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Causes of stress induced cardiac arrhythmia

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  • Full or part time
    Dr J Winter
    Dr D Pavlovic
  • Application Deadline
    Applications accepted all year round

About This PhD Project

Project Description

Abnormal heart rhythms, known as arrhythmia, are a major cause of morbidity and mortality, particularly in individuals with pre-existing cardiovascular disease. Atrial fibrillation, the most common cardiac arrhythmia, affects some 2% of the general population and is a major cause of stroke. Meanwhile, cardiac arrhythmia of the ventricles (lower chambers of the heart), which are usually associated with ischaemic heart disease and/or heart failure, can result in death within minutes in the absence of medical intervention. It is thought that abnormalities in the electrical and calcium handling properties of the heart, secondary to progressive molecular and structural remodelling due to chronic stress, are an important driver of cardiac arrhythmia. In isolated cardiac myocytes, there is a well-established relationship between progressive heart disease and susceptibility to spontaneous contractions (ectopic beats); events driven by the spontaneous release of calcium ions from intracellular store.1 However, it is not well understood how these events causes arrhythmia in the intact heart; where electrical coupling between neighbouring is predicted to suppress ectopic beats.2,3
Applications are invited for a 3-year self-funded PhD Studentship in the laboratory of James Winter, PhD, which aims to address the tissue-level determinants of premature beats in the heart and their role in cardiac arrhythmia. The appointed student will utilise fluorescent and electrogram-based recording techniques to investigate the impact of a range of acute and chronic interventions on the behaviour of ectopic activity in intact tissues (isolated atria, cardiac slices, and isolated hearts).4 Studies will focus on how dysfunction in intracellular calcium-handling processes and cell-to-cell coupling influence ectopic activity in atrial and ventricular tissues; with direct relevance to cardiac disease. Studies will utilise isolated tissues from normal animals and those with surgically-induced cardiac hypertrophy and heart failure; mimicking two clinically relevant heart conditions.
All equipment to deliver the research proposal is available within Dr Winter’s laboratory and the appointee will be trained in a range of techniques, including, micro-surgery, fluorescent microscopy, basic molecular biology, and data analysis, which will include training in the MatLab programming language. Opportunities will be provided for the appointee to present their research findings at national and international scientific meetings.
Person Specification
Applicants should have a strong background in biomedical science, preferably in mammalian physiology. They should have a commitment to cardiovascular research and hold, or realistically expect to obtain, at least an Upper Second-Class Honors Degree in a relevant subject.
For more information about the Winter and Pavlovic research groups and the Institute of Cardiovascular Sciences at the University of Birmingham see…
https://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/winter-james.aspx
http://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/pavlovic-davor.aspx
http://www.birmingham.ac.uk/research/activity/cardiovascular-sciences/index.aspx
To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in each Institute, the funding opportunities for each subject, and guidance on making your application, you can now order your copy of the new Doctoral Research Prospectus, at:
www.birmingham.ac.uk/students/drp.aspx
How to apply
Informal enquiries should be directed to Dr James Winter ([Email Address Removed]).
To be considered for this studentship, please send the following documents to Dr James Winter ([Email Address Removed]).
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.

References

References:
1) https://www.tandfonline.com/doi/abs/10.1080/713609356 - review article on basic mechanisms of calcium-mediated cardiac arrhythmia
2) http://circres.ahajournals.org/content/84/12/1459 - study on the propagation of calcium waves in intact cardiac tissue at room temperature.
3) https://www.sciencedirect.com/science/article/pii/S000634951730293X - combined modelling and experimental paper focused on the mechanisms determining delayed afterdepolarisations at subcellular through to multicellular levels. Note that tissue-level effects are computational simulations.
4) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787134/ - recent publication from Dr Winter and Dr Pavlovic, highlighting some of the techniques to be used in the studentship (optical mapping, isolated heart perfusion).



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