. In: Warford A. and Presnaeu N. (eds), “Molecular Diagnostics”, Fundamentals of Biomedical Sciences, Oxford University Press.
Candidates should normally have a minimum classification of 2.1 in their Bachelor Degree or equivalent and preferably a Masters degree. Applicants whose secondary level education has not been conducted in the medium of English should also demonstrate evidence of appropriate English language proficiency normally defined as IELTS: 6.5 (overall score with not less than 6.0 in any of the individual elements).
Please follow this link to apply for the programme most appropriate to your research, please note that the programme appears as MPhil on UCAS, however there is an option on the form to request PhD via MPhil, which is the standard route:
To make your application for (SLS11):
Interviews will be held in June/July 2019. The Studentship title is SLS11 Full Scholarship and Fee Waiver School of Life Sciences. Please include this in your application, you must also list the Project Code in order for us to allocate your application to the correct.