This project is in competition for funding from the NERC Great Western Four+ Doctoral Training Partnership (GW4+ DTP) for entry in October 2023. The GW4+ DTP consists of the Universities of Bath, Bristol and Exeter and Cardiff University plus five prestigious Research Organisation partners: British Antarctic Survey, British Geological Survey, Centre for Ecology & Hydrology, the Natural History Museum and Plymouth Marine Laboratory.
Lead Supervisor: Stefan Bagby, University of Bath, Department of Life Sciences
Co-Supervisors: Ronald Jenner, Natural History Museum; Rhys Farrer, University of Exeter
Centipede venoms are complex proteinaceous cocktails used for both predation and defence. Recent research has shown that complex venoms have evolved in parallel in the major centipede lineages from a relatively simple ancestral venom that existed more than 430 million years ago. Uniquely among venomous animals, horizontal gene transfer (HGT) has played a major role in stocking centipede venom arsenals, involving recruitment of at least five gene families from bacterial and fungal donors across at least eight HGT events. Three of the gene families recruited by HGT are virulence factors in bacterial donor taxa. Centipedes have therefore repurposed bacterial weapons as venom components. Unpublished data from co-supervisor Ronald Jenner and colleagues, moreover, show that HGT has also contributed to the evolution of the defensive secretion that lithobiomorph centipedes produce and deliver with their terminal pair of legs. Interestingly, these data also show that bacteria exist in parts of these defensive leg glands, raising the possibility that these bacteria contribute to the production of defensive toxins.
Important uncertainties remain about the precise contribution of HGT to the evolution of chemical weapons in centipedes, and about the involvement of bacteria and fungi in chemical weapons production. These uncertainties arise mainly from the lack of centipede microbiome studies and the availability, until very recently, of only one publicly available centipede genome sequence. Three recent centipede genome sequences mean that four of the five main centipede lineages have genomic representation. In this project, we will exploit the recent expansion in genomic resources, together with data that we generate during the project, to shed new light on the evolution of the chemical weapons of centipedes.
Project Aims and Methods
We will define the roles played by HGT from bacteria and fungi in the production and evolution of chemical weapons in centipedes, and examine whether bacteria and fungi contribute directly to these secretions. This will be achieved using several complementary approaches. Published genome data will be combined with genome sequences that we generate, using nanopore technology, to detail how and where venom and defensive centipede toxins arose via HGT from microbes, and to provide new insights from resolution of multiple features such as structural variants of toxin genes, repetitive sequences, gene/region duplications, and cytosine methylation, as well as from phylogenetics studies. Alongside genome sequencing, nanopore sequencing of venom and defensive gland transcriptomes of previously studied and new centipede species will furnish insights into expression patterns and novel venom toxin isoforms. Together with phylogenetic analyses of toxin families, this programme of research will elucidate the contribution of HGT and microbial symbionts to the chemical weapons of centipedes, and improve our understanding of the complex phylogenetic histories of horizontally transferred venom components.
To investigate why HGT has made such an exceptional contribution to the chemical weapons of centipedes, we will combine nanopore and Illumina sequencing to profile centipede microbiomes, including those of the venom system, defensive legs, and eggs/reproductive organs.
We will also generate the first insights into the bioactivities and functions of the venom components that were recruited via HGT. Functional data exist for very few centipede venom toxins, and none for those recruited via HGT. For example, two of the horizontally transferred bacterial virulence factors in centipede venoms function as pore-forming toxins in bacteria. Since the centipede homologues have retained the relevant domains, assays could test whether they have retained pore-forming activity and function as cytotoxins. Other potential assays include enzyme and neurotoxin assays, as enzymes and neurotoxins are common centipede venom components.
This multi-approach plan allows for substantial flexibility and skill development for the student, and maximises the potential for making important and detailed discoveries.
Laboratory-based skills are desirable. Experience with analysis of genome and/or transcriptome sequence data, as well as with phylogenetic and comparative analyses, would be useful. Training will be provided for both laboratory and bioinformatic analyses.
Applicants must have, or expect to receive, a UK Honours degree 1st or 2.1, or international equivalent.
Non-UK applicants must meet the programme’s English language requirement by 01 February 2023 (unless you will be awarded a UK degree or degree conducted in English before your PhD start date).
This project involves collaboration between two top 20 UK universities, a world class museum, and an innovative, forward thinking and successful technology company. The student will have the chance to work in all four organisations, including a minimum three-month placement at Oxford Nanopore.
The student will be trained in nanopore sequencing and bioinformatics. There is potential for fieldwork: for example, one target could be to provide the first genome sequence of a species in the fifth major centipede lineage - this would require sample collection in Tasmania or New Zealand.
Enquiries and Applications:
Informal enquiries to Dr Stefan Bagby - [Email Address Removed]
Formal applications should be made via the University of Bath's application form for a PhD in Biochemistry
Identify your application as for NERC GW4+ DTP competition in Section 3 Finance (question 2). Quote project title and supervisor’s name in ‘Your research interests’.
More information about applying for PhD at Bath on our website.
We welcome and encourage student applications from under-represented groups. We value a diverse research environment. If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.
Project keywords: biochemistry, bioinformatics, evolution, genomics, microbiology