19/01/2018

PhD in Cancer and Genetics: Transcription factor dysregulation in acute myeloid leukaemia and blood cancers

This job offer has expired


  • ORGANISATION/COMPANY
    Cardiff University
  • RESEARCH FIELD
    Medical sciences
  • RESEARCHER PROFILE
    First Stage Researcher (R1)
  • APPLICATION DEADLINE
    13/02/2018 12:00 - Europe/London
  • LOCATION
    United Kingdom › Cardiff
  • TYPE OF CONTRACT
    Temporary
  • JOB STATUS
    Full-time
  • HOURS PER WEEK
    35
  • OFFER STARTING DATE
    01/04/2018

Acute myeloid leukaemia (AML; a form of blood cancer) is a difficult to treat disease with poor long-term survival of patients.

The RUNX1-ETO fusion gene is one of the most frequent abnormalities associated with this disease (12% of all AML.) However, its role in the pathogenesis of AML remains poorly understood and the only prospect for improved outcomes is the development of targeting treatments. Previously we devised an experimental model based on normal human primary haematopoietic cells which enabled us to analyse the effects of RUNX1-ETO on blood cell development. These studies published in leading haematological malignancy journals (Blood and Leukemia) showed that this fusion gene was able to inhibit the development of haematopoeitic cells and also promote the growth of immature blood cells – the hallmarks of AML.

Aims

We now propose to extend our earlier RUNX1-ETO studies by analysing relative abundance of transcription factor proteins in the nuclei of RUNX1-ETO expressing cells using proteomic analysis. It will be determined if there are consistent patterns of dysregulation in RUNX1-ETO cells compared with normal haematopoietic blasts.

This is is an ambitious, interdisciplinary, state of the art project combining quantitative proteomics (for the first time in RUNX1-ETO expressing cells) with nuclear protein expression in human primary cells. This project builds on substantial preliminary findings and will use a range of techniques ranging from molecular biology to developmental cell biology of stem cells. The project will involve genetic modification of blood stem cells and leukaemia cell lines to study the impact on their subsequent growth and development.

Benefits

This work forms part of an on-going programme of study with several high impact factor papers already published. You will be in a good position to quickly generate high impact factor publications during the course of this PhD and become competitive for post-doctoral positions. The project covers a range of established and cutting edge techniques giving you a thorough grounding in the developmental biology of stem cells (cell and protein analysis) as well as providing experience in the relatively new technique of gene editing (e.g. CRISPR).

Supervisory team

The supervisory team currently has a 100% success rate within 4 years. Our students are encouraged to promote their scientific development; formulating their own ideas, hypotheses and experimental plans. This is evidenced by the fact that all our past students, have been employed as post-doctoral scientists or have become principal investigators in their own right.

The work will be supervised by a trained and experienced supervisory team with a track record of successful outcome in an excellent research environment for the study of blood cancer; joining an immediate group of 10 researchers and supported by approximately 30 scientists department wide. This research may allow current therapy to be more effective and therefore reduce the overall healthcare burden of this disease.

The Research Centre

Cardiff University has an excellent programme to support postgraduate research students. You will be based in Cardiff’s Bloodwise (formerly LLR) Centre of Excellence and the research will complement the currently funded Cancer Research Wales, Tenovus Cancer Care Projects as well as Bloodwise specialist programmes. The student will be hosted within the Section of Haematology which lies within the Division of Cancer and Genetics at Cardiff University and is one of the largest centres for the study of blood diseases in the UK.

The main research interest of the Section is haematological oncology, which has consistently submitted an outstanding International Profile for the RAE/REF assessments. The Section of Haematology itself has funding exceeding £5 million including the CRUK/DoH funded ECMC and 2 Bloodwise funded specialist programmes (>£1M). We host phase I/II trials and lies at the hub of the MRC-Bloodwise-NCRI AML trials network, with excess patient material obtained at diagnosis from patients entering the AML14-20 studies from centres throughout the UK available for use in the proposed project.

Benefits

Doctoral stipend matching UK Research Council National Minimum

Offer Requirements

Skills/Qualifications

You will hold or expect to achieve a First or Upper Second Class degree in a relevant area, such as Medicine, Biology or Biomedical Sciences.

Specific Requirements

Open to all UK/EU students without further restrictions

Work location(s)
1 position(s) available at
Cardiff University
United Kingdom
Cardiff

EURAXESS offer ID: 272959