Dr S Woolner, Dr S Banka, Dr T Millard, Prof Viki Allan
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
RAC1 regulates a variety of cellular functions essential for normal development1,2,3. We recently discovered a novel genetic disease ‘RAC1-related neurodevelopmental disorder’ (RRND)4. Other developmental disorders caused by mutations in genes encoding proteins that interact with RAC1 have been recently identified and there is evidence that some of these conditions could be amenable to treatment5,6. Understanding the mechanisms underlying the phenotype of RAC1-related disease is required to develop treatments for RRND and related diseases.
In addition, our ongoing studies point towards the existence of a different class of cryptic mutations involving RAC1 which cause another novel disease ‘RAC1-related malformation syndrome (RRMS)’.
In this project the student will -
1. Identify the disease mechanism of RRND at the molecular, cellular and organismal levels using Xenopus, fruit flies and patient cells.
2. Identify potential treatments for RRND.
3. Identify the genetic basis of RRMS by performing genomic studies on DNA samples of patients with RRMS.
This is an inter-disciplinary project that will equip an excellent candidate with a range of skills that will be useful in several areas of biological and medical sciences. The project will provide a solid foundation in disease-gene discovery, understanding disease mechanisms and development of new treatments.
In addition to a vast suit of technical skills, the student will benefit from being supervised by a team composed of basic scientists and a clinical academic who will bring complementary areas of expertise. Each of the supervisors has active research programmes and this will expose the student to a breadth and depth of biomedical research that is usually very difficult to find in a project set in a single laboratory.
https://www.research.manchester.ac.uk/portal/sarah.woolner.html
https://www.research.manchester.ac.uk/portal/siddharth.banka.html
https://www.research.manchester.ac.uk/portal/tom.millard.html
https://www.research.manchester.ac.uk/portal/viki.allan.html
Entry Requirements
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
Funding Notes
This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
References
1. Duquette, P. M. & Lamarche-Vane, N. Rho GTPases in embryonic development. Small GTPases 5 e972857 (2014).
2. Ng, J. et al. Rac GTPases control axon growth, guidance and branching. Nature 416 442–447 (2002).
3. Woolner S, Jacinto A, Martin P. The small GTPase Rac plays multiple roles in epithelial sheet fusion--dynamic studies of Drosophila dorsal closure. Dev Biol. 282 163-73. (2005)
4. Reijnders, M. R. F. et al. RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes. The American Journal of Human Genetics 101, 466–477 (2017).
5. Hollstein, R. et al. HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome. J Med Genet 52 797-803 (2015)
6. Marei, H. & Malliri, A. Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms. Small GTPases 8 139-163 (2016).
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