The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2021 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 180 PhD students working on projects in the biological and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services.
The Busch lab (buschlab.org) uses the zebrafish model to investigate the gene-regulatory underpinnings of development and disease with a focus on phenotypic robustness. We employ a combination of functional genomics, bioinformatics and in vivo approaches taking advantage of our large collection of zebrafish mutants. The group of co-supervisor Paul Hurd has extensive experience in epigenetics and applies state-of-the-art high-throughput sequencing techniques.
Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career.
The PhD student will gain experience in a broad range of molecular techniques (high-throuput sequencing techniques such as ATAC-seq and CUT&RUN, CRISPR/Cas9, cloning, transgenesis, immunohistochemistry, in situ hybridisation) and bioinformatics (gene expression analysis, genomics, command line programming, data analysis and visualisation using R).
This project will investigate the role of epigenetics and chromatin maintenance in cancer using cutting-edge functional genomics approaches and in vivo phenotyping techniques.
We have previously demonstrated that loss-of-function of the heterochromatin modifier Kdm2aa, a H3K36me2 demethylase and an interaction partner of Heterochromatin Protein 1 (HP1), causes melanoma and potentially other cancers in zebrafish. RNA-seq analysis in mutant larvae shows that already a few days after fertilisation DNA damage repair pathways are dysregulated. Likewise we find that DNA damage signalling seems to be reduced in Kdm2aa homozygous mutants. In addition, a group of genes, normally silenced and located in a large heterochromatic genomic region, is de-repressed suggesting defects in heterochromatin maintenance.
In this project we will take advantage of zebrafish genetics (our mutant library of 40,000 alleles and CRISPR/Cas9) and transgenesis in combination with cutting-edge molecular biology, functional assays and genomics techniques.Aim 1: Which protein domains are responsible for the melanoma phenotype? Kdm2aa has several protein domains that facilitate its interaction with HP1 and its demethylase activity. We have shown previously, that only the HP1 interaction domain, but not the demethylase activity is required for an overexpression phenotype in zebrafish. We will use CRISPR/Cas9 and homology-driven repair to specifically generate Kdm2aa domain mutants to identify which domains are required to prevent melanoma formation.Aim 2: Which DNA damage repair pathways are affected by Kdm2aa LoF? RNA-seq data suggests a downregulation of the double-strand break response. We will use antibodies and transgenic lines to investigate where in the DNA damage signalling and repair hierarchy Kdm2aa is required.Aim3: How does chromatin change in Kdm2aa mutant derived cancers? We will use ATAC-seq and CUT&RUN sequencing to uncover the underlying chromatin changes in hyper-migratory melanocytes and melanoma.
This studentship is open to students applying for CONACyT funding. CONACyT will provide a contribution towards your tuition fees each year and Queen Mary will waive the remaining fee. CONACyT will pay a stipend towards living costs to its scholars. Further information can be found here: https://conacyt.mx/convocatorias/convocatorias-becas-al-extranjero/
Please refer to the CONACyT website here: https://conacyt.mx/convocatorias/convocatorias-becas-al-extranjero/ for full details on eligibility and conditions on the scholarship.
Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree in an area relevant to the project, such as biological or biomedical sciences or medical genetics. A masters degree is desirable, but not essential.
Previous experience working with model organisms and/or large-scale datasets is desirable, but not essential.
Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our English language requirements page for details: https://www.qmul.ac.uk/international-students/englishlanguagerequirements/postgraduateresearch/
Informal enquiries about the project can be sent to Elisabeth Busch-Nentwich at e.busch-nentwich@qmul.ac.uk
Applicants will need to complete an online application form to be considered, including a CV, personal statement and qualifications. Shortlisted applicants will be invited for a formal interview by the project supervisor. Those who are successful in their application for our PhD programme will be issued with an offer letter which is conditional on securing a CONACyT scholarship (as well as any academic conditions still required to meet our entry requirements).
Once applicants have obtained their offer letter from Queen Mary they should then apply to CONACyT for the scholarship as per their requirements and deadlines, with the support of the project supervisor.
Only applicants who are successful in their application to CONACyT can be issued an unconditional offer and enrol on our PhD programme.
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