Genetic analysis of arbovirus transmission by insect vectors

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

Culicoides biting midges spread a number of viruses that cause severe disease in animals, including bluetongue in ruminants, and possibly the recently emerged Schmallenberg virus. Sequencing of the Culicoides sonorensis genome has been now initiated at IAH, in collaboration with TGAC and EBI, to decipher the molecular basis of Culicoides phenotypic variation. This opens up new areas of globally significant vector-biology research, including molecular studies of vector-pathogen-host interactions, to define genetic ‘drivers’ of vector competence and transmission. Genomic DNA (and RNA) from C. sonorensis colonies at IAH and the C. sonorensis ‘KC’ cell line, is being assessed using the Illumina HiSeq2000 sequencing platform. Our collaborators at EBI will provide the first annotated genome for any Culicoides spp., that together with insects from the IAH colonies, will allow us to investigate genetic factors and molecular processes involved in orbivirus transmission, replication and vector competence.
Analyses of genome-wide SNPs in multiple Culicoides spp and colony-insects bred for different traits will elucidate arthropod phylogenetic relationships and explore the underlying genetics of arthropod blood-feeding and immunology. Phenotypic differences within the colony at IAH, including sensitivity and permissive or non-permissive characteristics for virus infection/replication, will be related to genotype using current mapping strategies for identifying genetic loci involved in vector competence.
 
Title Culicoides animations 
Description This project was funded by a BBSRC responsive mode grant and was initiated on 1st February 2013. Culicoides biting midges inflict substantial economic damage on global livestock production and trade by acting as vectors of arboviral pathogens. The hypothesis that our project addresses is that genetic variation within species influences the vector competence of Culicoides for BTV strains and hence impacts upon the epidemiology of this virus worldwide. The primary deliverable of this project is the elucidation of the genetic basis of vector competence of C. sonorensis for bluetongue virus (BTV). It will also generate the first accurately annotated genome of a Culicoides species worldwide opening up vast opportunities for comparative genomics. This will provide fundamental insights into arbovirus: Culicoides systems that to date remain poorly characterised. The genome sequence will underpin advances in improving food security by protecting UK agriculture from potentially catastrophic exotic animal diseases. There is significant potential for this research to facilitate the development of new control strategies for these important animal diseases, with consequences for agricultural practice and food security, both in the UK and worldwide. While the primary focus of the project is academic, a range of different groups will additionally benefit from the results, and we have formulated plans to engage them in the project. One of the principal approaches for the dissemination of the outputs for this project has been the production of animated videos funded by the "Excellence with Impact" competition. This novel approach of using animations to describe our work to a general audience goes above and beyond the intended scientific audience of the project. This has also been of interest to the Animal Health Industry who will benefit through the production by engaging with the public. The animations have also been used in outreach activities to ensure that Farmers and Veterinarians benefit from the project, by gaining a deeper understanding of Culicoides and the pathogens they transmit. The high profile nature of the incursion of recent BTV-8 incursions has facilitated an opportunity to provide background information to farmers and veterinarians on what was until recently viewed as exotic pathogens of little relevance to the UK. We intend to build on this advance by further engagement across the veterinary and farming stakeholders, by detailing significant findings made during the project and how we intend to turn research into practice. Finally, we will engage with the Schools who will have an interest in both the advanced nature of the techniques involved in the study (STEM) and the high profile of Culicoides as an insect vector group in the UK. We will exploit this unique opportunity through the animated videos to both promote the objectives of BBSRC and explore this area of science in an understandable fashion. Scientists employed during the project are encouraged to take part in public engagement. In addition, the entomology group has wide experience of outreach activities through a variety of events run primarily with the Royal Entomological Society and the animated videos will also be utilised for this engagement. Exhibit materials, including the animated videos, will be used in further outreach and in open days for The Pirbright Institute, TGAC and EBI. Finally, our laboratory is already involved in STEM (Science, Technology, Engineering and Mathematics) activities for schools. Dr Fife is an active STEM ambassador, which creates opportunities to inspire young people and develop their creativity, problem-solving and employability skills the UK's future competitiveness. All researchers will be encouraged to participate in STEM activities including school visits and career days. 
Type Of Art Film/Video/Animation 
Year Produced 2015 
Impact This has been selected for the final of the BBSRC Excellence with Impact awards. 
 
Description Research on this project resulted in funding of Genetic mapping of vector competence in Culicoides sonorensis and additional collaborations and grants.
Exploitation Route This grant has successfully produced the first ever genome sequence of the disease insect vector of the Culicoides genus.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://www.pirbright.ac.uk/research/GeneticsGenomics/Default.aspx
 
Description Research on this project resulted in funding of a grant involving Genetic mapping of vector competence in Culicoides sonorensis.
First Year Of Impact 2012
Sector Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Contributed to Chief Medical Officers report- Genomics section
Geographic Reach Europe 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
URL https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/6310...
 
Title Culicoides genome sequence 
Description The preliminary data for the Culicoides genome sequencing is already proving to be of great interest to a number of groups and people, both within the Institute and beyond. 
Type Of Material Technology assay or reagent 
Year Produced 2014 
Provided To Others? Yes  
Impact The preliminary data for the Culicoides genome sequencing is already proving to be of great interest to a number of groups and people, both within the Institute and beyond. 
 
Description EBI Culicoides genome project 
Organisation EMBL European Bioinformatics Institute (EMBL - EBI)
Country United Kingdom 
Sector Academic/University 
PI Contribution Performed experiments and provided material for Sequencing and genome build of the Culicoides genome project
Collaborator Contribution Sequencing and genome build for Culicoides genome project.
Impact Publication and public release of genome data for Culicoides genome project
Start Year 2013
 
Description Genetic mapping of vector competence in Culicoides sonorensis. 
Organisation EMBL European Bioinformatics Institute (EMBL - EBI)
Country United Kingdom 
Sector Academic/University 
PI Contribution The primary deliverable of this project will be the elucidation of the genetic basis of vector competence of C. sonorensis for bluetongue virus (BTV) and African horse sickness virus (AHSV). It will also generate the first accurately annotated genome of a Culicoides species worldwide.
Start Year 2012
 
Description USDA Culicoides 
Organisation U.S. Department of Agriculture USDA
Department National Animal Disease Center
Country United States 
Sector Public 
PI Contribution Combined data for Culicoides genome project to enable publication in high impact journal.
Collaborator Contribution Transcriptomics data for vector competence analysis and genome build.
Impact Combined data for Culicoides genome project to enable publication in high impact journal.
Start Year 2014
 
Description Chair of organising Committee for Wellcome Trust-Animal Genetics and Diseases 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This meeting brought together specialists working on the interface between genomics, genetic engineering and infectious disease with the aims of improving animal and human health and welfare.

Scientific sessions included:
Genetics of immune responses and disease resistance
Genetically engineered livestock (including genome editing)
Quantitative genetics and epigenetics applied to disease
Epidemiology and pathogen evolution
Bioinformatics, comparative and functional genomics
Precision medicine of animal companions
Year(s) Of Engagement Activity 2017
URL https://coursesandconferences.wellcomegenomecampus.org/events/item.aspx?e=635&dm_i=2SUU,HOGH,4R4AW1,...
 
Description Holt School Surrey. Bee meadow & A-level outreach Talk. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I discussed the importance of pollinators for biodiversity and food security with the younger students. I also discussed careers in science with A-Level students. There was good interaction and many questions surrounding both topics.
Year(s) Of Engagement Activity 2018
 
Description Innovate Guildford Outreach (12th March) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact With amazing exhibits, activities, workshops, talks and competitions, it's FREE to attend. Explore the four zones: Engineering, One Health, Digital Media and Future Living, experience interactive performances, hear inspiring speakers (including leading gaming pioneer Peter Molyneux and animal health pioneer Professor Nick Bacon) and take in an amazing atmosphere. Theatre, music and comedy will feature through the day, with everything from how technology might have affected Shakespeare's plays to risky recycling and photographic secrets.
Year(s) Of Engagement Activity 2017
URL https://www.guildford.gov.uk/innovateguildford
 
Description Kingdown School Warminster Wiltshire talk to 6th form students about career in science. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I presented my career path to the students to engage them on STEM careers. I had a good level of discussion and many questions.
Year(s) Of Engagement Activity 2018
 
Description MF STEM1 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 'What's My Job?' careers education session on being a BBSRC research scientist. Well received and good interaction.
Year(s) Of Engagement Activity 2015
 
Description MF STEM2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 1200 students from Years 9-13 i.e. pre- and in sixth form. Our exhibits included Vero cells in flasks, plaques, Vero cells viewed down a microscope, 2D real-size models of sequencing kit, virus and DNA models, careers hand-outs.
Year(s) Of Engagement Activity 2015
 
Description MF STEM3 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Students from Years 5-6 i. Gave a talk on the Ebola virus outbreak in west Africa. Porvided virus and DNA models, careers hand-outs.
Year(s) Of Engagement Activity 2016
 
Description Tillingbourne bug hunt. New Rd, Chilworth, Guildford GU4 8NB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Stimulating increased interest in science and research. Good interest and engagement.
Year(s) Of Engagement Activity 2018
 
Description Winston Churchill Careers Fair. Winston Churchill School, Hermitage Road, St Johns, Woking, Surrey, GU21 8TL 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact AS attended and presented at this event to stimulate increased interest in science and research.
Year(s) Of Engagement Activity 2018