Surveying blood-borne, tissue and gut-dwelling parasites of UK wildlife using metagenomics: unlocking genomic novelties in search of parasite control strategies of the future

Estimates suggest that up to half of all known animal and plant species on Earth are parasitic at some stage of their lifecycle, and that almost all animal and plant species may be host to a parasite.  Understanding the diversity and evolution of parasitism is critical for understanding ecosystems, emergence of zoonoses or infection of new species.  Greater knowledge of the genomic diversity of parasites can reveal genomic novelties that unlock new insights or can be targeted by approaches for parasitic disease control.  However, though some major parasites causing significant disease, or model-system parasites for research, are well studied, many other parasites and their lifecycles or hosts remain poorly described or unknown.

The Darwin Tree of Life project aims to sequence the genomes of all 60,000 known eukaryotic species in Britain and Ireland.  This project is part of a larger global initiative, known as the Earth BioGenome Project, aiming to sequencing all complex life on Earth.   However, whilst non-parasitic organisms of terrestrial and aquatic environments may perhaps be observed for study with relative ease, parasites, in occupying a third environment – the host – are often not simple to collect or isolate from their host environment tissues, and study.  Hence, many parasites remain poorly studied or undiscovered.  A move is underway to include collections of major parasite species but the size of the task is immense and much remains to be understood about their prevalence, host ranges and ecology.

In this project the student will use a metagenomic approach to survey UK wildlife for blood-borne, tissue and gut parasites. Collaborators at the Wellcome Sanger Institute have recently demonstrated that draft genomes of protozoan parasites can be assembled after directly sequencing whole blood from an infected mammal (Aunin et al., 2020).  We will therefore generate draft genome assemblies from the metagenome data and use it to identify species that might be targeted for isolation and extensive sequencing to produce reference genomes as part of the Darwin Tree of Life project.

The project will involve UK-based field work, and will involve identifications and dissections of non-protected wild-caught hosts of parasites as appropriate. Specific sample preparation and storage protocols will be observed as per requirements of the Darwin Tree of Life project. Basic molecular biology and bioinformatics methods will be employed to identify hosts and parasites. Additional DNA extractions and sequencing will take place at Sanger, producing data that the student will use to assemble genome sequences. A range of bioinformatic techniques will then be applied to the data, assisted by Sanger supervisors. An opportunity to visit the Sanger hub of the Darwin Tree of Life project may be possible, dependent upon covid19 restrictions at the time.

For further information on the Darwin Tree of Life project visit the following links;

https://www.sanger.ac.uk/programme/tree-of-life/

https://twitter.com/sangertol

https://www.darwintreeoflife.org/

https://twitter.com/darwintreelife

https://www.sanger.ac.uk/group/berriman-group/

This proposed project aims to:

1. Collect blood, urine, faecal and tissue samples from UK wildlife, as appropriate to host species, and identify parasitic species therein using DNA barcoding

2. Assemble draft genome sequences across a taxonomic range of blood-borne, tissue and gut-dwelling parasite species,

3. Undertake comparative genomic analyses led by the data collected to:  i) provide basic understanding of parasite diversity in surveyed wildlife,  ii) uncover features of previously undescribed genomes,  iii) provide novel candidate nucleic-acid-based blood-borne, tissue and gut markers of infection and pathogenesis in potentially model system species for future diagnostic research.

Where does the project lie on the Translational Pathway?

T1 (Basic Research) – T2 (Human/Clinical Research)

Expected Outputs

After the completion of this PhD project (3-year period), this project would;

 

  1. Provide genome sequences for use by the wider scientific community,
  2. Provide essential data for the Darwin Tree of Life project on parasite diversity in UK wildlife and targets for reference genome sequencing, as well as extensive lists of candidate sequences available from various host tissue samples,
  3. Provide tested protocols for metagenomic sequencing of parasites from a range of host tissue samples,
  4. Result in multiple publications in leading peer-reviewed, open access journals

 

Training Opportunities

LSTM provides a unique programme of training opportunities, events and seminars (updated each semester) to encourage students to meet other researchers from a wide range of fieldwork, statistical, bioinformatics, and laboratory specialities to grow their network.  LSTM utilises innovative Technology Enhanced Learning initiatives to ensure that students working in the field are able to interact as fully as possible with training sessions.  The full catalogue of MSc modules delivered at LSTM are available for study and students can attend lectures and seminars.

 

The student will receive the following training: 1. Animal sampling strategies: sampling and statistical data handling skills and methods designed for disease surveillance, trap sampling methods and animal processing (snails, arthropods and small vertebrates) 2. Necropsy of confirmed and suspected vertebrate hosts of parasites, 3. Pathogen isolation and processing in a biosecurity level 2 laboratory and 4. Parasite diagnosis,  4. Molecular biology methods and preparation of samples for basic and modern sequencing technologies,  5. Bioinformatics skills from basic sequence analyses to advanced computational and statistical handling of output data from modern sequencing technologies.

 

Skills Required

The potential candidate would require a high-quality degree in Life Sciences (Biology, Veterinary, or Medicine), basic knowledge on molecular biology and parasitology, and have good communication skills in English.  Previous experience in computing or bioinformatics is desired but not essential as full training will be provided.  The PhD candidate is expected to be highly motivated.

 

Key Publications associated with this project

Aunin E, Böhme U, Sanderson T, Simons ND, Goldberg TL, Ting N, Chapman CA, Newbold CI, Berriman M, Reid AJ. Genomic and transcriptomic evidence for descent from Plasmodium and loss of blood schizogony in Hepatocystis parasites from naturally infected red colobus monkeys. PLoS Pathog. 2020 Aug 3;16(8):e1008717. doi: 10.1371/journal.ppat.1008717. Epub ahead of print. PMID: 32745123.

International Helminth Genomes Consortium. Comparative genomics of the major parasitic worms. Nat Genet. 2018 Nov 5. doi: 10.1038/s41588-018-0262-1.

PubMed PMID: 30397333.

Lewin HA, Robinson GE, Kress WJ, Baker WJ, Coddington J, Crandall KA, Durbin R, Edwards SV, Forest F, Gilbert MTP, Goldstein MM, Grigoriev IV, Hackett KJ, Haussler D, Jarvis ED, Johnson WE, Patrinos A, Richards S, Castilla-Rubio JC, van Sluys MA, Soltis PS, Xu X, Yang H, Zhang G. Earth BioGenome Project: Sequencing life for the future of life. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4325-4333. doi: 10.1073/pnas.1720115115. PMID: 29686065; PMCID: PMC5924910.

Cwiklinski K, Allen K, LaCourse J, Williams DJ, Paterson S, Hodgkinson JE. (2015). Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach. Infect Genet Evol. 32:298-304.

Cwiklinski K, Dalton JP, Dufresne PJ, LaCourse J, Williams DJ, Hodgkinson J, Paterson S. (2015). The Fasciola hepatica genome: gene duplication and polymorphism reveals adaptation to the host environment and the capacity for rapid evolution. Genome Biol. 16:71.

Deadline: Thursday 11th February 2021; 12:00 noon GMT

Further details on the MRC/DTP and CASE programmes and application guidance and process can be found here