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School of Biological and Behavioural Sciences

Characterization of the evolution of DNA methylation readers across eukaryotes

The following fully-funded PhD studentship is available in the School of Biological and Behavioural Sciences with an expected start date of Sept 2023.

Research environment

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 laboratory of Alex de Mendoza works on the evolution of gene regulatory mechanisms, with a special interest on base modifications and transposable elements. The group has an expertise in comprative analysis of epigenetic profiles across distant eukaryotes, usually working on "non-model" systems. The group uses a combination of bioinformatics and cutting edge sequencing techniques to answer basic questions in genome evolution. You can find more information about the group here: https://www.demendozalab.com/.

This work would be done in collaboration with the Hurd laboratory (https://www.qmul.ac.uk/sbbs/staff/paulhurd.html), a leading group in epigenetics and chromatin biochemsitry. Both groups are part of the QMUL Epigenetics Hub, a highly dynamic network of laboratories with a wide range of expertise in epigenomics, see: http://qmulepigenetics.com/. 

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.

In this project, you will be trained in state-of-the-art comparative genomics and epigenomics (EM-seq, DAP-seq, high throughput proteomics) and molecular biology (cloning, nucleic acid extraction). You will get hands on experimental approaches and develop proficiency in computational and statistical analyses. In addition to focused training, you will be trained in project management and presentation skills and encouraged to develop international collaborations and networking, including attendance to national and/or international meetings.  

Project description

Cytosine DNA methylation is one of the most studied epigenetic marks in eukaryotes, with established roles in genome regulation and selfish DNA silencing. Still, we do not fully understand how methylation influences transcription. In part, that limitation is linked to the widespread focus on few highly complex model systems, mostly mammals or plants, with highly complex methylation patterns. In this project we want to fill this gap by understanding the evolution of cytosine methylation “readers”, proteins capable of exclusively binding to methylated cytosines. To this end, we will use comparative genomics and proteomics on multiple eukaryotes with simpler methylation landscapes, occupying key positions in the tree of life. The proteins identified in the previous approach will be then validated using functional genomics (e.g. DAP-seq, ChIP-seq).

This project will reveal how the various gene families that are known to have roles in DNA methylation interpretation evolved, and potentially will discover new proteins with this capacity. Ultimately, understanding how eukaryotic genomes interpret DNA methylation is important to clarify the roles of this epigenetic mark in genome regulation. In turn, these findings will have applications in synthetic biology approaches. Given the key roles DNA methylation has in human disease, including cancer, an evolutionary-informed mechanistic understanding of this epigenetic mark is critical, as the various genes and mechanisms we learn in divergent eukaryotes can be then used to read and interpret our own epigenome.  

Funding

This studentship is open to Home Fee applicants and is funded by an ERC Starting Grant. It will cover tuition fees at the home rate, and provide an annual tax-free maintenance allowance for 3 years at the Research Council rate (£19,668 in 2022/23).

Eligibility and applying

Applicants must be:

- UK residents or have pre-settled or settled status.

- EU nationals: consult with the supervisor Alex de Mendoza at a.demendozasoler@qmul.ac.uk

Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree and a masters degree in an area relevant to the project (Molecular Biology, Bioinformatics, Biochemistry). A masters degree is highly desirable, but not essential.

For this PhD, any previous experience on molecular biology work, from cloning to protein purification would be highly benefitial. Furthermore, some basic knowledge of bioinformatics would also be helpful, although we are happy to provide training on this aspect. The project would combine wet lab and bioinformatics.

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 Alex de Mendoza at a.demendozasoler@qmul.ac.uk. Formal applications must be submitted through our online form by 15th June 2023 for consideration, including a CV, personal statement and qualifications. 

Shortlisted applicants will be invited for a formal interview by the project supervisor.

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/ 

Apply Online

References

  1. Capture of a functionally active Methyl-CpG Binding Domain by an arthropod retrotransposon family.
    de Mendoza A, Pflueger J, Lister R. Genome Research. 29(8):1277-1286. 
  2. Evolution of DNA methylome diversity in eukaryotes
    A de Mendoza, R Lister, O Bogdanovic. Journal of molecular biology 432 (6), 1687-1705
  3. The emergence of the brain non-CpG methylation system in vertebrates.
    A de Mendoza, D Poppe, S Buckberry, J Pflueger, CB Albertin, T Daish, et al.
    Nature ecology & evolution 5 (3), 369-378
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