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Investigating the regulatory pathways for intracellular sodium in the atria

  • Full or part time

    Dr S Thomas
  • Application Deadline
    Sunday, April 14, 2019
  • Funded PhD Project (UK Students Only)
    Funded PhD Project (UK Students Only)

Project Description

Research interests/description of main research theme:

Applications are invited for a 3-year fully-funded British Heart Foundation PhD Studentship starting in October 2019, under the guidance of Dr Davor Pavlovic and Dr Steve Thomas. The purpose of this Studentship is to uncover how sodium is handled in atrial chambers of the heart and to investigate the consequences of intracellular sodium changes in the atria in health and disease.

Project summary: Intracellular sodium concentration is increasingly recognised as an important modulator of physiological function in the heart. Whereas, the processes driving regulation of sodium in health and disease are well studied in the ventricles, little of such data is available for the atria. In this project we will employ our expertise in atrial cardiomyocyte physiology, in combination with sodium-fluorescent dyes and state-of-the-art optical mapping in order to investigate intracellular sodium regulatory mechanisms and responses to clinically relevant antiarrhythmics in isolated atrial myocytes and whole atria. Furthermore, we propose to employ state of the art super-resolution imaging techniques to investigate expression and localisation of key proteins contributing to regulation of intracellular sodium in isolated atrial cardiomyocytes. Insights from these studies will contribute to better understanding of the atrial specific intracellular sodium regulatory pathways. Considering that atrial sodium channels and sodium pumps are primary targets of antiarrhythmic medications, our findings will advance understanding of treatment for patients with supraventricular rhythm disorders.

Research Environment and Learning Outcomes: Dr Pavlovic and Dr Thomas have published extensively on intracellular sodium regulation in the heart, assessment of electrical function and super-resolution imaging (1-5). A range of molecular biology, electrophysiology, optical mapping, single-cell fluorescence imaging and super-resolution imaging techniques will be used during this studentship and all the necessary equipment is already available at the department. The student will also benefit further from being integrated within the Translational Research on Heart Failure and Arrhythmias Cluster, and thereby access to clinical expertise within it, as well as the Centre of Membrane Proteins and Receptors (COMPARE) within the University of Birmingham. This studentship offers an opportunity to study in an excellent research environment and in an institute with world class facilities and resources devoted to understanding the mechanisms of cardiovascular disease and driving new translational therapies for patients.

Person Specification
Applicants should ideally have a commitment to cardiovascular research and preferably demonstrate experience in cellular and organ level cardiovascular methods, electrophysiology, microscopy and molecular biology techniques (desired, not required). Applicants should also hold or be willing to acquire an animal handling home office licence and work as part of a multidisciplinary research team. Applicant should hold or realistically expect to obtain at least an Upper-Second Class Honours Degree in Pharmacological, Biological or Biomedical Sciences.

For more information about Dr Davor Pavlovic, Dr Steve Thomas, the Institute of Cardiovascular Sciences, and the COMPARE please see :
http://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/pavlovic-davor.aspx
https://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/Thomas-Steve.aspx
http://www.birmingham.ac.uk/research/activity/cardiovascular-sciences/index.aspx
https://www.birmingham.ac.uk/research/activity/cardiovascular-sciences/research/heart-failure-arrhythmias/index.aspx
http://www.birmingham-nottingham.ac.uk/compare/

Funding Notes

British and EU nationality applicants are eligible for both the cost of tuition fees and a yearly stipend (starting at £19,919 per annum and increasing annually) over the course of the PhD programme.

How to apply


Applications should be directed to David Piela []

To apply, please send:

• A Detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities and relevance to this application;
• Copies of your degree transcripts;
• Evidence of your proficiency in the English language, if applicable

References

1. Pavlovic D, Fuller W and Shattock MJ (2013) Novel regulation of cardiac Na pump via phospholemman. Journal of Molecular and Cellular Cardiology Aug; 61:83-93

2. Ackers-Johnson M, Li PY, Holmes AP, O'Brien SM, Pavlovic D and Foo RS. (2016) A Simplified, Langendorff-Free Method for
Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart. Circ Res. 2016 Aug 119(8):909-20

3. Syeda F, Holmes AP, Yu YT, Tull S, Kuhlmann SM, O'Brien S, Pavlovic D, Betney D, Kucera JP, Rohr S, Brown NA, Fabritz L, Kirchhof P (2016) PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers. JACC 68(17):1881-1894.

4. O'Shea C, Holmes AP, Yu TY, Winter J, Wells SP, Correia J, Boukens BJ, De Groot JR, Chu GS, Li X, Ng GA, Kirchhof P, Fabritz L, Rajpoot K, Pavlovic D (2019) ElectroMap: High-throughput open-source software for analysis and mapping of cardiac electrophysiology. Sci Rep. Feb 4;9(1):1389.

5. Poulter NS, Pollitt AY, Davies A, Malinova D, Nash GB, Hannon MJ, Pikramenou Z, Rappoport JZ, Hartwig JH, Owen DM, Thrasher AJ, Watson SP, Thomas SG. (2015) Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex. Nat Commun. Jun 1;6:7254

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