Short summary
The long-term survival of patients with acute myeloid leukaemia (AML) is poor. This project will determine how the expression of NFI (Nuclear Factor I) family members controls the development of leukaemia, by testing the effect of NFI proteins (or lack of) on blood cell development using a primary blood cell model. This knowledge will be used to develop more effective treatments for AML.
Project (Technical)
Given that the majority of abnormalities in AML are proteins of the nuclear compartment, we previously analysed the nuclear proteome of AML blasts in comparison with normal blood cells (CD34+) and identified upregulation of NFIC; 5.5 fold vs normal in 40% of the AML patient samples. Aberrant expression of this transcription factor is associated with several solid tumours but little is known about the role of NFIC or NFI family members in haematological malignancy including AML. We propose to explore the functional significance of NFI expression in AML pathogenesis and normal haematopoiesis. We will modulate levels of NFI family members in a human primary haematopoietic cell model and myeloid leukaemic cell lines to determine the functional consequences with respect to cell survival and proliferation. To gain further insight into the function of NFIC in blood cells, we will optimise CHIP protocols and perform ChIP sequencing against NFIC protein to identify potential DNA binding sites of NFIC and downstream target genes. A mechanistic understanding of how haematopoietic development is disrupted through NFI will lead to innovative approaches for therapeutic intervention.
Training environment
The student will be based in Cardiff’s Blood Cancer Research UK Centre of Excellence within the Section of Haematology, DCG. The main research interest of the Department is haematological oncology, which has consistently submitted an outstanding International Profile for the Research Excellence Framework assessments. The proposed supervisory team have a strong track record of research collaboration centred on understanding how molecular abnormalities associated with leukaemia contribute to disease pathogenesis. The proposed supervisors have been trained in supervision and have an excellent record of completion as well as progression of students to academic research.
Team
Prof Alex Tonks: Primary cell culture and overall project direction
Prof Richard Darley: Gene transduction and infection techqniues
Dr Steve Knapper: Clinical aspects of the project
Dr Hywel Williams: Bioinformatics
Keywords
AML, NF, targeted treatment, translational research
Application Process
We are seeking enthusiastic and motivated students with an interest in Cancer or genomic research. Applicants should possess a minimum of an upper second-class Honours degree, master's degree, or equivalent in a relevant subject.
Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS)
Following discussion with proposed supervisors and to be considered you must submit a formal application via Cardiff University’s online application service. Medicine - Study - Cardiff University
The total duration of this PhD programme is 3.5 years. There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (i.e. October 2022). This will take you to the application portal.
In the ‘Research Proposal’ section of the application enter the name of the project you are applying to.
Candidates must submit the following information:
- Supporting statement
- CV
- Qualification certificates
- Proof of Funding i.e. a letter of intent from your sponsor or confirmation of self-funded status.
- References x 2
- Proof of English language (if applicable)
Closing date for applicants is the 31st March 2022.
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