PhD Studentship: Dissecting the Role of the DNA Damage Response in Leukaemogenesis in a Zebrafish Model of GATA2 Deficiency

Job Overview

Location
Birmingham, England
Job Type
Full Time
Date Posted
1 month ago

Additional Details

Job ID
10755
Job Views
77

Job Description

University of Birmingham - Institute of Cancer and Genomics Sciences

Qualification Type:PhD
Location:Birmingham
Funding for:UK Students
Funding amount:Not Specified
Hours:Full Time
Placed On:16th February 2021
Closes:12th March 2021


Applications are invited for a non-clinical PhD studentship at the Cancer Research UK (CRUK) Birmingham Centre.

The blood cells that carry oxygen, heal wounds and fight infections in our bodies arise from blood stem cells in our bone marrow. Errors (or mutations) in crucial blood stem cell genes can lead to blood disorders. Mutations in the GATA2 gene lead to a disorder called GATA2 deficiency. GATA2 haploinsufficiency drives bone marrow failure that progresses to myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) at a median age of 20. The mechanisms underlying disease progression and leukaemogenesis in these patients are unknown. In this project, the student will use a combination of in vitro technologies to study DNA damage repair (DDR) in haematopoietic progenitor cells and genetics and genomics in an in vivo zebrafish disease model to investigate how GATA2 protects against genomic instability and the appearance of secondary mutations that eventually lead to leukaemogenesis.

The Monteiro Lab (https://www.birmingham.ac.uk/staff/profiles/cancer-genomic/monteiro-rui.aspx) studies the fundamental mechanisms underpinning haematopoiesis in development and homeostasis and how perturbations in these mechanisms lead to haematopoietic disease. They have leveraged their expertise in developmental haematopoiesis (Monteiro et al., EMBO J, 2011; Monteiro et al., Dev Cell, 2016; Dobrzycki et al., Biol Open, 2018) and genetics (Bonkhofer et al., Nature Comms, 2019) to generate a zebrafish model with GATA2 deficiency characteristics (Comms Biol, 2020). This project aims to combine the expertise of the Monteiro lab with that of the Higgs lab (DNA damage; https://www.birmingham.ac.uk/research/cancer-genomics/research/lysine-methylation-dna-damage/index.aspx) and Stankovic lab (translational haematopoesis; https://www.birmingham.ac.uk/research/cancer-genomics/research/haematopoietic-malignancies/index.aspx) to investigate the link between transcriptional regulation, the DDR and leukaemogenesis to help identify strategies to prevent or delay disease progression in the zebrafish model and pave the way towards better patient stratification in humans.

The successful applicant will have experience in laboratory research and will be highly motivated and ambitious. They will have a collegiate mind set, and as well as benefitting from the diverse expertise, resources and opportunities the Centre studentship programme has to offer, they will be willing to work in partnership with Centre colleagues to promote and publicise the research of the Centre. As part of this, the studentship will provide opportunities for science engagement activities in the cancer area.

Applicants should have a First or Upper Second Class Honours Degree in a relevant subject, and some experience of working in a laboratory. Previous experience with zebrafish, haematopoiesis or single cell technologies are desirable but not essential. They should have a strong commitment to research, strong interpersonal skills, and a willingness to take part in public engagement activities. Additionally, non-UK applicants must provide evidence that they can self-fund the difference between home and international tuition fees.

Informal enquiries should be directed to Dr Rui Monteiro ([email protected]). Applications should be directed to Claire Fenlon ([email protected]).

To apply, please send:

  • A detailed CV;
  • Names and addresses of two referees, ideally who have supervised your laboratory research;
  • A personal statement highlighting your research experience/capabilities and your reasons for applying for a PhD studentship at the Cancer Research UK Birmingham Centre;
  • Copies of your degree certificates with transcripts;
  • Evidence of your proficiency in the English language, if applicable.

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