The BUG consortium Building Upon the Genome: using H. contortus genomic resources to develop novel interventions to control endemic GI parasites

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

Most food-producing animals are infected with a variety of different roundworms, or nematodes, many of which live in the digestive tract. These parasites cause a range of disease in their hosts, from diarrhoea and anaemia, to death, in severe cases. They are a major welfare issue and cause significant economic losses to farmers, in terms of reduced production and treatment. It is estimated that these worms cost the UK sheep industry a conservative £84 million per annum. At the present time these parasites are controlled using drugs known as anthelmintics, but many of these chemicals no longer work effectively because the parasites have developed resistance to them, analogous to antibiotic resistance in bacteria. How anthelmintic resistance arises and spreads throughout the worms on a farm is not known. The problem has become so serious in the UK that some sheep-farming enterprises have had to close because the worms can no longer be controlled. Our project will investigate ways of ensuring that the existing drugs are managed to minimise the occurrence and spread of resistance and will also study novel approaches to vaccine development. The current methods for detecting resistant parasites are labour intensive and insensitive, making early detection impossible and analysis of the extent of the problem difficult. This makes it hard to evaluate strategies aimed at reducing the spread of resistance. We need to develop more sensitive methods to detect resistant parasites and so must understand the genetic changes in the parasites that lead to resistance. We have recently sequenced the genome of one of these parasites called Haemonchus contortus (the Barber's pole worm) and found it to be large and complex, containing a similar number of genes to the human genome. Studying this genome will identify novel ways of controlling nematode infections and our research is aimed at using new technologies to ensure that farmers can continue to produce livestock effectively. We planto use information from the genome to identify markers of drug resistance in Haemonchus and in a closely related worm called Teladorsagia circumcincta, which is the most prevalent parasite found in the UK sheep population. By identifying the genetic changes in worms exposed to anthelmintics, we aim to understand how resistance arises and to develop markers to identify resistant worms on sheep farms. This information will be used to help model how resistance spreads and to investigate how different treatment schedules affect the development of resistance, taking into account climate change scenarios. In the longer term, we would like to develop vaccines against these worms. Although many attempts have been made to do this, most have not been successful, as we have no way of assessing whether the antigens tested to date are the most effective at stimulating a host immune response. However, our project will provide the basis for identifying genes that are under selection by the sheep immune system and therefore likely to be antigenic. We will combine results from this study with knowledge of where and when specific antigens are expressed in the worm to optimise the selection of potential vaccine candidates. Finally, the results from this project will be used to design sustainable control strategies for sheep parasites in the face of anthelmintic resistance and climate change. We have robust plans to engage with the farming community through workshops and publications to ensure that the implications of our work are translated into good farming practice. While this project focuses on parasites of sheep, we anticipate that much of what we learn about anthelmintic resistance will be directly applicable to parasites of cows, horses and pigs where anthelmintic resistance is an emerging problem. Moreover, as the same drugs are increasingly used to control related worms in humans, our work will also impact on human health.

Technical Summary

The aim of this project is to provide sustainable control of nematode parasites of sheep based on an improved understanding of AR and the identification of novel vaccine candidates. Nematodes from two sources will be sequenced: H. contortus from a genetic backcross between IVM-sensitive and resistant lines and T. circumcincta and H. contortus from farms with current clinical AR problems. We will use a method of genotyping by sequencing (ddRAD-Seq) that can be applied to large numbers of individuals, and whole genome sequencing of pools of larvae. This population genetics approach will be underpinned by significant improvements in the genomes of both nematodes based upon the construction of a genetic map for H. contortus and high coverage, individual worm sequencing for T. circumcincta. Markers of AR will be validated in a UK-wide bio-bank containing both parasite species, collected from farms with known histories of anthelmintic usage over several years. Analysis of AR-conferring regions of the genome will reveal the underlying mechanisms, which will be tested in a C. elegans transgenic model system. Once identified, AR markers will be used to study the origin and spread of resistance alleles and to model and assess the effects of different anthelmintic regimes on the development of AR. Additional modelling studies will address the impact of climate change on worm survival and effective refugia and will seek to future-proof any new management strategies. Sequencing data will be employed in a population genomics approach to vaccine discovery with the aim of identifying novel candidate antigens for future development. The study will be underpinned by a cost-benefit analysis of new management strategies and a knowledge exchange module that will involve close liaison with the farming industry to identify the optimal means of implementing new strategies.

Planned Impact

The beneficiaries of this project include the farming community and their advisors, the pharmaceutical industry and the general public. Our project will identify markers of AR and will improve our understanding of the mechanisms and spread of resistance throughout populations. Although much of the knowledge produced will be fundamental, it has the potential to have significant impact in the UK and internationally where the problems of AR are even more acute. The sLoLa will support innovation in science by applying new technologies and generating novel tools for parasitic nematode research. The project will provide excellent training opportunities for the post-docs in genetic, genomic and quantitative approaches to complex biological problems. We will ensure interactions amongst the post-docs by hosting training periods in each Institute. The group at WTSI contribute to several courses and workshops and so have significant experience of training in genomics and next-generation sequence data analysis. Skills acquired during the course of the project will be applicable to many other organisms and will equip the PDRAs for future careers in academia, the bio-tech or pharmaceutical industries.

We will generate data that are of considerable interest to the pharmaceutical industry, some of whose drugs are now largely ineffectual in various parts of the world. Our work will generate tools to detect and monitor resistance, which will be used to improve strategies to mitigate the development of AR. By shedding new light on the mechanisms of resistance, the results will influence the design and use of future anthelmintics and may identify opportunities to restore efficacy to current drugs. Although much effort has been invested in developing a vaccine for H. contortus, most attempts to protect sheep using these antigens in recombinant format have failed. We currently have no way of determining whether the antigens tested to date are the most effective, as they were not selected based on their association with protection in the field. A population genomics approach allows the identification of antigens under selection by the host immune system. It will also identify genes whose products are essential for survival, information that could be exploited in other ways, such as the design of novel inhibitors.

This project has the potential to impact upon farming practices in the UK and elsewhere. Previous advice such as 'dose and move', appears to result in an increased selection for resistance, but is still widely used. The SCOPS (Sustainable Control Of Parasites of Sheep) initiative provides farmers and vets with valuable up-to-date information and guidelines for parasite control but we still lack a basic understanding of the mechanisms of AR on which to base this advice. The development of effective parasite control strategies would improve animal health and welfare, the quality and safety of British lamb and the economic viability of the UK sheep industry. We will engage with farmers and vets through publications in the farming press, attendance at agricultural meetings, veterinary CPD courses, and workshops to determine how findings from this project can be used to establish the best means to improve farm profitability and animal welfare in both the short and the long term. Worm control in dairy herds was recently estimated to cost the UK economy £281 million per annum and the impact of AR would significantly raise that figure. Thus our work has the potential to contribute to the economy by increasing the efficiency of livestock production and safeguarding the industry against an inevitable future challenge. By helping produce high quality meat with excellent standards of animal welfare we hope to influence the public perception of British farming. We have opportunities to interact with the public at events such as the Royal Highland Show and with school children through engagement activities, such as science clubs.

Publications

10 25 50
 
Description This is a multi-centre award with different partners undertaking different aspects of the project. The mid-term report for the whole project was assessed in July 2017 and favourably reviewed, releasing the final two years of funding. Since then there have been a few staff changes/movements. Prof Alistair Stott (SRUC) has retired and his role as PI assumed by Dr Catherine Milne. Both PI and post-doc from the University of Bristol have moved: Professor Morgan to Queen's University, Belfast and Dr Hannah Vineer to a Fellowship at the University of Liverpool.

At the Wellcome Sanger Institute (WSI) significant progress has been made on refining the Haemonchus contortus genome with the assembly now representing essentially entire chromosomes. This is a major achievement since the publication of the draft genome in 2013 and was made possible by the application of long-read sequencing technologies (PacBio), optical mapping and intensive manual curation. The assembly and annotation is publicly available on WormBase Parasite (https://parasite.wormbase.org/Haemonchus_contortus_prjeb506/Info/Index/), providing a significant genomic resource for a broad group of Clade V nematodes, which include parasitic species of major veterinary and medical importance. This resource removes some of the dependency on Caenorhabditis elegans as a reference for which parasite-specific traits are not relevant. The chromosome-scale assembly now allows insight into chromosome evolution amongst these species, and offers a robust scaffold for genome-wide analyses of important parasite traits such as anthelmintic resistance. A publication describing the assembly and annotation is in an advanced stage of preparation.
Concurrently, work is underway to sequence and assemble the genome of the closely related species, Teladorsagia circumcincta, which is the major gastrointestinal parasite of sheep in the UK. Work on this species has been particularly challenging, as it has a genome size approximately double that of H. contortus and has a complex and highly polymorphic genome. Sequence data has been generated from DNA libraries for both short and long read sequencing, as well as DNA for optical mapping, all prepared at the University of Glasgow. These data have been used to assemble a draft T. circumcincta genome at the WSI, but we hope to further improve this assembly over the remainder of the BUG project. We plan to take advantage of recent advances that allow the generation of long read sequencing libraries from very low (10s of ng) quantities of DNA to generate data from a single T. circumcincta individual, reducing polymorphism. We will also generate Hi-C (chromatin conformation capture) and attempt to produce a genetic map using single-sperm sequencing to generate long-range scaffolding information to close this assembly. For both parasites, to enable annotation, additional RNA sequencing is being carried out on samples prepared from defined life cycle stages using the long-read Iso-Seq method.

At the University of Edinburgh and the Moredun Research Institute (MRI), efforts initially concentrated on establishing a new genetic cross between an anthelmintic sensitive (MHco3) and a multi-drug resistant isolate (MHco18) of H. contortus and the preliminary characterisation of the F1 progeny. In Glasgow, DNA was isolated from a single MHco3 female and her F1 progeny for genotyping at the WSI and the construction of a genetic map. The genetic map is complete and sib-ship analysis confirmed the polyandrous nature of female H. contortus, with progeny sequenced from the single female worm originating from at least eight male worms. In addition, triploid progeny were also identified. A paper summarising this work is now published (Doyle et al., A Genome Resequencing-Based Genetic Map Reveals the Recombination Landscape of an Outbred Parasitic Nematode in the Presence of Polyploidy and Polyandry. Genome Biology and Evolution 10(2):396-409).

The F2 population were used to infect additional animals, which were then treated with one of three drugs. Genotyping of pools of L3 recovered pre- and post-treatment has allowed a bulk segregant analysis to be carried out. Different regions of the genome were shown to be under selection by each of the three drugs, confirming distinct modes of action. For benzimidazole and levamisole, one major and several minor regions under selection were identified. For ivermectin, a more complex signal of selection was observed, which may be indicative of several genes contributing to resistance. A large region on Chromosome V was identified and efforts are on-going to narrow down the region and confirm the genes involved. Significantly, a similar locus on Chromosome V was also identified in a recent analysis of two geographically distinct ivermectin-resistant lines, based on a pre-existing genetic cross but which has been completed for publication as part of the consortium's work (Doyle et al. 2019. Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus, BMC Genomics, in press).

At the University of Glasgow, transcriptomic analysis was also carried out using male and female worms from both parental isolates and the F2 generation of the cross, with and without IVM exposure. As expected there were many constitutive differences in gene expression in the parental samples (MHco3 versus MHco18). However, genes that were also differentially expressed in pairwise comparisons of the F2 generation of the cross with and without IVM exposure represent a high confidence set of genes associated with IVM resistance. Many of the differentially expressed genes had orthologues in C. elegans. To prioritise candidate genes in the genomic locus under IVM selection, the transcriptomic data was used to identify genes that also showed differential expression in IVM-resistant adults. These included a number of kinases and several genes involved in regulating neuronal/behavioural plasticity. The effects of mutation or over-expression of selected genes are now being studied in C. elegans to determine whether they do indeed play a role in IVM resistance.

In Edinburgh, Bristol and MRI, field samples of T. circumcincta were collected pre- and post-drug treatment from sheep farms in different regions of the UK. At Glasgow, the larvae were processed for genotyping using ddRAD-Seq and whole genome pooled sequence at WSI. The data arising from this part of the project are currently being analysed.
At the University of Edinburgh, the focus has been on studying the emergence and spread of benzimidazole resistance. A novel deep amplicon sequencing method based on the Illumina Mi-seq platform has been used to study the phylogenetics of benzimidazole resistance mutations in field samples of T. circumcincta collected from three UK sheep flocks, selected to represent different aspects of sheep management and approaches to parasite control. Different frequencies of benzimidazole resistance mutations were seen in T. circumcincta in the three UK sheep flocks. Benzimidazole resistance mutations had nearly reached genetic fixation in the three-year study flock, highlighting a need for more refined knowledge of the dynamics of single or multiple resistance haplotypes and how their frequency changes over time. Such information will allow testing of hypotheses with reference to the selection pressures that lead to differences in resistance allele frequencies between sampling dates and animal groups.

Work at MRI has also focused on benzimidazole resistance; pyrosequencing of ß-tubulin isotype 1 SNPs associated with BZ resistance was undertaken on individual larvae of the H. contortus isolates and different generations of the crosses: MHco3 females crossed with MHco18 males and MHco18 females crossed with MHco3 males to gain an improved understanding of genetic selection of BZ resistance using genotypic and phenotypic readouts (i.e. does mating between resistant male worms and susceptible female worms result in greater or lesser phenotypic resistance?). The results have shown that a heterozygote resistance genotype at both P167 and 200 of ß-tubulin isotype 1 appears to result in greater phenotypic expression of resistance in F1 generations compared to homozygote resistance at either position. In a partnership between Glasgow and MRI, we have obtained additional funding from the Natural Environment Research Council (NERC) for a CASE PhD project to follow up on the phenotypic consequences and genetic basis of resistance to ivermectin. In addition, we obtained a second studentship from the University of Glasgow to work on levamisole resistance. Both students started in October 2019
At the University of Glasgow, work is ongoing to use computer models to study the spread of anthelmintic resistance in sheep nematodes. By modelling the frequency of resistance alleles and their associated genotypes within the worm population as they change in response to treatment, it is possible to highlight patterns in the emergence of resistance. These patterns depend both on how resistance is encoded (one gene versus many), and on the treatment regimens implemented. Data collected by other members of the consortium can be fitted to the models and predict the treatment regimens (such as treatment frequency and use of refugia) that might prolong the effectiveness of anthelmintic drugs.

At the University of Bristol, models for the weather-dependent population dynamics of T. circumcincta and H. contortus have been validated and an extended model incorporating the development of anthelmintic resistant phenotypes, grazing (and refugia) management, and anthelmintic treatments is complete. The model's underlying simplified representation of the ivermectin-resistant genotype is consistent with recent output from WSI and the model complements the more complex representation of the genotype in the Glasgow model. Simulations representing combinations of anthelmintic treatment and grazing patterns suggest that weather and climate play an important role in the speed of development of anthelmintic resistance; the predicted increase in resistance allele frequency following treatment varied year to year and between climatic zones. The objectives of the project were disseminated to stakeholders, alongside a request for reports of poor drug efficacy on farms in the south-west in order to source relevant H. contortus field isolates. This was achieved through local meetings of sheep farmers (including the Sheep SW event) and engagement with local veterinary practices, APHA and AHDB. Potential format and utilisation of decision support tools planned within the project were discussed with representatives of SCOPS, AHDB, NFU and APHA. This engagement will continue to be actively developed as the predictive modelling platform is built and adapted to decision support by both Prof Morgan and Dr Vineer, in their new roles.

At the SRUC the third and fourth of a series of in-depth workshops to obtain information about worm control practices used by farmers and the obstacles to implementing current good practice were completed. The results highlight the need for clearly defined recommendations for more sustainable control and that complexity is one of the main challenges in communication of key messages. A prototype stochastic simulation model to estimate the financial effects of AR and its management has also been constructed and will be further developed using outputs from models developed by Prof Morgan, Dr Vineer and colleagues. Potential links with the modelling work being undertaken at the University of Glasgow have also been explored. This work has also stimulated significant discussion on our online project management site and clearly indicates that the social science aspect of the project is becoming well integrated with the 'hard' science.'

Five BUG Consortium progress meetings have now been held (two in Glasgow, one each in Liverpool, Edinburgh and Cambridge) and attended by all project partners and the Advisory panel. Regular updates are posted on the BUG Consortium website, blog and twitter accounts. The BUG website again attracted over 2000 views in 2018, around 26% of which came from the UK, ~23% from the USA with the others from a wide diversity of countries.
Exploitation Route The availability of the H. contortus genome assembled to chromosomal level is a very significant advance in the field and of great value to other scientists working on parasitic nematodes. Identification of the loci under selection by each of three drugs in use will be of great interest to the livestock research community, to those working on resistance in human helminths and potentially to pharmaceutical companies. We have the potential to identify molecular markers of anthelmintic resistance which would be of value for testing in the field and for determining the outcome of various production methods aimed at slowing the spread of resistance. The data coming from modelling aspects of the project will also be of relevance for understanding how best to achieve strategic control of parasitic nematodes. Finally the workshops and outreach by many members of the BUG consortium have allowed good contact and feedback from stakeholders and the relevant agricultural communities.
Sectors Agriculture, Food and Drink

URL https://bugconsortium.wordpress.com
 
Description Staff involved in the BUG Consortium have participated in wide range of workshops and stakeholder discussions as detailed in the submission. Many of these workshops are aimed at determining the views of stakeholders on the strategic management of parasites in sheep.
First Year Of Impact 2016
Sector Agriculture, Food and Drink
Impact Types Societal

 
Description An integrated approach to tackling drug resistance in livestock trypanosomes.
Amount £343,273 (GBP)
Funding ID BB/S000143/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2019 
End 12/2021
 
Description BBSRC KTN CASE Award
Amount £150,000 (GBP)
Funding ID BB/N50385X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description NERC CASE Award
Amount £105,000 (GBP)
Funding ID NE/R008183/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 10/2018 
End 09/2022
 
Description Supporting the National Action Plan for Antimicrobial Resistance (SNAP-AMR) in Tanzania
Amount £3,089,371 (GBP)
Funding ID MR/S004815/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 05/2018 
End 04/2021
 
Description University of Glasgow Scholarship
Amount £100,000 (GBP)
Organisation University of Glasgow 
Sector Academic/University
Country United Kingdom
Start 10/2018 
End 03/2022
 
Description iBAHCM internal funding
Amount £3,000 (GBP)
Organisation University of Glasgow 
Sector Academic/University
Country United Kingdom
Start 03/2017 
End 08/2017
 
Title Haemonchus contortus v2.0 genome assembly and annotation 
Description A greatly improved genome assembly and annotation for Haemonchus contortus, which now represents intact chromosomes for this nematode parasite: the first for one of the major groups of helminth parasites. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact The assembly has already underpinned research both from our group (publications listed in publication section) and upcoming research by a number of other research groups (e.g. Gilleard and Wasmuth groups, Calgary; Blaxter group, Edinburgh) 
URL https://parasite.wormbase.org/Haemonchus_contortus_prjeb506/Info/Index
 
Description 26th WAAVP_Chaudhry and Sargison 
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 Invited talks: Application of molecular methods and conventional parasitology to understand ovine nematode parasite co-infections, in the absence of intervention; Genomic and genetic approaches to identify loci linked to the anthelmintic resistance in Haemonchus contortus.
Year(s) Of Engagement Activity 2017
 
Description 9th International Sheep Veterinary Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentations and engagement by BUG researchers relating to the BUG project. Plenary talk: Improved small ruminant production efficiency through global solutions to local challenges and local solutions to global challenges. Keynote talk: Anthelmintic resistance and sustainable helminth control. Other talks: Comparison of nematode parasite diversity and co-infections between feral and commercially managed sheep; Building upon the Haemonchus genome; Identifying animal health priorities for livestock farmers in rural Malawi; Investigation of productivity in a southern Indian Malabari goat herd shows opportunities for planned animal health management to improve food security; Assessing seasonal changes in strongylid nematode biome structures in a wild sheep population; A twelve month study of faecal worm egg counts on three farms and the impact of modern management; An evaluation of UK sheep farmers attitudes and behaviours towards sustainable roundworm control; Patterns of faecal nematode egg shedding after treatment of sheep with a long-acting formulation of moxidectin;
Year(s) Of Engagement Activity 2017
 
Description Anthelmintics: from discovery to resistance 111 - Chaudhry 
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 Talk: Evidence for the genetic linkage of three microsatellite makers to an ivermectin resistance locus in the genetic crossing of Haemonchus contortus strains.
Year(s) Of Engagement Activity 2017
 
Description Anti-microbial resistance scoping meeting Bangalore, India 
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 workshop, held under the auspices of BIS, brought together researchers from India and the UK working on drug resistance in various organisms.
Year(s) Of Engagement Activity 2016
 
Description Blog on BUG consortium grant 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We curate a blog on the BUG project (https://bugconsortium.wordpress.com)
Year(s) Of Engagement Activity 2015,2016,2017
 
Description British Cattle Veterinary Association 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact BCVA youngstock course. Parasite control in youngstock at grass: gastrointestinal helminth infections and lungworm.
Year(s) Of Engagement Activity 2017
 
Description CEED/Anwar seminar at Royal Veterinary College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited presentation on anthelminthic genetics to audience of researchers and students at Royal Veterinary College, London
Year(s) Of Engagement Activity 2018
 
Description Conference presentation - Ecology, Evolution and Genomics of C. elegans and other Nematodes. Wellcome Sanger Institute, Cambridgeshire, UK. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference presentation - C. elegans and other nematodes, Hinxton
Year(s) Of Engagement Activity 2018
 
Description Dr Cath Milne ran a workshop on best practice in worm control, Stirling 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Workshop on worm control
Year(s) Of Engagement Activity 2018
 
Description Dr Cath Milne ran a workshop on best practices in worm control in Penrith 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Discussion forum on best practices for control of worms
Year(s) Of Engagement Activity 2018
 
Description Engagement in Pakistan 
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 Pleanry and invited talks at PARACON: Recent Advances and Emerging Issues in Parasitology. Lahore, Pakistan. 25th-26th October 2017: Global Challenges facing helminth control in small ruminants - lessons for other livestock species; Genomic and genetic approaches to identify loci linked to anthelmintic resistance; The BUG (Building Upon Genome): Genomic and genetic approaches to identify loci linked to the anthelmintic resistance in Haemonchus contortus. Engagement and outreach with undergraduate veterinary and post graduate students and academic and clinical staff at University of Veterinary and Animal Sciences, Lahore: Roundworm control in cattle: why do we need innovative research tools?; The need for improved global small ruminant production: challenges and solutions; Plenary and invited talks at University of Central Punjab: Genetic crossing work in the model parasitic nematode, Haemonchus contortus; Applications of next generation sequencing methods in parasitology research.
Year(s) Of Engagement Activity 2017
 
Description Exlana ram sale 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact A presentation was given by Dr Hannah Rose to sheep farmers and breeders attending the Exlana ram sales. Around 50 farmers attended. The talk focused on utilising predictive modelling to enhance breeding strategy for parasite resistance under climate change, and hence reduce reliance on anthelmintic drugs and slow drug resistance. Material arising from model development under the BUG project was presented. Discussion ensued and farmers reported increased appreciation of the possible changes in epidemiology under climate change, and how breeding strategy should take this into account.
Year(s) Of Engagement Activity 2016
 
Description Farm visits and resistance testing 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact As part of sampling within the project, 16 farms in SW England were visited to conduct faecal egg count reduction tests (FECRT), the main method of anthelmintic resistance detection on farms (Dr Hannah Rose, Ms Katie Bull and Dr Eric Morgan participated). Professional teams from the supporting veterinary practice were included in the tests, which supported training of 5 veterinary surgeons and 3 veterinary nurses in correct procedures, including marking, drenching and faecal sampling procedure, and sensitive faecal egg counting methods. The practice team is now capable of conducting FECRT properly and offers this service to clients.
Year(s) Of Engagement Activity 2016
 
Description Final year talk at sponsor AHDB Beef and Lamb's PhD conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact A 'final year' presentation was given about the research to a large group made up of industry workers of a sponsor, AHDB Beef and Lamb, with their dairy and pig partners and others working within the industry. In addition other PhD students of the sponsor and their supervisors were also present, representing many universities and organisations across the UK. Questions and discussions related to the research contined ad hoc over the two day conference, with the chance to also hear about other research in the farming industry and impacts/requirements for further research needed.
Year(s) Of Engagement Activity 2018
URL https://ahdb.org.uk/phd-studentships
 
Description Game playing at the Royal Highland Show 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact We made a game "Fishing for worms" to help educate the public about the issue of anthelmintic resistance
Year(s) Of Engagement Activity 2016
 
Description Invited Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An invited talk was presented by Dr Stephen Doyle at La Trobe University, Melbourne, Australia, entitled "Sex, drugs, and recombination in Haemonchus contortus"
Year(s) Of Engagement Activity 2017
 
Description Invited poster - Sheep Breeders Round table 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact The Sheep Breeders Roundtable is organised by one of the funding sponsors of the project, AHDB Beef and Lamb, and I was requested to take part. I provided two posters. One on species differences between strongyle populations at different sampling time points/groups of animals and a further poster, building on the first, but looking specifically at the determination of anthelmintic efficacy by faecal egg count reduction tests. I was able to attend the meeting and discuss the content of the posters and the wider project with those who attended. At the same time we were able to make an announcement about the wider BUG project, requesting material.
Year(s) Of Engagement Activity 2017
URL https://www.nationalsheep.org.uk/sbrt/
 
Description Invited presentation at Sheep Vet Society meeting, May 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I was asked to provide a 20 minute presentation on faecal egg counts, and the range of complicating factors affecting interpretation in practice. I provided an overview of various methods, discussing sensitivities of these and considered strongyle species population composition impact. In addition I looked at some of the more basic steps from collection to culture, which could impact on the number of eggs counted, and the species identified. There were between 50 and 100 vets present, with professionals involved in various other sheep enterprises (eg. breeding), industry etc present also. The talk stimulated discussion, and, at the autumn SVS meeting, further conversations surrounding the topic of faecal egg counting and anthelmintic resistance were had.
Year(s) Of Engagement Activity 2018
URL https://www.sheepvetsoc.org.uk/event/spring-meeting-may-2018
 
Description Invited seminar, Division of infectious diseases, University of Virginia School of Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar at University of Virginia, audience of professional researchers, students and clinicians. Extensive discussion afterwards about the state of the art of research and knowledge on drug resistance in human helminthiases.
Year(s) Of Engagement Activity 2017
 
Description Invited short talk at Innovative tools for NTD Research Exploiting Genomics at RVC London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Invited talk to discuss ways of integrating genomic approaches into NTD research by the London Centre for Neglected Tropical Disease Research. I spoke about our BUG project genomic analyses, and the parallels that could be used for NTD drug resistance research. My talk was entitled "Building genomic resources for gastrointestinal helminth biology and control".
Year(s) Of Engagement Activity 2017
 
Description Invited tak at International Congress of Parasitology, Deagu, Korea; 19-24th August 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented work on anthelminthic genetics to international audience of scientists and public health professionals.
Year(s) Of Engagement Activity 2018
 
Description Invited talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk was presented at the INRA annual conference Tours, France by Dr Stephen Doyle entitled "Building genomic resources for helminth biology and control"
Year(s) Of Engagement Activity 2016
 
Description Invited talk (keynote) at Anthelmintics III Meeting in Florida 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited talk on the use of a genetic cross to study anthelmintic resistance in a parasitic nematode of sheep, attended by roughly 100 participants from around the world, followed by good discussion regarding preliminary findings.
Year(s) Of Engagement Activity 2018
 
Description Invited talk at DIDE Seminar Series, Imperial College London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact I was invited to give a Departmental Seminar at the Department of infectious Disease and Epidemiology in Imperial College London. I spoke about my previous work in NTD genomics, and the benefits of using H. contortus genetics to understand anthelmintic resistance. The talk was entitled "Genomic insights into anthelmintic resistance".
Year(s) Of Engagement Activity 2017
 
Description Invited talk at Drug Design and Development conference (German Society for Parasitology) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited talk at drug design meeting which led to new connections in industry and academia and with postgraduate students.
Year(s) Of Engagement Activity 2017
 
Description NIH global neglected infectious diseases lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar at NIH NIAID, Washington; including webcast to other NIH intramural sites.
Year(s) Of Engagement Activity 2017
 
Description NSA young sheep farmer training workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact A workshop was held for young farmers on sustainable worm control in sheep, as part of the National Sheep Association sheep event, led by Dr Hannah Rose. 60 farmers attended and left with a better appreciation of the principles and practice of management to delay anthelmintic drug resistance. Participants reported improved knowledge and increased likelihood to implement practices to slow resistance development on their farms.
Year(s) Of Engagement Activity 2016
 
Description Paraveterinary training in Malawi. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact A series of training courses and workshops held for paravets in southern Malawi. Topics of roundworm control in cattle and small ruminants and anthelmintic resistance were covered.
Year(s) Of Engagement Activity 2017
 
Description Poster presentation at meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A poster was present by a PhD student associated with the BUG project at the annual AHDB research meeting. The audience here is varied both academic, policy makers and commercial.
Year(s) Of Engagement Activity 2016
 
Description Poster presentation at meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A poster was presented at a Jacques Monod Conference in Roscoff entitled "Genomic and transcriptomic changes in populations of parasitic nematode Haemonchus contortus following vaccine exposure"by Sallé G., Laing R., Cotton J.A., Holroyd N., Doyle S., Newlands G.F.J., Smith W.D., Britton C. and Devaney E.
Year(s) Of Engagement Activity 2016
 
Description Presentation at COMBAR COST Action 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk was presented describing the role of social sciences in influencing farmer behaviour with respect to anthelmintic resistance
Year(s) Of Engagement Activity 2018
 
Description Presentation at Graduate Women Scotland meeting by PhD student associated with BUG 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact PhD student presented a talk to Graduate Women Scotland meeting describing aims of project
Year(s) Of Engagement Activity 2016
 
Description Resistance Day at Glasgow University 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I coordinated a workshop at the Glasgow University on the Evolution and Ecology of Resistance to Biocides. Speakers were drawn from different research areas in the University with one international speaker from ETH Zurich.
Year(s) Of Engagement Activity 2016
 
Description Running to stand still; Barcelona 
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 was a workshop held under the auspices of BBSRC to discuss the evolution of drug resistance in healthcare and agriculture
Year(s) Of Engagement Activity 2016
 
Description SCOPS stand at NSA national sheep event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Dr Hannah Rose assisted at the SCOPS (sustainable control of parasites in sheep) stand at the NSA (national sheep association) national sheep event in June 2016. SCOPS manned a stand at which farmers and other attendees could obtain information on, and discuss, parasite control in sheep. Correct practical drenching technique was shown in a series of live demonstrations attended by total audience of several hundred. Outcomes were greater appreciation by farmers of correct treatment practices and increased knowledge of sustainable control principles and methods.
Year(s) Of Engagement Activity 2016
 
Description SCOPS steering group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dr Hannah Rose and Dr Eric Morgan reported by invitation to the SCOPS (sustainable control of parasites in sheep) steering group on using predictive models to target anthelmintic treatments and so reduce selection pressure for resistance through inappropriate use. A refined decision support tool for Nematodirus treatment was presented and dissemiantion plans for 2017 made, and extension of a similar approach to Haemonchus was discussed. Plans were made to deliver decision support tools for farmers, and to incorporate these tools into current best practice recommendations and policy.
Year(s) Of Engagement Activity 2017
 
Description School Visit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visited primary school as part of Schools Science Week to inform on parasitic infections which stimulated interest and discussion.
Year(s) Of Engagement Activity 2019
 
Description Short presentation by request, with discussion 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Roughly 30-40 farmers and others related to the industry attended a breeders meeting. One of the main articles for discussion was the use of faecal egg counts and IgA saliva as part of a rams estimated breeding value score. I was asked to give a short 20-30 minute presentation on strongyle egg counts and the use of IgA saliva to score for phenotypic resistance to parasitic nematodes, in particular T. circumcincta. The presentation stimulated a lively discussion and prompted further questions and debate afterwards. Following the meeting several farmers (in addition to those already doing so) submitted faecal samples for speciation of strongyles to Signet, who are responsible for generating these estimated breeding values.
Year(s) Of Engagement Activity 2017
 
Description Short talk - institute and lab talks. Also additional talks/presentations at small meetings relating to the BUG project. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Short presentations are given each year to other members of the institute and/or lab group. These include at least one yearly presentation to the institute on the research carried out as part of the PhD. These talks generally stimulate questions from the audience, and are useful in generating feedback and ideas for continuing analyses and research tasks within the PhD.
Year(s) Of Engagement Activity 2016,2017,2018
 
Description Short talk at Meiosis and Beyond Workshop, Earlham Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Attended and presented at a workshop focused on the study of meiosis. The aim was to gather a diverse group of researchers to identify key themes and technological challenges, with the intention to write an opinion / perspective manuscript on the subject. A skeleton draft of a manuscript was outlined on the day. I presented some aspects of data generated from the BUG project in a talk entitled "Construction of a genome-resequencing based genetic map reveals sporadic polyploidy in an outbred parasitic nematode".
Year(s) Of Engagement Activity 2018
URL http://www.earlham.ac.uk/meiosis-and-beyond
 
Description Short talk at conference Anthelmintic Resistance III 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A short talk was given at the international conference 'Anthelmintic Reisistance III' in Florida. Those present included researchers, postgraduate students and industry professionals. The talk described preliminary results from recent work using genome wide sequencing to identify genomic regions of selection following ivermectin treatment in a UK field population of T. circumcincta.
Year(s) Of Engagement Activity 2018
 
Description Short talk given to parasitologists within the University of Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Gave a 25 minute talk about the research methods and current findings from the project to other parasitologists within the institute at a 'Research Update Meeting'. These meetings are very well attended by parasitologists from a wide range of disciplines.
Year(s) Of Engagement Activity 2019
 
Description Talk at the British Association for the Advancement of Veterinary Parasitology Winter meeting, 10-11 December 2019, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dr Hannah Vineer presented a talk entitled "Weather and the development of anthelmintic resistant Haemonchus contortus"
Year(s) Of Engagement Activity 2019
 
Description The BUG consortium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented a poster at COMBAR, an EU COST Action on anthelmintic resistance
Year(s) Of Engagement Activity 2018
 
Description Three minute thesis talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact I gave a talk as part of the three minute thesis (3MT) competition at the University of Glasgow. There were about 25 people in the room. The talk was filmed, tweeted about by the 3MT group and others and will be loaded onto the University of Glasgow website in the future. The talk covered the reason behind the PhD and briefly mentioned the methods, and future outcomes.
Year(s) Of Engagement Activity 2019
URL https://www.gla.ac.uk/research/ourresearchenvironment/prs/pgrcoursesandevents/threeminutethesiscompe...
 
Description Twitter account 'SheepwormPhD' 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Twitter account set up primarily to reach farmers and vets for knowledge transfer and knowledge exchange. Currently the account has 96 followers, most of whom are within the UK and 13 of whom are new from the last 30 days. The most common word in their profiles is 'sheep'. Most tweets are either re-tweets of industry relevant information, or tweets about sheep/parasite talks or other activities related to work carried out as part of the PhD or wider BUG consortium project. Tweets in the last month ranged from 77 impressions to almost 4000. Actual engagement with the tweet ranged from 1 to 41.
Year(s) Of Engagement Activity 2018,2019
URL https://twitter.com/sheepwormPhD
 
Description Two prison visits to provide a teaching session to prison learners. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact On two separate occasions I went with Cell Block Science (https://news.st-andrews.ac.uk/archive/cell-block-science/) into HMP Shotts and HMP Low Moss to provide a session about sheep parasites and anthelmintic resistance to the prison learners. At each prison two sessions were run, reaching between about 6-10 learners at each session. A combination of powerpoint, discussion, and in-depth activities were used to stimulate learning and problem solving. Learners were taken from the concept of the disease understudy in this PhD, through the complexities of the nature of the disease, to actively planning with farm maps, anthelmintic efficacy data, species data and farm management data how they would manage the disease on their farm. Some learners were from a farming, or animal health background which meant that the information was directly applicable to them and should make a lasting impression for when they leave prison. All learners were actively engaged in the sessions and from the activities performed it was clear that the impact had been achieved.
Year(s) Of Engagement Activity 2018
URL https://twitter.com/sheepwormPhD/status/1060914897440120841
 
Description Workshop on worm control 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Within a workshop on best practice in worm control in sheep, which was funded by a SG project the audience was made aware of the BUG project and its goals.
Year(s) Of Engagement Activity 2017
 
Description Workshops for BBSRC Resistance highlight call 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I presented at two workshops to accompany the BBSRC Highlight call in Resistance in Agriculture
Year(s) Of Engagement Activity 2016