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Funded PhD Opportunity

Identifying molecular dependencies in NRAS-mutant leukaemia

Subject: Biomedical Sciences


Summary

Acute myeloid leukaemia (AML) is a type of blood cancer of myeloid lineage that is characterised by the rapid proliferation and accumulation of immature cells in the bone marrow. There are approximately 3,100 new cases of AML diagnosed in the UK each year and 2,600 deaths1. Recent whole genome sequencing efforts in both childhood2 and adult3 AML have defined the driver landscape in the disease which will further support patient stratification and targeted drug development.

Oncogenic mutations in NRAS are highly prevalent in AML, especially in the paediatric disease (~30% of cases) compared to adult AML (~10%), despite the low somatic mutational burden2. NRAS normally functions by transducing signals from activated receptors to the nucleus, where it regulates cell growth and survival. Mutant NRAS encodes a protein which is locked in the ‘on’ conformation, resulting in sustained growth and survival of the leukemic cells. While representing an exciting therapeutic target, directly targeting oncogenic NRAS, or any of the Ras family members, is complex and no clinical inhibitors currently exist4.

This PhD studentship aims to identify genes that mutant NRAS may depend on for survival and understand their role in the development of AML. To do this, the student will first investigate molecular exclusivities with mutant NRAS that have recently been identified as part of the Beat AML programme2. The student will then perform a genome-wide synthetic lethality screen using CRISPR-Cas9 technology in clinically relevant NRAS mutant cell models to identify genes, that when knocked out, result in the death of NRAS mutant AML cells. Genes that are essential for the survival of NRAS mutant AML cells will be validated and studied in a variety of murine and human models and in patient samples.

The overall aim is to identify molecular dependencies in NRAS-driven leukaemia that may present an alternative therapeutic strategy to directly targeting mutant NRAS. This project and will benefit from a range of approaches, such as CRISPR-Cas9 knockout screening, molecular biology, genomics, FACS, computational biology and murine models.

References

1 Cancer Research UK.

2 Bolouri et al. 2018. Nature Medicine, 24:103-112.

3 Tyner et al. 2018. Nature, 562: 526-530.

4 Downward 2015. Clinical Cancer Research, 21:1802-1809.


Essential criteria

  • Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC)
  • Sound understanding of subject area as evidenced by a comprehensive research proposal

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • First Class Honours (1st) Degree
  • Masters at 65%
  • Research project completion within taught Masters degree or MRES
  • Practice-based research experience and/or dissemination
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings
  • A comprehensive and articulate personal statement
  • Relevant professional qualification and/or a Degree in a Health or Health related area

Funding

    The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:

    Vice Chancellors Research Studentship (VCRS)

    Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant per annum for three years (subject to satisfactory academic performance). This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Vice-Chancellor’s Research Bursary (VCRB)

    Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant per annum for three years (subject to satisfactory academic performance). This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Vice-Chancellor’s Research Fees Bursary (VCRFB)

    Fees only award (PhD fees + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance). This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Department for the Economy (DFE)

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 15,009 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies


Other information


The Doctoral College at Ulster University


Reviews

My experience has been great and the people that I have worked with have been amazing

Kieran O'Donnell - 3D printing of biological cells for tissue engineering applications

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Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.

Michelle Clements Clements - MRes - Life and Health Sciences

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Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.

William Crowe


Key dates

Submission deadline
Monday 18 February 2019

Interview Date
w/c 11, 18 and 25th March 2019


Applying

Apply Online  


Campus

Magee campus

Magee campus
A key player in the economy of the north west


Contact supervisor

Dr Kyle Matchett


Other supervisors

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