or
Continue with FacebookLooking to list your PhD opportunities? Log in here.
This project is no longer listed on FindAPhD.com and may not be available.
Click here to search FindAPhD.com for PhD studentship opportunities
Dr A.J. Smith
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
This project will build on our recent exciting discovery that a novel chemical tool, the polymer styrene maleic acid (SMA), can ‘biopsy’ human vascular cells, extracting proteins from the membrane without killing the cells. This polymer inserts into lipid bilayers transiently before leaving as a ‘nanodisc’ containing a sample of the membrane (lipid and protein), maintaining structure and protein post-translational modifications. We have shown for the first time that this technique can obtain proteins without losing cell viability.
This project will explore SMA as a way to biopsy cells of the vasculature to obtain proteins and other biomarkers that inform disease diagnosis and/or management. Our targets will be the early markers of clinical atheroma in endothelial and smooth muscle cells, characterising the application in the identification of specific, key markers of a critically-important disease. This will be achieved using cells in culture, then extended to intact human vascular tissue. The techniques involved will include assays of cell viability and functional analyses, with protein characterisation by mass spectrometry and Western blotting. There is the possibility of further collaborative work to carry out analysis of model cells, to precisely establish the limits of detection for this novel cell biopsy technique.
This project will explore SMA as a way to biopsy cells of the vasculature to obtain proteins and other biomarkers that inform disease diagnosis and/or management. Our targets will be the early markers of clinical atheroma in endothelial and smooth muscle cells, characterising the application in the identification of specific, key markers of a critically-important disease. This will be achieved using cells in culture, then extended to intact human vascular tissue. The techniques involved will include assays of cell viability and functional analyses, with protein characterisation by mass spectrometry and Western blotting. There is the possibility of further collaborative work to carry out analysis of model cells, to precisely establish the limits of detection for this novel cell biopsy technique.
Funding Notes
The PhD will start when a suitable applicant is selected and funding confirmed. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) or above in a relevant subject. The funding is open to international students (subject to eligibility); self-funded students, or those with funding already available and seeking a suitable research project, are encouraged to apply. For further details, please contact Dr. Smith ([Email Address Removed]).
References
Lee SC, Knowles TJ, Postis VL, Jamshad M, Parslow RA, Lin YP, Goldman A, Sridhar P, Overduin M, Muench SP, Dafforn TR. A method for detergent-free isolation of membrane proteins in their local lipid environment. Nature Protocols 2016; 11(7):1149-62.
How good is research at University of Leeds in Biological Sciences?
Research output data provided by the Research Excellence Framework (REF)
Click here to see the results for all UK universitiesProject supervisors
Career overview
Dr Andrew Smith completed a medical degree (MBChB) at the University of Aberdeen in 2001 and subsequently worked clinically for several years. He pursued a research PhD in Neuroscience and Biomedical Systems at the University of Glasgow, which he completed in 2008. Following his doctoral studies, Dr Smith worked as a post-doctoral researcher at Liverpool John Moores University from 2009 to 2013, and then at King''s College London from 2013 to 2015. He is currently a Lecturer in Cardiovascular Science at the University of Leeds, where he also leads the MBiol Programme in the School of Biomedical Sciences and serves as the Admissions Tutor for the school.
Research interests
Dr. Smith''s research focuses on cardiac regeneration, cardiovascular stem and progenitor cells, and cardiotoxicity. A primary interest is in the role of endogenous cardiac progenitor cells (CPCs) in myocardial tissue maintenance and repair. His group investigates how these cells contribute to normal myocardial function and respond to injury, demonstrating their potential to differentiate into various cell types and repair myocardial tissue. Dr. Smith''s previous work has highlighted the critical role of CPCs in myocardial tissue maintenance following diffuse cardiac injury and the potential for growth factors to enhance their activity and improve recovery after myocardial infarction. Additionally, Dr. Smith is currently examining the effects of receptor tyrosine kinase inhibitors (RTKIs), which are known cardiotoxins, on CPCs. His research explores how these anti-cancer drugs impact CPC phenotype, self-renewal, differentiation, and the pro-survival secretome, as well as their overall effects on heart function. This work aims to identify new treatment avenues for RTKI-induced cardiotoxicity and to leverage CPCs'' regenerative potential for heart failure treatment. Another significant area of Dr. Smith''s research involves understanding cell death mechanisms in CPCs induced by RTKIs, focusing on the pathways involved and associated changes in intracellular calcium and reactive oxygen species levels. This study employs various techniques, including cell culture and confocal analysis, to elucidate the toxic effects of RTKIs on cardiac cells. Dr. Smith''s group is also developing a novel method for non-destructive cell protein ''biopsy'' using amphipathic polymers, which allows for the extraction of proteins from cells without causing cell death. This method has been successfully applied to human cardiovascular cells and aims to identify biomarkers for early vascular complications of diabetes mellitus. Overall, Dr. Smith''s research encompasses a broad range of topics within cardiovascular science, with a strong emphasis on the biology of cardiac progenitor cells and their potential therapeutic applications.
Cardiac Regeneration
Cardiovascular Stem Cells
Progenitor Cells
Cardiotoxicity
Cell Culture
Myocardial Tissue Maintenance
Endogenous Cardiac Progenitor Cells
High-Intensity Exercise
Receptor Tyrosine Kinase Inhibitors
Cell Death Mechanisms
Non-Destructive Cell Biopsy
Amphipathic Polymers
Protein Expression
Biomarkers
Heart Failure
Regenerative Potential
Cardiovascular Science
Admissions Tutor
Medical Degree
PhD in Neuroscience
Post-Doctoral Research
Research Interests
Cardiovascular Tissue
Myocardial Function
Tissue Repair
Growth Factors
Functional Recovery
Cell Signalling Mechanisms
Clinical Research
Collaborative Studies.
Find a scholarship to fund your dream Masters
Sign in to view and filter all scholarship opportunities
or
Continue with Facebook