Investigating the rules of paralogue interactions during embryonic development

The folllowing fully-funded PhD studentship is available in the School of Biological and Behavioural Sciences with an expected start date of April or September 2022.

Research environment

The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2014 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 150 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 bioinformatics and in vivo approaches, taking advantage of our large collection of zebrafish mutants.

Training and development

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 (CRISPR/Cas9, cloning, transgenesis, immunohistochemistry, in situ hybridisation) and bioinformatics (gene expression analysis, genomics, command line programming, data analysis and visualisation using R).

Project details

Embryonic development is an intricate process governed by gene-regulatory interactions that occur with spatial and temporal precision. Given the complexity, it can seem surprising how rarely this process goes awry even when gene function is lost. One mechanism that ensures the smooth progression of development is genetic compensation between paralogue pairs, where one gene can take over the lost function of another. This compensation can be reciprocal, or sometimes only one gene can replace the other, but not vice versa. At present, these interactions are impossible to predict since the underlying rules are not well understood. The zebrafish is the ideal model system to investigate this phenomenon owing to a whole genome duplication (WGD) in the teleost lineage that occurred in addition to the two WGDs shared with humans. Functional comparisons of the more recent zebrafish-specific paralogue pairs with ancestral duplications will reveal crucial insights into the evolution and grammar of paralogue interactions.

The successful candidate will use bioinformatics and functional in vivo approaches to investigate and classify zebrafish paralogues. The bioinformatics part will include comprehensive cross-species comparisons to identify different classes of paralogues (e.g. based on divergence of spatio-temporal expression, sequence similarity and other gene features) taking advantage of resources such as Ensembl, ZFIN and large-scale gene expression datasets. Functional work in vivo using CRISPR/Cas9, our mutant archive (https://zmp.buschlab.org/), transgenic overexpression and phenotypic analysis will test hypotheses formed by the genomic work.

Through this project the candidate will gain extensive experience in large-scale data analysis and thorough training in state-of-the-art molecular and experimental biology.

Eligibility and applying

Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class bachelors degree, or equivalent qualification, in biological sciences. A Master's degreee is desirable, but not essential.

Previous experience working with model organisms 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 Dr Elisabeth Busch-Nentwich ([Email Address Removed]). Formal applications must be submitted through our online form by the stated deadline including a CV, personal statement and qualifications. A research proposal is not required.

The School of Biological and Behavioural Sciences is committed to promoting diversity in science; we have been awarded an Athena Swan Silver Award. We positively welcome applications from underrepresented groups.

http://hr.qmul.ac.uk/equality/

https://www.qmul.ac.uk/sbcs/about-us/athenaswan/