Developing a Drosophila melanogaster model of the cardiac myocyte action potential to investigate function and performance

Insects possess a rhythmically active tubular heart that shows remarkable similarity to the mammalian heart despite differing in gross structure. Studies in the fruit fly, Drosophila melanogaster, have demonstrated remarkable molecular and developmental similarities between the two. Key genes in heart development are homologous between insects and mammals (e.g. tinman), as are key components of cardiac myocyte physiology, including ion channels, pumps and exchangers.

Consequently, studies of the Drosophila heart can provide invaluable insights into the functioning of the mammalian hearts but little of this potential has been realised. Investigations of the Drosophila heart have focussed almost exclusively on the output of the larval heart measured through the electrocardiogram (ECG), ignoring the cellular level. Yet, heart cells are capable of showing substantial plasticity and redundancy so knowing the overall output is insufficient to characterise the impact of changes in molecular networks that are the targets of drugs. Thus, to realise the potential of the Drosophila heart for genetic screens and drug discovery it is essential to characterise all levels from molecular and cellular to organ/system.

The aim of the studentship is to characterise and produce a model of the cardiac myocyte action potential to study the electrical properties of the heart through applying existing techniques (e.g. sharp intracellular recordings, computational modelling) as well as the development of new techniques (e.g. whole-cell patch). With a model of the Drosophila heart based on a detailed electrical and mechanical characterisation it would be possible use large-scale genetic screens to make crucial insights into heart function and the possible impact of candidate drugs replacing the need for vertebrates. These insights can be used to inform subsequent vertebrate research leading to a reduction in the number of animals used in such studies.

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PhD Studentship

Status:

Active

Principal investigator

Dr Jeremy Niven

Institution

University of Sussex

Grant reference number

NC/N00261X/1

Award date:

Oct 2016 - Sep 2019

Grant amount

£90,000 (Joint award with BHF)