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Identifying the role of inflammasome in human MS


Project Description

Successful long-term tissue regeneration of any organ beyond the experimental state remains elusive. Given that the immune system plays a key role in tissue regeneration, including in the CNS, one of the most promising approaches is to integrate endogenous immune mechanisms into regenerative strategies, provided appropriate timing and resolution of inflammation. Consequently specific knowledge of the fundamental cross-talk between immune mechanisms and the regenerating tissue is needed.
In multiple sclerosis (MS), myelin, the coating around neuronal axons is destroyed resulting in neurodegeneration. Damaged myelin can be functionally reinstated by remyelination that involves recruitment, proliferation and differentiation of oligodendrocyte progenitor cells (OPC), generation of new myelin by differentiated oligodendrocytes and the re-sheathing of nerve fibres with new myelin. To date we have no means to enhance remyelination and prevent neurodegeneration. Using immune mechanisms to stimulate this regenerative cascade could be a novel way to overcome this block and boost remyelination.

We have demonstrated that inflammasomes and their products IL-1beta (IL-1b) and IL-18 are key modulators of oligodendrocytes and myelin generation in animal models of MS. This PhD project is the next step in identifying immune targets to modulate myelin regeneration by translating our findings from the mouse to the human system. We hypothesise that inflammasomes are present in human MS tissue and that inflammasome products IL-1b and IL-18 modulate myelin generation of human oligodendrocytes.
The aim of this study is to determine the function of inflammasomes and their products in human MS using human post mortem MS tissue and human oligodendrocytes.

Specific aim 1 (months 1-24)
To characterise the expression of inflammasome markers in different forms of human MS tissue (relapsing-remitting vs progressive, acute vs chronic, regenerating vs non-regenerating) to identify any differences in their inflammasome profile.
Specific aim 2 (months 13-36)
To identify the function of inflammasome products IL-1b and IL-18 in myelin generation of human oligodendrocytes to determine if they are potential targets to modulate myelin production similar to our murine models.

ENTRY REQUIREMENTS

Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant biomedical or life sciences subject.

English Language

Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.

The minimum recommended score for the School of Medicine, Dentistry and Biomedical Science is:
• IELTS score of 6.0 with not less than 5.5 in each of the four component elements of listening, reading, speaking and writing taken within the last 2 years;
• TOEFL score of 80+ (internet basted test), taken within the last 2 years, with minimum component scores of; Listening 17, Reading 18, Speaking 20, Writing 17);
• A valid Certificate of Proficiency in English grade A or B;
• A valid Certificate of Advanced English grade A; or
• A first or upper second class honours degree from a university based in the UK, Republic of Ireland or other suitably quality assured location in a country deemed by the UK Border Agency to be majority English speaking.

For a list of English Language qualifications also accepted by the School and University please see the following link:
http://www.qub.ac.uk/International/International-students/Applying/English-language-requirements/#English

INTO Queen’s English Language Courses offers both pre-sessional and in-sessional courses in English for academic purposes and study skills. Courses vary in length and full information can be obtained at: https://www.qub.ac.uk/International/International-students/Applying/University-Preparation-Courses/INTOEnglishlanguagecoursesatQueens/

Funding Notes

*FUNDING CONFIRMED – Department for the Economy (DfE) Award*

Eligibility for both fees (£4,327 for 2019/20, 2020/21 TBC) and maintenance (£15,009 for 2019/20, 2020/21 TBC) depends on the applicants being either an ordinary UK resident or those EU residents who have lived permanently in the UK for the 3 years immediately preceding the start of the studentship.

Non UK residents who hold EU residency may also apply but if successful may receive fees only.

For further details re eligibility criteria (including academic, citizenship and residency criteria) please click on the following link: View Website

References

Please visit the School of Medicine, Dentistry and Biomedical Sciences, Centre for Experimental Medicine, website for further details about the Centre:

http://www.qub.ac.uk/research-centres/CEM/

When applying, please choose 'MEDICINE' as your subject area/School.

Dombrowski homepage http://go.qub.ac.uk/yvonnedombrowski
DombrowskiLab Facebook: https://en-gb.facebook.com/thedombrowskilab/
Twitter: @DombrowskiLab & @DombrowskiQUB

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