Investigating the role of calmodulin in human muscular hypotonia and immunodeficiency

Description

Project background and aims

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.

Student Experience

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) and Dr Caroline Dart (Professor in Physiology) 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.

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

Applicant information

We are looking for a highly motivated student who is willing to pursue cutting-edge research within a vibrant and collegiate team. The successful applicant should have an interest in basic biomedical research and hold a minimum undergraduate qualification 2:1, or equivalent, in a life science or health-related subject.

Research project related enquiries should be made in the first instance to Dr Nordine Helassa (nhelassa@liverpool.ac.uk).

To apply please send your CV to Dr Nordine Helassa (nhelassa@liverpool.ac.uk).

Availability

Open to students worldwide

Funding information

Self-funded project

We are looking for a self-funded student who has secured funding from an independent body. There is no financial support available from Liverpool for this study.

The successful applicant will be expected to have funding in place for the tuition fees (https://www.liverpool.ac.uk/study/postgraduate-research/fees-and-funding/fees-and-costs/), consumables/bench fee (£15,000 per annum) and living expenses during their stay in Liverpool.

Supervisors

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.