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Detecting base modifications in dinoflagellates using Nanopore sequencing


   School of Biological and Behavioural Sciences

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  Dr Alexandre de Mendoza, Prof Vardham Rakyan  No more applications being accepted  Awaiting Funding Decision/Possible External Funding

About the Project

We are seeking applicants for the following PhD opportunity. The successful applicant will join a student cohort in Environment, Biodiversity and Genomics, training together, following an exciting programme designed to inspire the next generation of environmental experts, managers and leaders. They will be equipped to address some of the toughest challenges of our time. 

Research environment

The School of Biological and Behavioural Sciences (SBBS) 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 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. This work would be done in collaboration with the Rakyan laboratory, a leading group in epigenetic inheritance and nanopore-based methylation detection. Both groups are part of the QMUL Epigenetics Hub, a highly dynamic network of laboratories with a wide range of expertise in epigenomics.

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, Nanopore sequencing and methylation calling, transposable element annotation) 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. 

Project description

Coral reefs are one of the most biodiverse ecosystems on the planet. Corals can live in nutrient poor waters thanks to their symbiotic relationship with dinoflagellates, a group of unicellular algae that feed their cnidarian hosts via photosynthesis. The symbiosis can be disrupted by increasing sea water temperatures, causing the coral to expel the dinoflagellate. Most interestingly, dinoflagellates have unique genome architectures. Dinoflagellate genomes can be gigantic (>200 Gb) and have almost undetectable levels of histones, the core chromatin proteins of any other eukaryotic lineage. Similarly, coral symbiotic dinoflagellates of the Symbiodiniaceae family have unique DNA methylation patterns among eukaryotes. In previous work, we found that widespread methylation on CG dinucleotides coexisted with very localised CH (where H is C,A,T) methylation on transposable elements. However, the very repetitive nature of dinoflagellate genomes precluded a glimpse on the epigenetic patterns found within the abundant long transposable elements in these species.

To overcome this limitation, this project will use Nanopore long read sequencing to detect modified cytosines in Symbiodiniaceae species. Bisulfite treatment (the current gold standard to study DNA methylation) breaks DNA and can compromise read mappability, in contrast, long reads can be reliably mapped to unique transposable elements and do not depend on harsh DNA treatment. Furthermore, dinoflagellates are known for having abundant hydroxymethyl-uracil base in their genome, a rare base which is in principle detectable using Nanopore sequencing training neural networks. Since transposable elements are among the top differentially expressed genes in symbiotic versus free-living Symbiodinium cells, this indicates that epigenetic regulation of transposable elements by DNA modifications might offer key molecular insights governing symbiosis with the coral host.

Eligibility and applying

Applicants must:

  • Be Chinese students with a strong academic background.
  • Students must hold a PR Chinese passport.
  • Applicants can either be resident in China at the time of application or studying overseas. 
  • Students with prior experience of studying overseas (including in the UK) are eligible to apply. Chinese QMUL graduates/Masters’ students are therefore eligible for the scheme.

Please refer to the CSC website 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, including molecular biology, bioinformatics, plant biology or genomics. A masters degree is desirable. In a multidisciplinary project like this, candidates are unlikely to have a background in all disciplines involved, yet previous in experience in one would be beneficial (i.e. Bioinformatics, Molecular biology, Cell biology).

Applicants are required to provide evidence of their English language ability. Please see our English language requirements page for details.

The deadline for applications to Queen Mary is 30th January 2022. Applicants will need to complete an online application form by this date 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 CSC 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 CSC for the scholarship by the advertised deadline with the support of the project supervisor. For September 2022 entry, applicants must complete the CSC application on the CSC website between 10th March - 31st March 2022.

Only applicants who are successful in their application to CSC can be issued an unconditional offer and enrol on our PhD programme

Apply Online


Funding Notes

This studentship is open to students applying for China Scholarship Council funding. Queen Mary University of London has partnered with the China Scholarship Council (CSC) to offer a joint scholarship programme to enable Chinese students to study for a PhD programme at Queen Mary. Under the scheme, Queen Mary will provide scholarships to cover all tuition fees, whilst the CSC will provide living expenses for 4 years and one return flight ticket to successful applicants.

References

Host labs:
1. Recurrent acquisition of cytosine methyltransferases into eukaryotic retrotransposons. de Mendoza A, Bonnet A, Vargas-Landin DB, Ji N, Hong F, Yang F, Li L, Hori K, Pflueger J, Buckberry S, Ohta H, Rosic N, Lesage P, Lin S, Lister R. Nature Communications. 9(1):1341. 2018.
2. The Epiallelic Nature of Mouse rDNA. Fran Rodriguez-Algarra, Amy Danson, Rob Seaborne, Selin Ylidizoglu, Haru Yoshikawa, Pui Law, Zak Ahmad, Victoria Maudsley, Ama Brew, Nadine Holmes, Alan Hodgkinson, Sarah Marzi, Pradeepa Madapura, Matthew W Loose, Michelle Holland, Vardhman Rakyan. BioRxiv. (2021).
Other relevant publications:
3. Comparison of 15 dinoflagellate genomes reveals extensive sequence and structural divergence in family Symbiodiniaceae and genus Symbiodinium.
González-Pech, R.A., Stephens, T.G., Chen, Y. et al.. BMC Biol 19, 73 (2021)
4. DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation.
Liu, Y., Rosikiewicz, W., Pan, Z. et al. Genome Biol 22, 295 (2021)
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