Barts Cancer Institute funded PhD studentship available for March 2019 start 

Application Deadline: 01 January 2019

Start Date: 01 March 2019

We are pleased to offer a fully funded PhD studentship starting in March 2019.

Our research training programme aims to develop a cohort of scientists equipped both intellectually and technically to conduct the highest quality cancer research.

Our research degrees are supplemented by a comprehensive support programme, providing training in a wide range of biomedical laboratory methods and other vital transferable skills.

ELUCIDATE THE ROLE OF MMR LOSS IN ENDOMETRIAL CANCER METASTASIS

Primary Supervisor: Dr Sarah-Anne Martin

Secondary SupervisorDr Emma Crosbie (University of Manchester)

Centre for Molecular Oncology

Project Outline:

Endometrial cancer (EC) is the 4th most common cancer in women and the most common gynaecological malignancy in the developed world. Although approximately 75% of patients present with early stage disease, 15-20% of these tumours recur after primary surgery. Outcomes for women with advanced or recurrent disease are extremely poor and the median survival in metastatic disease is only 7-12 months. Loss of the DNA mismatch repair pathway (MMR) is estimated to occur in approximately 30% of endometrial tumours. Whilst a small proportion of these are due to germline defects in one of the four MMR genes (MLH1, MSH2, MSH6 and PMS2), most result from epigenetic loss of MLH1. MMR deficiency is associated with well-established poor prognostic indicators in many studies of endometrioid EC, including high tumour grade, lymph node involvement, metastasis and recurrence. It has also been shown that that epigenetic MMR loss confers a worse prognosis than germline MMR loss. Currently, we do not know why this is the case and how this may impact on treatment approaches and survival outcome.

In this PhD studentship, we will dissect for the first time the specific molecular changes that occur in EC cells upon loss of function MLH1 mutation versus MLH1 methylation. To this end, we will use state-of-the-art CRISPR/Cas9 gene editing tools to directly mutate or methylate MLH1 in MMR-proficient normal primary endometrial cells. Using these models, we will determine whether mutation or methylation of MLH1 changes the ability of cells to metastasize. The MLH1mut and the MLH1meth cells will be analysed by whole-exome and RNA sequencing, to determine whether mutation or epigenetic loss of MLH1 leads to different mutator phenotypes and activation of distinct transcriptional programs.

 

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Who should apply

Academic Entry Requirements

These studentships are open to graduates with either:

  • a 2:1 or 1st degree in a related subject; or,
  • a 2:2 in a related subject with a subsequent MSc awarded with Merit or Distinction

For more information on international equivalencies please see here.

English Language Requirements

Applicants for whom English is not a first language will also require a minimum IELTS score of 6.5 (with 6.0 in the written component) or equivalent, unless your undergraduate degree was studied in, and awarded by, an English speaking country. For more information on acceptable English language qualifications please see here.

Fee Status

The funding for these studentships only covers tuition fees at the home/EU rate. Overseas applicants are welcome to apply, but will be required to fund the difference in tuition fees.

Funding

The studentship includes the following funding for 3 years:

  • A tax free annual stipend of £21,000
  • Tuition Fees at the Home/EU rate*
  • Project consumables

*If you are considered an overseas student for fee purposes, you are welcome to apply for this studentship, however you will be required to cover the difference in tuition fees.

How to apply

To apply you will need to complete an online application form.

The following supporting documents will be required as part of your application:

  • Your CV
  • Statement of purpose
  • Details of 2 referees
  • Copy of your transcript(s), including a breakdown of marks
  • Copy of your passport
  • If applicable, proof of English proficiency

Who to contact if you require further information

If you have a question about the project, or would like to arrange an informal discussion, please contact the supervisor directly. For general enquiries about the PhD studentship or application process please contact bci-cancercourses@qmul.ac.uk

What are the next steps in the application process?

The provisional interview date is Thursday 24 January 2019.

Successfully shortlisted candidates will be contacted a week before this date.

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