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Prof David Beech
Dr L H Jiang
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Every cell is exposed to subtle but important physical events that arise, for example, from haemodynamic forces or local interactions as cells move and experience tissue expansion or retraction. A cell type that has striking ability to sense frictional force (shear stress) is the endothelial cell (Chiu & Chien 2011 Physiol Rev 91, 327-387). Determination of the mechanisms by which these and other cells sense shear stress remains one of the major unsolved questions of biology. We recently identified a membrane protein that is important in shear stress sensing. The project will investigate this protein and establish mechanistic understanding using a spectrum of cutting-edge imaging, electrophysiology and molecular/cell biology techniques.
Objectives of the project will be: To generate mutants of the membrane protein to determine domains for interaction within the sensor complex and for signaling to downstream pathways that include the P2X4 receptor; To identify and investigate associated pathways through proteomics. The project will build on our recent breakthrough to address one of the outstanding challenges of biological research - the mechanism of shear stress sensing. The mechanism is amenable to study and suitable for generation of data for high quality publication. A breadth of techniques will be used. The student will work in modern laboratory space with access to cutting-edge techniques. She/he will join a vibrant research group of 10-15 people which will give an opportunity for a broad and stimulating experience.
Objectives of the project will be: To generate mutants of the membrane protein to determine domains for interaction within the sensor complex and for signaling to downstream pathways that include the P2X4 receptor; To identify and investigate associated pathways through proteomics. The project will build on our recent breakthrough to address one of the outstanding challenges of biological research - the mechanism of shear stress sensing. The mechanism is amenable to study and suitable for generation of data for high quality publication. A breadth of techniques will be used. The student will work in modern laboratory space with access to cutting-edge techniques. She/he will join a vibrant research group of 10-15 people which will give an opportunity for a broad and stimulating experience.
Funding Notes
4 year BBSRC studentship, under the White Rose Mechanistic Biology DTP.
The successful applicant will receive fees and stipend (c.£13590 for 2013-14). The PhD will start in Oct 2013.Applicants should have, or be expecting to receive, a 2.1 Hons degree in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support.
There are 2 stages to the application process. Please see our website for more information:
http://www.fbs.leeds.ac.uk/gradschool/keywords/mnuFindaphd.php
The successful applicant will receive fees and stipend (c.£13590 for 2013-14). The PhD will start in Oct 2013.Applicants should have, or be expecting to receive, a 2.1 Hons degree in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support.
There are 2 stages to the application process. Please see our website for more information:
http://www.fbs.leeds.ac.uk/gradschool/keywords/mnuFindaphd.php
References
Chiu & Chien 2011 Physiol Rev 91, 327-387
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Career overview
Professor David J Beech completed undergraduate studies at the University of Manchester and obtained a PhD from St George’s Hospital Medical School in London. He further trained in biophysics at the University of Washington in Seattle before returning to the UK as a Wellcome Career Development Fellow. Currently, he serves as Professor of Cardiovascular Science at the University of Leeds and holds the position of Honorary Professor of Cardiovascular Science at the Leeds Teaching Hospitals NHS Trust (LTHT). He is also an elected Fellow of the Academy of Medical Sciences. Professor Beech leads a research group and is the NIHR BRC Cardiometabolic Disease Theme Lead. He is a co-founding partner of the Calcium-permeable channel Therapeutic Innovation Company (CalTIC), which operates across the UK and Germany. His research interests include the role of mechanical factors in cardiovascular structures and functions, particularly through force-sensing PIEZO1 calcium-permeable channels, and exploring new therapeutic approaches through the modulation of these channels and other calcium-permeable channels formed by TRPC1/4/5 proteins. Professor Beech is dedicated to team science and interdisciplinary collaborations, focusing on the potential benefits of his research for patients facing unsolved health issues such as heart failure and fetal growth restriction. He is also a co-investigator at the Tommy’s National Centre for Preterm Birth Research, contributing to studies on early life predispositions to adult cardiovascular disease.
Research interests
Professor Beech''s research focuses on the role of mechanical factors in determining cardiovascular structures and functions, particularly through force-sensing PIEZO1 calcium-permeable channels. He is interested in the molecular mechanisms of PIEZO1 channels and the potential for therapeutic interventions via small-molecule modulation of PIEZO1 and other calcium-permeable channels formed by TRPC1/4/5 proteins. His work aims to address significant health issues, including heart failure due to aortic stenosis and myocardial ischaemia, physical exercise intolerance in heart failure, fetal growth restriction, and small for size liver disease. He leads the Cardiometabolic Disease Theme at the National Institute for Health and Care Research (NIHR) Biomedical Research Centre and is a co-founding partner of the Calcium-permeable channel Therapeutic Innovation Company (CalTIC). Additionally, he is involved in mechanobiology studies at the Tommy’s National Centre for Preterm Birth Research, focusing on early life predispositions to adult cardiovascular disease.
Cardiovascular Science
Calcium-Permeable Channels
Mechanical Force Sensing
Health
Disease
PIEZO1 Channels
TRPC1/4/5 Proteins
Therapeutic Approaches
Heart Failure
Aortic Stenosis
Myocardial Ischemia
Physical Exercise Intolerance
Fetal Growth Restriction
Small for Size Liver Disease
Team Science
Collaborations
Mechanobiology
Cardiometabolic Disease
Biomedical Research Centre
Calcium-Permeable Channel Therapeutic Innovation Company
Preterm Birth Research.
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