The role of ALMS1 in human pancreatic beta cell development and function


   Institute of Metabolism and Systems Research

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  Dr Gabriela da Silva Xavier, Dr I Akerman, Prof Tarekegn G Hiwot  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Additional supervisor: Dr. Nick Hannan, University of Nottingham

Informal enquiries should be directed to the project supervisor Dr Gabriela da Silva Xavier [Email Address Removed]

Person Specification

Applicants should have a strong background in cell biology, and ideally a background in physiology. They should have a commitment to biomedical research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a subject related to the biomedical sciences.

Project Details:

Want to make a difference? Want to engage with cutting edge research and gain skills that will be highly sought after? 

This PhD project will suit a candidate who is driven to search for a cure for a rare disease called Alström syndrome for which there is currently no disease modifying treatment. As a PhD student you will extend our preliminary work on human pancreatic beta-cells (the cells that make insulin), which indicate that beta-cell dysfunction is a primary defect in Alström syndrome and could lead to many of the complications observed in patients living with Alström syndrome. 

 You will generate a human embryonic stem cell line using CRISPR-CAS9 technology to model Alström syndrome. You will apply a cell differentiation protocol, to generate pancreatic beta-cells. You will use these beta-cells to dissect the mechanisms through which Alström syndrome affects function, using a combination of biochemical and cell biology techniques, cutting edge microscopy, and next generation sequencing to assess cell function and differentiation status. You will then assess the efficacy of small molecules to correct dysfunction. All of this whilst working with experts in the techniques you will be using, based at the Universities of Birmingham and Nottingham.  

To apply:

Click on the institutional link which will take you to the MRC AIM website which contains full information and the application forms.

Please ensure your application is submitted by the deadline of midday (GMT) Friday 12 January 2024 as late applications will not be considered.

Biological Sciences (4) Engineering (12) Medicine (26)

Funding Notes

This is a fully funded studentship provided by the Medical Research Council.
If you are successful, you will receive a stipend (currently £18,622 per year for 2023/24) and a tuition fee waiver for 4 years.
Successful candidates will also receive an allowance for a laptop, a travel and conference allowance and an allowance for laboratory/PhD running costs.

References

1. Marshall, J. D., Muller, J., Collin, G. B., Milan, G., Kingsmore, S. F., Dinwiddie, D., Farrow, E. G., Miller, N. A., Favaretto, F., Maffei, P., Dollfus, H., Vettor, R., and Naggert, J. K. (2015) Alstrom Syndrome: Mutation Spectrum of ALMS1. Hum Mutat 36, 660-668
2. Hearn, T. (2019) ALMS1 and Alstrom syndrome: a recessive form of metabolic, neurosensory and cardiac deficits. J Mol Med (Berl) 97, 1-17
3. Nesmith, J. E., Hostelley, T. L., Leitch, C. C., Matern, M. S., Sethna, S., McFarland, R., Lodh, S., Westlake, C. J., Hertzano, R., Ahmed, Z. M., and Zaghloul, N. A. (2019) Genomic knockout of alms1 in zebrafish recapitulates Alstrom syndrome and provides insight into metabolic phenotypes. Hum Mol Genet 28, 2212-2223
4. Nair, G. G., Liu, J. S., Russ, H. A., Tran, S., Saxton, M. S., Chen, R., Juang, C., Li, M. L., Nguyen, V. Q., Giacometti, S., Puri, S., Xing, Y., Wang, Y., Szot, G. L., Oberholzer, J., Bhushan, A., and Hebrok, M. (2019) Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived beta cells. Nat Cell Biol 21, 263-274
5. Russ, H. A., Parent, A. V., Ringler, J. J., Hennings, T. G., Nair, G. G., Shveygert, M., Guo, T., Puri, S., Haataja, L., Cirulli, V., Blelloch, R., Szot, G. L., Arvan, P., and Hebrok, M. (2015) Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. Embo J 34, 1759-1772

Where will I study?