Exploring the therapeutic potential of calmodulin in the context of inherited cardiac arrhythmia

We are looking for a highly motivated student to work with us on an exciting 3-year British Heart Foundation (BHF)-funded project to explore the therapeutic potential of calmodulin in the context of inherited cardiac arrhythmia.

Long QT Syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are congenital cardiac disorders that can affect children. Symptoms include fainting, seizures and can lead to life-threatening arrhythmia. Human genetic mutations in the ubiquitous calcium sensor calmodulin (CaM) have been identified in patients living with LQTS and CPVT, suggesting a key role of CaM in the molecular aetiology of the diseases. Current management often involving beta-blockers or implantable devices present significant limitations and side effects. Beta-blockers can cause fatigue, dizziness and not all patients respond optimally. Implantable devices carry a significant risk of infection and device-related complications. Therefore, there is an imperative need to explore alternative therapeutic strategies. In CaM-associated LQTS and CPVT syndromes, CaM’s ability to sense calcium, and interact with and regulate ion channels relevant to cardiac muscle contraction is impaired.

In this project, we will develop, characterise and validate hypersensitive CaM variants (CaM HS) with improved calcium binding properties and the ability to restore ion channel regulation, as a novel therapeutic avenue. With recent promising advances in protein replacement therapy, our findings will reveal the therapeutic potential of CaM in the context of inherited cardiac arrhythmia.

This is an exceptional opportunity for the successful applicant to receive comprehensive research training in techniques ranging from molecular cloning, protein biochemistry, structural biology and electrophysiology. The successful applicant will gain experience in dissemination of scientific knowledge by preparing articles for publication and through presenting findings at both national and international research conferences. Broader research training will also be provided through the University’s PGR training programme and doctoral training college.

The student will be supervised by Dr Nordine Helassa and Prof Caroline Dart who will provide training and support in all relevant techniques. The project will be hosted in the Department of Biochemistry, Cell and Systems Biology in the Institute of Systems, Molecular and Integrative Biology (ISMIB).

https://www.liverpool.ac.uk/systems-molecular-and-integrative-biology/

We are looking for a highly motivated student who is willing to pursue cutting-edge research within a vibrant and collegiate team. A basic background in protein biochemistry would be beneficial. The ISMIB is fully committed to promoting and supporting equality, diversity and inclusion. In recruitment, we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Essential eligibility requirements:

• BSc (minimum 2.1 honours degree) in Biochemistry or a related discipline.

• Excellent communication skills.

Enquiries to: Dr Nordine Helassa (nhelassa@liverpool.ac.uk)

To apply: Applicants should send a CV, covering letter (2-page max), and the names of at least two references to Dr Nordine Helassa, nhelassa@liverpool.ac.uk