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(MCRC Non-Clinical) Investigating the role of LGALS1 as a novel therapeutic target in CMML


Faculty of Biology, Medicine and Health

About the Project

Chronic myelomonocytic leukaemia (CMML) is a haematological neoplasm with dismal prognosis and no effective treatment options. Single cell RNA-sequencing followed by targeted q-RT-PCR on disease-initiating stem cells from CMML patients and healthy controls revealed elevated levels of LGALS1 in CMML patients. LGALS1 encodes the carbohydrate-binding protein Galectin-1, which is also overexpressed in other haematological malignancies including CML, AML, and multiple myeloma. Although LGALS1 levels have been correlated with poor prognosis in several malignancies the mechanisms leading to LGALS1 overexpression, and whether LGALS1 could be a therapeutic target in CMML, have not been evaluated. Our preliminary data suggest that targeting LGALS1 using shRNA or small molecule inhibitors has a cytostatic effect on CMML stem and progenitor cells. The prospective student will further investigate: 1) the effect of targeting the LGALS1-axis on CMML cell survival; 2) the molecular mechanism involved in LGALS1 mediated cell survival; and 3) upstream pathways responsible for the induction of LGALS1 in CMML patient samples. Data from this study will be used to establish for the first time LGALS1 as a therapeutic target against CMML stem cells.

Entry Requirements:
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage.

UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the CRUK Manchester Centre PhD Training Scheme (MCRC) website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/

General enquiries can be directed to .

Equality, diversity and inclusion is fundamental to the success of The University of Manchester and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Interview date – 8 January 2021

Funding Notes

Funding will cover UK tuition fees/stipend only (currently at £19,000 per annum) and running expenses. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable a limited number of full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

The duration of this project is four years commencing October 2021.

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