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Development of LSD1 (KDM1a)/CoREST Targeting Strategies for the Treatment of Poor Prognosis Cancers


Project Description

This studentship will provide experience in both a medicinal chemistry and cancer biology lab. It will provide excellent training across a range of skills and create an excellent platform for a cutting edge academic research career.

The TBX2-CST6 pathway is frequently modified in many human cancers, with upregulation of TBX2 and loss of CST6 being observed in poor prognosis cancers, such as breast, prostate and pancreatic. Our research has also shown that LSD1 (KDM1a, an epigenetic enzyme) knock down can modulate this pathway leading to an upregulation of CST6 leading to cancer cell kill, whilst sparing normal cell lines. Targeting of LSD1 could provide a new and very powerful therapeutic option to treat these cancers. However, despite a number of LSD1 inhibitors being developed for the treatment of melanoma and leukaemia, our research has shown that these catalytic inhibitors have little or no impact on CST6 or cancer cell lines from other cancer types. To circumvent this issue we aim to develop an LSD1 targeting PROTAC (Protein Targeting Chimeras). PROTACs have been shown to degrade the target protein, rather directly inhibit it, via the recruitment of an E3 ligase which polyubiquinates the protein. The polyubiquinated protein is then sequestered to the proteasome and destroyed. This approach, which replicate biological knock out effects, has seen a number of clinically relevant drugs enter clinic trials.

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 Cancer Research and Cell Biology, website for further details about the Centre:

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

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

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