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Novel drug target validation for treating Diabetes Mellitus (ref: SF18/APP/Soundararajan)


Project Description

The important cellular entities responsible for fighting against infections in our body are the T cells. T cells are however also shown to play a central role in the development of autoimmune diseases (AIDs) as “T cell activation hijacking” is the major autoimmune reaction causing mechanism observed in several AIDs. DRAK2 belonging to cell death inducing kinase family is shown to control sensitivity towards T cell receptor mediated activation and signalling. Drak2 has been implicated as a central player in type I and type II Diabetes and demyelination disease of human Multiple Sclerosis. Various gene knockdown studies in animal models suggest DRAK2 could be a central regulator of autoimmune responses.
Therefore, in-vitro approaches to identify and validate small molecule inhibitors that specifically target DRAK2 will be hugely beneficial to further test them in various model systems and develop new therapeutics for autoimmune ¬¬disorders. This project will focus on identifying novel inhibitor for DRAK2 that control T cell mediated autoimmune responses. The project involves screening for small molecules that specifically target DRAK2 using in-vitro assays and validating the function in mammalian cell cultures. Further the cellular signalling pathways modulated during this process will be studied through large scale proteomic approaches. Mammalian cell culture facility and Tecan Spark 10M are already set up for cell biology work which will facilitate enzymatic and cell analysis respectively. Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometers in-house is dedicated for omics high throughput profiling to understand the cellular functions and molecular interactors of DRAK2 during T-cell mediated immune responses.

Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed. Applications that do not include the advert reference (e.g. SF18/…) will not be considered.

Deadline for applications: 1st July 2019 for October 2019 start, or 1st December 2018 for March 2019 start
Start Date: October or March

Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality and is a member of the Euraxess network, which delivers information and support to professional researchers

Funding Notes

This studentship is only open to self-funding candidates. Self-funding candidates are expected to pay University fees and to provide their own living costs. University fee bands are shown at
View Website
Projects in Applied Sciences are typically costed at Band 3 or Band 4.

References

Proteomics and Bioinformatics analysis identifies novel cellular roles outside mitochondrial function for human Miro GTPases. Laura J. Kay, Vartul Sangal, Gary W. Black and Meera Soundararajan. Molecular and Cellular Biochemistry. DOI:10.1007/s11010-018-3389-6

Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition. Soundararajan M, Roos AK, Savitsky P, Filippakopoulos P, Kettenbach AN, Olsen JV, Gerber SA, Eswaran J, Knapp S, Elkins JM. Structure. 2013 Jun 4;21(6):986-96

Novel Inverse Binding Mode of Indirubin Derivatives Yields Improved Selectivity for DYRK Kinases.
Myrianthopoulos V, Kritsanida M, Gaboriaud-Kolar N, Magiatis P, Ferandin Y, Durieu E, Lozach O, Cappel D, Soundararajan M, Filippakopoulos P, Sherman W, Knapp S, Meijer L, Mikros E, Skaltsounis AL. ACS Med Chem Lett. 2013 Jan 10;4(1):22-26.

Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.
Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak MS, Kwon M, Choi HG, Sim T, Deveraux QL, Rottmann S, Pellman D, Shah JV, Kops GJ, Knapp S, Gray NS.
Nat Chem Biol. 2010 May;6(5):359-68. doi: 10.1038/nchembio.345.

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