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Investigating the role of calmodulin in human muscular hypotonia and immunodeficiency


   Institute of Life Course and Medical Sciences

  , , Prof Alexei Tepikin  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Recently, human gene mutations in the calcium channels Orai1 and STIM1 have been identified in patients with immunodeficiency and muscular hypotonia syndromes. As these mutations are located in calmodulin-binding regions, we hypothesise that calmodulin play an important role in the molecular mechanism of these diseases. However, calmodulin regulation in the context of “channelopathies” has not been investigated yet and remains unknown.

In this project, we will use a multidisciplinary approach to determine the role of calmodulin in the molecular mechanism of human muscular hypotonia and immunodeficiency. Data obtained from this project will open opportunities for developing new therapeutic avenues of investigation.

This is an exceptional opportunity for the successful applicant to receive comprehensive research training in techniques ranging from molecular cloning, protein biochemistry, structural biology, electrophysiology, cell biology and fluorescence microscopy.

The student will be supervised by Dr Nordine Helassa, BHF Research Fellow in Cardiovascular Science, Prof Caroline Dart and Prof Alexei Tepikin who will provide training and support in all relevant techniques. The project will be hosted in the Department of Cardiovascular and Metabolic Medicine in ILCaMS.

https://www.liverpool.ac.uk/life-course-and-medical-sciences/

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 ILCaMS 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 a related discipline.

• Excellent communication skills.

Enquiries to: Dr Nordine Helassa ()

To apply: Applicants should send a CV and a covering letter (2-page max) to Dr Nordine Helassa,

Expected interview date/week: Suitable candidates will be contacted for an interview shortly after applying


Funding Notes

The successful applicant will be expected to provide the funding for tuition fees, living expenses as well as contributing to research costs.

References

1. Lacruz RS, Feske S. Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci. 2015 Nov;1356(1):45-79. doi: 10.1111/nyas.12938. Epub 2015 Oct 15. PMID: 26469693; PMCID: PMC4692058.
2. Li X, Wu G, Yang Y, Fu S, Liu X, Kang H, Yang X, Su XC, Shen Y. Calmodulin dissociates the STIM1-Orai1 complex and STIM1 oligomers. Nat Commun. 2017 Oct 19;8(1):1042. doi: 10.1038/s41467-017-01135-w. PMID: 29051492; PMCID: PMC5648805.
3. Mullins FM, Park CY, Dolmetsch RE, Lewis RS. STIM1 and calmodulin interact with Orai1 to induce Ca2+-dependent inactivation of CRAC channels. Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15495-500. doi: 10.1073/pnas.0906781106. Epub 2009 Aug 21. PMID: 19706428; PMCID: PMC2741279.

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