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EASTBIO On the origin of environmental RNA interference: multicopy gene families silenced in nematodes


School of Biological Sciences

Dr C Abreu-Goodger , Dr A Buck Wednesday, January 06, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

RNA molecules can be secreted by cells into their environment, move between cells, and even between different organisms, potentially encoding “messages” that can be understood by the receiver. A lot of research is still needed to describe the mechanisms of RNA communication, and to understand the functional and evolutionary aspects of this transfer of genetic information.
While studying the genomic origin of small RNAs in Heligmosomoides bakeri, we realised that this parasitic nematode has an increased tendency to silence multicopy protein-coding gene families using small RNAs, compared to the free-living Caenorhabditis elegans. The H. bakeri genome also encodes a large number of transposable elements, many with hundreds or thousands of copies, which appear to be similarly silenced. This suggests a mechanistic hypothesis: the appearance of multicopy gene families triggers the RNA interference machinery to produce small RNAs to silence detrimental copies. Our results also suggest that small RNAs derived from multicopy gene families could be particularly well suited for environmental interactions with other organisms. Perhaps sequence divergence between gene copies is then advantageous for producing novel small RNA with higher sequence divergence, that can interact successfully with target RNAs inside another organism.
We would now like to understand if our observations in H. bakeri hold in other parasitic nematodes, and if we can use this to shed light on the origin of environmental RNA interference. We ask the following questions:
• Are small RNAs produced from multicopy gene families in other nematodes, and is this associated to lifestyle?
• Regarding the evolution of silencing multicopy gene families: Are recent gene expansions targeted more frequently? Do newer copies become targeted while the ancestral copy is protected in some way?
• Beyond the number of copies, is there a functional distinction between gene families that are targeted and those that are not?
• Can the gene families targeted by small RNAs help increase the diversity of the secreted small RNA sequence space?
This project is mainly bioinformatic and is part of an ongoing collaboration between Amy Buck (small RNA biochemistry), Amy Pedersen (ecology of host-parasite interactions), Darren Obbard (population genetics) and Cei Abreu-Goodger (small RNA bioinformatics). The student can also propose new directions, taking advantage of our combined expertise.
The 3-year timetable:
• Year 1: Training in bioinformatics and reviewing the literature of RNA silencing and evolution of gene families. Developing skills including genome annotation, comparative genomics, functional annotation of gene families, phylogenetics, prediction of transposable elements, analysis of high-throughput sequencing data.
• Year 2: Producing consistent annotation of the nematode genomes that will be compared. Analysing small RNA sequencing data to infer the most interesting gene families in different species. Inferring the evolutionary relationships within gene families from which small RNAs are derived. Quantifying small RNA production from each copy of each gene family.
• Year 3: Performing computer simulations to measure the expected sequence divergence of small RNAs derived from different gene families. Integrating results to evaluate hypotheses regarding the evolution of gene families and the production of small RNAs for communication between species.

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How to Apply:
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Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership View Website
This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition fees. The fee difference will be covered by the University of Edinburgh for successful international applicants. Please refer to UKRI website View Website and Annex B of the UKRI Training Grant Terms and Conditions
View Website for full eligibility criteria.



References

• Bermúdez-Barrientos JR, Ramírez-Sánchez O, Chow FW, Buck AH, Abreu-Goodger C. Disentangling sRNA-Seq data to study RNA communication between species. Nucleic Acids Res. 2020 Feb 28;48(4):e21. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31879784/
• Chow FW, Koutsovoulos G, Ovando-Vázquez C, Neophytou K, Bermúdez-Barrientos JR, Laetsch DR, Robertson E, Kumar S, Claycomb JM, Blaxter M, Abreu-Goodger C, Buck AH. Secretion of an Argonaute protein by a parasitic nematode and the evolution of its siRNA guides. Nucleic Acids Res. 2019 Apr 23;47(7):3594-3606. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30820541/
• Buck AH, Coakley G, Simbari F, McSorley HJ, Quintana JF, Le Bihan T, Kumar S, Abreu-Goodger C, Lear M, Harcus Y, Ceroni A, Babayan SA, Blaxter M, Ivens A, Maizels RM. Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat Commun. 2014 Nov 25;5:5488. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25421927/

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