FLPing around aids behavioural adaptability in nematodes

Lead Research Organisation: Queen's University of Belfast
Department Name: Sch of Biological Sciences

Abstract

Nematodes are a success story in the Animal Kingdom and they are second only to the Arthropods in terms of numbers. The anatomy of a nematode is very simple - they only possess longitudinal muscles in their body wall and their nervous system comprises of ~300 nerve cells that are arranged in a similar pattern in species across the phylum. Despite this, they are complex, diverse and highly specialised animals. Indeed, one reason for their success is the diversity in their behaviour and their ability to survive in many different habitats throughout the world as both free-living and parasitic species. Nematodes can be divided into different clades based on their relatedness - the current train of thought is that there are five major clades (I-V). As parasites of livestock, nematodes can significantly impact the health and well-being of agricultural animals, thereby directly affecting productivity, economic return and animal welfare. For example, Haemonchus contortus is the most pathogenic nematode of sheep, leading to severe anaemia and sometimes death. As parasites of plants, nematodes can cause total destruction of plant material, and are a significant problem in many commercially important crops such as potato and tomato, amongst others. A key issue in the control of nematode parasites is that the drugs that are currently used to treat them are becoming less effective as the worms develop resistance. In fact, in some areas of the world (for example, parts of Scotland and New Zealand), sheep and cattle cannot be farmed simply because of parasite control problems. Therefore we need to search for novel drug targets so that livestock farming has a future both in the UK and further afield. In order to ensure survival a nematode must move, feed, and reproduce. Each of these behaviours rely on muscle, and are under the control of signalling molecules within the nervous system of the nematode. Unlike structure, the chemical make-up of the nematode nervous system is complex. One group of signalling molecules are the neuropeptides. In nematodes there are three main families of neuropeptides, the largest of which are known as the FMRFamide-like peptides or FLPs. FLPs have been shown to modulate feeding, reproduction and movement in many nematode species and therefore, the FLP signalling system is a potential novel drug target candidate. There are >70 FLPs in nematodes, and the same structures have been shown to be present in free-living and parasitic species. We don't know if these structures play similar roles in different nematode species. This information is important in order to select the 'best' candidates for drug targetting. For example, if an individual FLP was critical to the survival of one animal-parasite but not to another, then it would be a less attractive target than one that played an important role in several important nematode parasites. We have some preliminary evidence which points to functional differences in FLPs across the nematode phylum. This study plans to investigate the role of individual FLPs in nematodes by examining their distribution in the nervous system of a range of nematode species representing different clades and lifestyles and probing the effects of the FLPs on muscle-based behaviours. This research will increase our understanding of the FLP signalling system in nematodes, and comparative analyses will provide baseline data on the utility of FLP signalling as a target system for parasite control.

Technical Summary

Parasitic nematodes impose a major economic and welfare burden on livestock, with global economic losses associated with animal death, reduced growth and productivity, in addition to the costs associated with anthelmintic treatment. Unfortunately, the current spectrum of drugs used to treat nematode parasites of livestock are compromised by resistance, compounding the economic impact. The nematode neuromuscular system has proved to be a rich source of drug targets, as it is responsible for governing many aspects of nematode behaviour that ensure survival. Indeed, most of the current broad spectrum anthelmintics target the classical transmitter component of this system, and yet the neuropeptidergic system is as important to the normal behaviour of the nematode parasite. Significantly, this system will not be burdened by resistance. A major hurdle to exploitation of the neuropeptidergic system is the lack of functional validation of neuropeptides and their receptors in key parasite species. In this study we will employ multiple techniques to investigate the function of the largest family of nematode neuropeptides, the FMRFamide-like peptides (FLPs), and its conservation throughout phylum Nematoda. We will combine recent technical advances in neuropeptidomics and quantitative PCR with classical localization methodologies (ICC, ISH) to probe FLP and FLP receptor expression in a range of nematode species. In addition, we will use reverse genetics (RNA interference, deletion mutants), and a mixture of simple bioassays with computational behavioural platforms to investigate FLP and FLP receptor function. This will provide us with information on whether or not FLPs and their receptors are functionally conserved in different nematode species from divergent habitats or clades, and it will allow us to identify those receptors to which novel therapeutics can be directed.

Planned Impact

Parasitic helminths are a major threat to global food security, and have been estimated to cost the livestock industry worldwide more than $50 billion/annum. The treat-all application approach of broad-spectrum anthelmintics has been the primary method to control parasitic worms in livestock in the developed world for over 50 years, and has made the production of cheap and plentiful food to a growing world population feasible. New control strategies are urgently needed as anthelmintic resistance in nematode parasite populations is spreading globally, and this coupled to the restricted portfolio of new anthelmintics, means that in some parts of the world intensive livestock farming is not sustainable in the absence of new parasite control measures. The programme of research outlined in this proposal, through the discovery and validation of novel drug targets, will help inform industry, government and funding bodies about the potential of developing a more effective control strategy for parasitic worm diseases of livestock. The non-academic beneficiaries of this proposal will range from worldwide farming communities, who would benefit directly from the development of a novel chemotherapeutic for parasite control, to a range of pharmaceutical and biotechnology industries that will have the opportunity to further develop and/or commercialize new validated targets. The applicant (Mousley) has established connections with the Animal Health Industry via current and past research contracts and collaborations (Merial, Pfizer and Jansen Animal Health). Her contacts in these organisations would be in a position to advise on exploitation of the research findings. With respect to the reduction of anthelmintic use, the general public also demand safe, chemical residue reduced food, produced cost effectively from animals maintained in a welfare friendly environment, and therefore would benefit from a novel drug that required fewer applications. In addition, Levy bodies (including the Agriculture and Horticulture Development Board) and government will benefit from this applied research, which has the potential to shape future policy and strategy. The impact benefits of this programme will be revealed via website, media, public awareness events such as Science Weeks, Agricultural Shows and conferences. The UK applicant has experience in engaging the farming community through publications in Farming Journals and attendance at Agricultural shows. Public communication of our research in the UK will also be via stands, generic talks by research staff and academic staff at UCAS visits and Open Days to prospective students and parents in respective departments of the applicants. The integrated design of the programme and the questions being addressed should facilitate generation of at least one major headline publication with further impact capabilities. Publications from the research will be co-ordinated by Press and Public Relations Departments at QUB. In addition, the EU- and USA-based collaborators will further enhance international dissemination of the research findings worldwide.
 
Title Cover image International Journal for Parasitology 
Description Cover image for Volume 46, Issue 10 of International Journal for Parasitology - adult Ascaris suum. 
Type Of Art Image 
Year Produced 2015 
Impact International journal readership. Awareness of article/research focused on Ascaris suum. Publicity for RCUK funded research. 
URL http://www.sciencedirect.com/science/journal/00207519/45/11
 
Description SPECIFIC AIM 1: Examine flp-gene and FLP-receptor gene conservation in nematodes

Summary of progress: flp-gene and FLP-receptor gene conservation in nematodes has been examined using bioinformatics to trawl the genomic and transcriptomic datasets of 17 nematode species representing multiple clades and lifestyles. The data generated represents the most comprehensive insight into the flp and flp-GPCR complements of parasitic nematodes to date and have provided a database of conserved and unique nematode flp and flp-GPCR genes in free-living, animal-, plant- and human-parasitic nematodes.
A number of key findings have emerged from this work:
• Multiple nematode parasites appear to possess a reduced complement of C. elegans flp-gene
sequelogues.
• flp-gene complement appears to broadly map nematode clade division, with some exceptions.
• Some flp-genes are more highly conserved than others.
• Only one flp-gene (flp-31) appears to be parasite-specific.
• Known deorphanised C. elegans FLP-receptors are conserved in parasite species.
• Phylogenetic analysis reveals a further 13 putative flp-GPCR genes in nematode parasites.

The objectives outlined in Specific Aim 1 have been met by output #2, #5 and #10, detailed below.

SPECIFIC AIM 2: Compare nematode FLP and FLP receptor temporal and spatial expression patterns

Summary of progress: The expression patterns of multiple FLPs have been examined in key nematode species through the use of immunocytochemistry (ICC - custom raised antisera), and in situ hybridization (ISH) techniques in five key nematode species (Caenorhabditis elegans, Panagrellus redivivus, Globodera pallida, Haemonchus contortus, and Teladorsagia circumcincta). We have generated data on the specific expression of structurally-conserved FLPs, enabling direct comparisons between nematode species representing different clades and lifestyles (free-living, animal-, plant- and human-parasitic nematodes). Work on the expression (ISH) profile of flp-GPCRs is ongoing alongside an examination of tissue specific FLP expression profiles (peptidomics) and flp-GPCR tissue specific expression profiling (qPCR) in the animal parasitic nematode Ascaris suum. The work completed to date has demonstrated:
• Distinct neuronal localisation patterns for FLP-2, 11, 14, 31, and 32 (ICC) in five key nematode species
• Comparative expression patterns for flp-2, 12, 13, 31 (ISH) in the nervous system of G.
pallida.
• Comparative expression patterns of flp-11 and flp-32 across the five key nematode species highlighted above.
• A restricted and conserved pattern of localisation/expression (ICC/ISH) for FLP-11/flp-11 to one distinct neuronal cell body in the 5 key nematode species examined.
• A less restricted and variable localisation/expression pattern (ICC/ISH) for FLP-32/flp-32 in the 5 key nematode species examined.

The objectives outlined in Specific Aim 2 have been met by output #3, #4, #5, #9, #10, and #16, and #17 detailed below.

SPECIFIC AIM 3: Investigate motor-modulation by FLPs in distinct nematode species

Summary of progress: We have employed reverse genetics tools (RNA interference, RNAi) and a number of sensitive post-RNAi bioassays to measure nematode behaviour in both the plant parasitic nematode G. pallida and the animal parasitic nematode A. suum. To date we have:
(a) Generated data on the function of a highly conserved flp-gene, flp-32, and a novel putative flp-32 receptor in G. pallida. Key findings demonstrate that:
• The migration rate of G. pallida increases in Gp-flp-32-silenced worms
• The ability of G. pallida to infect potato plant root systems is enhanced in Gp-flp-32-silenced worms
• A novel putative Gp-flp-32 receptor (Gp-flp-32R) is expressed in G. pallida
• Gp-flp-32R-silenced worms also display an increase in migration rate.
• Gp-flp-32 plays an intrinsic role in the modulation of locomotory behaviour in G. pallida, and
putatively interacts with at least one novel G-protein coupled receptor (Gp-flp-32R).
• These data report the first functional characterisation of a parasitic nematode FLP-GPCR.
(b) Developed (and are currently optimising), a novel and robust RNAi platform in A. suum which will support flp- and flp-GPCR gene functional characterisation. The data show that:
• A.suum RNAi is readily achievable: Injection of dsRNA triggers knockdown of a range of gene
transcripts (100% percent success rate; >10 gene targets; highly reproducible)
• Multiple tissue types are susceptible: neuronal and muscle based genes are susceptible to RNAi
• RNAi response is capable of spreading: silencing is detected in areas of the worm that are most distant from the site of injection
• Silencing of validated drug targets is achievable (nicotinic acetylcholine receptor subunits)
• Double stranded (ds)RNA cocktail is as efficient as single dsRNA-approach
• Silencing persists for at least 8 days

The objectives outlined in Specific Aim 3 have been met by output #1, #3, #5, #6, #7, #8, #11, #12, #13, and #14 detailed below.

Specific Aim OUTPUTS:
1. Publication: McCoy C.J., Warnock N.D., Atkinson L.E., Atcheson E., Martin R.J., Robertson A.P., Maule A.G., Marks N.J., Mousley A. (2015). RNA interference in adult Ascaris suum --an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite. International Journal for Parasitology 45, 673-678. doi:0.1016/j.ijpara.2015.05.00
2. Publication: McCoy C.J., Atkinson L.E., Zamanian M., McVeigh P., Day T.A., Kimber M.J., Marks N.J., Maule A.G., Mousley A. (2014) New Insights into the FLPergic Complements of Parasitic Nematodes: informing deorphanisation approaches. EUPA Open Proteomics 3, 262-272.
3. Publication: Atkinson L.E., Stevenson M., McCoy C.J., Marks N.J., Fleming C., Zamanian M., Day T.A., Kimber M.J., Maule A.G., Mousley A. (2013) flp-32 Ligand/receptor silencing phenocopy faster plant pathogenic nematodes. PLOS Pathogens 9 (2):e1003169. doi: 10.1371/journal.ppat.1003169.
4. Publication (in preparation): Atkinson L.E., Miskelly I.R., Moffett C.L., McCoy C.J., Maule A.G., Marks N.J., Mousley A. Unraveling flp-11 / flp-32 Dichotomy in Nematodes. Prepared for imminent submission to ACS Chemical Neuroscience.
5. International conference invited speaker oral presentation: Mousley, A., Atkinson, L., McVeigh, P., McCoy, C., Warnock, N., Dalzell, J.J., Marks, N.J., Maule, A.G. Nematode Neuropeptides: From Sequence to Biology and Back. Anthelmintics: From Discovery to Resistance II San Diego 9-12 Feb 2016.
6. International conference oral presentation: McCoy C.J., Warnock N.D., Atkinson L.E., Atcheson E., Martin R.J., Robertson A.P., Maule A.G., Marks N.J., Mousley A. RNAi competency in adult Ascaris suum - potent, persistent and reproducible knockdown. American Society of Tropical Medicine and Hygiene: 64th Annual Meeting, Philadelphia, USA Oct 2015.
7. International conference oral presentation: McCoy C.J., Warnock N.D., Atkinson L.E., Atcheson E., Martin R.J., Robertson A.P., Maule A.G., Marks N.J., Mousley A. RNA interference in adult Ascaris suum --an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite. 25th International Conference of the World Association for the Advancement of Veterinary Parasitology, Liverpool, UK, Aug 2015.
8. International conference oral presentation: McCoy C.J., Warnock N.D., Atkinson L.E., Atcheson E., Martin R.J., Robertson A.P., Maule A.G., Marks N.J., Mousley A. RNA interference in adult Ascaris suum is potent, persistent and reproducible. The Center for Tropical and Emerging Global Diseases 25th Annual Symposium, UGA, USA, Apr 2015.
9. International conference poster and oral presentation: Atkinson L.E., Miskelly I.R., Moffett C.L., McCoy C.J., Maule A.G., Marks N.J., Mousley A. flp-11 / flp-32 Dichotomy in Nematodes: A Lesson in Drug Target Selection? Anthelmintics from Discovery to Resistance. San Francisco, USA, Feb 2014.
10. International conference poster and oral presentation: McCoy C.J., Atkinson L.E., Zamanian M., McVeigh P., Day T.A., Kimber M.J., Marks N.J., Maule A.G., Mousley A. FMRFamide-like peptide-GPCR Complements in Parasitic Nematodes, Anthelmintics from Discovery to Resistance, San Francisco, USA, Feb 2014.
11. International conference poster and oral presentation: McCoy C.J., Warnock N., Atkinson L.E., Maule A.G., Marks N.J., Mousley A. Building a Reverse Genetics Platform for Novel Drug Discovery in Nematode Parasites. Anthelmintics from Discovery to Resistance, San Francisco, USA, Feb 2014.
12. National conference poster and oral presentation: McCoy C.J., Warnock N., Atkinson L.E., Maule A.G., Marks N.J., Mousley A. RNA Interference in Adult Ascaris suum; New Tricks for and Old model. WAAVP Perth, Australia, Aug 2013.
13. National conference oral presentation: McCoy C.J., Warnock N., Atkinson L.E., Maule A.G., Marks N.J., Mousley A. RNA Interference in Adult Ascaris suum; A tool to probe neuromuscular gene function. British Society for Parasitology, Bristol, UK, April 2013.
14. National conference oral presentation: McCoy C.J., Warnock N.D., Atkinson L.E., Maule A.G., Marks N.J., Mousley A. RNAi in adult Ascaris suum. British Society for Parasitology, Glasgow, UK, April 2012.
15. National conference oral presentation: Atkinson L.E., Stevenson M., Fleming C., Zamanian M., Kimber M.J., Marks N.J., Maule A.G., Mousley A. FMRFamide like peptide-11 function and localisation in Globodera pallida. British Society for Parasitology, Glasgow, UK, April 2012.
16. National conference poster presentation: Atkinson L.E., Stevenson M., Fleming C., Zamanian M., Kimber M.J., Marks N.J., Maule A.G., Mousley A. Identification and validation of novel drug targets in nematodes of agricultural importance. Safe food Chemical Residues in Food Knowledge Networks Anthelmintics: Emerging Issues with Drug Residues and Drug Resistance, Dublin, Ireland, Feb 2012.
17. National conference oral presentation: Atkinson L.E., Marks N.J., Maule A.G., Mousley A. Comparative Analyses of FMRFamide-like Peptide Expression and Function in Nematodes. British Society for Parasitology, Nottingham, UK, April 2011.
Exploitation Route Outcomes from BBH0194721 have been/will be taken forward in the following ways:

NON ACADEMIC:
• Industry/pharmaceuticals/biotechnology: Research data generated through BB/H019472/1 have contributed to further research funding involving the pharmaceutical industry (BBSRC IP Award BB/MO10392/1 with Merial Animal Health as the industrial partner). This will contribute to further research data which will aid the further development and commercialization of new validated drug targets and the distribution of novel veterinary pharmaceutical products in the future.
• General public/farming communities: will benefit from research outcomes in the form of basic research which will contribute to the development of more effective control strategies for parasitic nematodes of veterinary and economic importance. This will have direct economic impacts on animal health. Farmers have also benefitted in the form of community outreach activities where research data has been, and will continue to be, communicated through attendance and participated in local agricultural events (e.g. presentation at NI Pig Event, attendance at local Agricultural Show, interaction with farmers). This has helped the farmer to have a greater understanding of the impact of nematode parasites on animal health and appreciate the importance of scientific research.
• General public/food and drink industry: will benefit from the research outcomes as a consequence of pharmaceutical interest in the research data generated. If these data contribute to new pharmaceuticals which enhance animal yields this will help meet a growing public demand for cost-effective food production.
• Policy: Going forward government and levy bodies will benefit from the research in the form of enhanced information with which to aid shaping future agricultural strategy and policy.

ACADEMIC:
• Education: research outcomes have had direct impact in the educational sector in the form of engagement activities with primary (Primary Life Sciences Scheme) and secondary level students (Careers events, Work placements) in addition to tertiary level students (undergraduate, MSc, PhD) who have become aware of the importance of research in our society by communication of the research project and outcomes. In addition the outcomes from this research have facilitated research-led teaching for undergraduate students at QUB.
• Research: the outcomes from this work have been published (with additional publications in progress) and presented at national and international conferences. This has facilitated new collaborations and provided opportunity for a further funding stream to continue the identification and validation of novel chemotherapeutic targets for nematode parasites.
Sectors Agriculture, Food and Drink,Education,Pharmaceuticals and Medical Biotechnology

 
Description Economic and Societal Impact (ongoing): Potential Economic Impact: Research data generated through BB/H019472/1 have facilitated additional research funding through a BBSRC IP Award (BB/MO10392/1) with Merial Animal Health as the industrial partner. This will allow the researchers / pharma company to pursue targets identified through BB/H019472/1 (and other novel targets) as potential control candidates which will aid the further development and commercialization of new validated drug targets and the distribution of novel veterinary pharmaceutical products in the future. The direct link with a pharmaceutical company will potentially progress this project towards achieving economic impact in the future. Potential Societal Impact: Farming communities: in the context of the additional funding stream described above, the farming community will benefit from research outcomes in the form of the development of more effective control strategies for parasitic nematodes of veterinary and economic importance. This will have direct economic impacts on animal health and farmer returns. Farmers have also already benefitted in the form of community outreach activities where research data has been, and will continue to be, communicated through attendance and participated in local agricultural events (e.g. presentation at NI Pig Event, attendance at local Agricultural Show, interaction with farmers). This has helped the farmer to have a greater understanding of the impact of nematode parasites on animal health and appreciate the importance of scientific research. Educators and Students: the research outcomes from BB/H019472/1 have already had a direct impact in the educational sector through the engagement with primary school students (via Primary Life Sciences Scheme) and secondary level students and their teachers (careers events, work placements, school visits). In addition, the research linked to BB/H019472/1 has been presented to tertiary level students (undergraduate-, MSc-, PhD-level). In this context, students have learnt about the importance of scientific research in general, in addition to specifics associated with the impact of nematode parasites on agriculture in the UK.
Sector Agriculture, Food and Drink,Education,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description BBSRC IPA (Responsive Mode)
Amount £259,499 (GBP)
Funding ID BB/M010392/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2015 
End 07/2018
 
Description Department for Employment and Learning PhD studentship
Amount £70,000 (GBP)
Organisation Government of Northern Ireland 
Department Department for Employment and Learning Northern Ireland (DELNI)
Sector Public
Country United Kingdom
Start 10/2011 
End 11/2014
 
Description Department of Agriculture and Rural Development Northern Ireland Studentship Scheme
Amount £70,000 (GBP)
Organisation Department of Agriculture and Rural Development (DARDNI) 
Sector Public
Country United Kingdom
Start 10/2014 
End 10/2017
 
Description Identification of Parasite Derived Antibacterial Agents to Tackle Emerging Antimicrobial Resistance and Reduce Antibiotic Use in Livestock
Amount £70,000 (GBP)
Organisation Government of Northern Ireland 
Department Department of Agriculture, Environment and Rural Affairs
Sector Public
Country United Kingdom
Start 10/2018 
End 08/2021
 
Description Merial Animal Health Research Award
Amount £82,166 (GBP)
Organisation Sanofi 
Department Merial Plc
Sector Private
Country Global
Start 08/2015 
End 07/2018
 
Description New Insights into the FLPergic Complements of Parasitic Nematodes: informing deorphanisation approaches 
Organisation Iowa State University
Country United States 
Sector Academic/University 
PI Contribution Contributed original data for the publication
Collaborator Contribution Collaboration contributed original data for the publication
Impact Publication output
Start Year 2010
 
Description RNA interference in adult ascaris suum--an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite. 
Organisation Iowa State University
Country United States 
Sector Academic/University 
PI Contribution Ascaris RNAi data for publication
Collaborator Contribution Host of PhD student to perform geographical isolate comparison of RNAi susceptibility
Impact Publication: RNA interference in adult Ascaris suum--an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite. Int J Parasitol. 2015 Sep;45(11):673-8. doi: 10.1016/j.ijpara.2015.05.003.
Start Year 2014
 
Description BALLYCLARE ALC CAREERS EVENT (27TH JANUARY 2016) 
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 CAREERS EVENT FOR KEY STAGE 3, YEAR 6, 7 AND YEAR 8 SCHOOL LEAVERS. Purpose was to promote Biological Sciences pathways at Queen's University Belfast and to engage students in BBSRC-funded research activity
Year(s) Of Engagement Activity 2016
 
Description BALMORAL SHOW INTERACTIVE DISPLAY 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Local Agricultural Show (18th May 2018). Communication of BBSRC funded research projects. Education of local agricultural personnel and public about the impact of agricultural parasites.
Year(s) Of Engagement Activity 2018
 
Description Invited Speaker: Royal Microscopical Society Meeting 2011 (27-28 January 2011); Bioimaging as a tool to aid the identification and validation of drug target candidates in parasitic helminths 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Parasitic helminths [phyla Nematoda (roundworms) and Platyhelminthes (flatworms)] represent a growing problem as disease-causing agents in humans and impose a major economic and welfare burden on livestock, with global losses associated with animal death, growth retardation, and reduced productivity. Unfortunately, the current spectrum of drugs used to treat helminth parasites are compromised by resistance, such that new control strategies are urgently needed. The helminth neuromuscular system is important in controlling a range of behaviours that are critical to worm survival and therefore represents a potential source of novel drug targets. Whilst parasite neuromusclulature is a proven drug target, most of the drugs that target this system act via the classical signalling pathways, leaving the neuropeptidergic component as an untapped resource. The recent surge in genomic and transcriptomic datasets for helminth parasites has facilitated the identification of candidate drug targets in distinct components of the neuropeptidergic signalling pathway including (i) enzymes involved in generation of active peptides (ii) receptors and (iii) enzymes responsible for peptide degradation. A major hurdle to the validation of these drug target candidates is the lack of functional information on the importance of the target to the survival or success of the parasite. Bioimaging is a central tool in the validation process. It offers a method with which potential drug targets can be localized providing information on their expression in therapeutically-relevant organ systems (e.g. reproductive system, digestive system) and consequently clues on function, and is a robust platform for the validation of reverse genetics (RNA interference) experiments.

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description It's a Wormy World! (1st March 2012; RCUK CPD for Secondary Level Science Teachers (W5, Belfast); 'Applied Genetics'; invited speaker and workshop coordinator 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact It's a Wormy World (1st March 2012; RCUK CPD for Secondary Level Science Teachers (W5, Belfast); 'Applied Genetics'; invited speaker and workshop coordinator: ~50 teachers attended the event, introduced the subject, showcased our RCUK-funded project (BB/H019472/1). Stimulated interest from teachers; received invites to schools to engage students.
Year(s) Of Engagement Activity 2012
 
Description Molecular Helminthology: An Integrated Approach (POSTER, 19-22 March 2017, Cape Cod, MA, USA) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Abstract - The future of novel drug target discovery for neglected tropical diseases is reliant on the development of functional genomics platforms in key pathogens. While progress in this area has been slow for nematode parasites, where many species are reported to be intractable to current reverse genetics methodologies, a handful appear compatible with advanced molecular tools. Bolstered by a wealth of genomic/transcriptomic information, and increasing affordability of Next Generation Sequencing, the discovery and validation of novel drug targets is becoming a less distant prospect in Ascaris suum where significant progress has been made in the development of functional genomics tools.
Neuropeptide signalling system biology has been a central focus of nematode drug target discovery. Integrating 'omics' resources in A. suum has provided new opportunities for neuropeptide G-protein coupled receptor (GPCR) deorphanisation. In this study we combined the experimental tractability of A. suum with RNA-seq to identify the neuropeptide/neuropeptide GPCR complements of two distinct, functionally important tissues: (i) the ovijector, and (ii) the body wall muscle. Tissue specific RNA-seq libraries were generated (n=3) and analysed using the Tuxedo pipeline. Overexpression and functional enrichment analysis revealed 871 genes overexpressed in the ovijector, including 33 genes involved in GPCR activity. A cohort of at least five FMRF-amide like peptide GPCRs (flp-GPCR) were identified in the ovijector tissue alongside six putative ligands (flps) in the body wall muscle containing the neuronal cell bodies which innervate ovijector tissue. Immunlocalisation studies unequivocally confirmed the presence of specific FLPs in the neuronal cell bodies innervating the ovijector tissue. These data will direct functional deorphanisation attempts in A. suum using RNA interference (RNAi) coupled with a post-RNAi ovijector bioassay. Together these 'omic' approaches bring us closer to the prospect of ex vivo GPCR deorphanisation in animal parasitic nematodes and provide fresh hope for novel drug target identification.
Year(s) Of Engagement Activity 2017
URL https://www.elsevier.com/events/conferences/molecular-helminthology-an-integrated-approach
 
Description Multi-Omics Approaches to Unravelling the Complexity of Neuropeptide Signalling in Nematodes (INVITED SPEAKER: British Society for Parasitology, Belfast, 2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Invited presentation at the BSP Autumn symposium 2019 in Belfast, UK
Year(s) Of Engagement Activity 2019
 
Description Nematode Neuropeptides: From Sequence to Biology and Back (INVITED SPEAKER: Anthelmintics: Discovery to Resistance II, San Diego Feb 9th - 12th, 2016) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Nematode Neuropeptides: From Sequence to Biology and Back

Angela Mousley, Louise Atkinson, Paul McVeigh, Ciaran McCoy, Neil Warnock, Johnathan Dalzell, Nikki Marks, Aaron Maule

Parasitology Research Group, Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, UK

We have maintained a long-standing interest in helminth neurobiology at Queen's University Belfast that stemmed from the early work of Professor D.W. Halton, and continued through research activity in the Maule and Marks laboratories. In the early days, localisation of neuropeptides through immunocytochemical techniques in association with classical biochemical characterisation methods, PCR-based gene detection tools, and muscle-based functional assay systems
provided data on the importance of neuropeptides to helminth biology, and flagged the candidature of the neuropeptidergic system as an anthelmintic target. Despite this, our understanding of the biology of neuropeptides and their signalling systems, especially in key therapeutically relevant pathogens, is limited. The recent growth in genomic and transcriptomic datasets for parasitic helminths, and positive shift in the cost and accessibility of gene sequencing technologies, provides a welcome gateway to the identification of neuropeptides, their receptors and pathway components. In addition, progress in the development of parasite-focused reverse genetics tools offers the ability to manipulate target function in key pathogens and opportunities for novel anthelmintic discovery. This presentation will provide an overview of the efforts to progress the identification and validation of neuropeptidergic system-derived drug target candidates in nematode parasites, and highlight recent advances in our understanding of neuropeptide biology across the phylum Nematoda.
Year(s) Of Engagement Activity 2016
 
Description Oral Presentation: The Center for Tropical & Emerging Global Diseases 25th Annual Symposoim, UGA, USA, 28-29th April 2015; RNA interference in adult Ascaris suum is potent, persistent and reproducible. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact RNA interference in adult Ascaris suum is potent, persistent and reproducible.
Year(s) Of Engagement Activity 2015
 
Description Oral Presentation: American Society of Tropical Medicine and Hygiene: 64th Annual Meeting, Philadelphia, USA, 25-29 October 2015; RNAi competency in adult Ascaris suum - potent, persistent and reproducible knockdown 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact RNAi competency in adult Ascaris suum - potent, persistent and reproducible knockdown
Year(s) Of Engagement Activity 2015
 
Description Oral Presentation: BSP Spring Meeting 2011, Nottingham, Uk, 12-14 April 2011; Comparative analyses of FMRFamide-like peptide expression and function in nematodes. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Nematode FMRFamide-like peptides (FLPs) are structurally conserved between species irrespective of clade or lifestyle. However, through the use of immunocytochemistry (ICC), in situ hybridisation (ISH), mass spectrometry, and reporter flp-gene constructs, published datasets have provided preliminary information on inter-species flp-gene- and FLP-expression and highlight hyper-variability between the localisation patterns of homologous FLP sequences. We believe that this FLP variation represents what could be genuine functional differences that ultimately contribute to nematode behavioural adaptability and their success as a phylum. In this study we employ ICC and ISH to investigate the differential expression patterns of two of the most highly conserved flp-genes (flp-11 and flp-13) in a range of nematode species including the clade IV plant parasitic nematodes, Globodera pallida and Meloidogyne incognita, and the clade V free-living nematode, Panagrellus redivivus. In addition RNA interference (RNAi) of flp-11 and flp-13 in G. pallida and M. incognita provides information on the function of these peptides as determined by motility- and chemosensory-based post-gene silencing bioassays. Preliminary results highlight both differences and similarities in flp-11 and flp-13 expression patterns and function between different nematode species. This research provides baseline data on the utility of FLP signalling as a target system for broad-spectrum nematode parasite control.

No actual impacts realised yet
Year(s) Of Engagement Activity 2011
 
Description Oral Presentation: BSP Spring Meeting 2012 Strathclyde (3-5 April 2012); FMRFamide like peptide-11 function and localisation in Globodera pallida; 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Novel control strategies for plant parasitic nematodes, including the potato cyst nematode Globodera pallida, are a primary concern due to nematicide withdrawal. The neuropeptide signalling system is an attractive resource in the search for novel chemotherapeutic control targets, as it modulates sensory and motor functions. The FMRFamide-like peptides (FLPs) form one of the largest families of neuropeptides, and are structurally conserved across nematode species, generating potential for a broad-spectrum drug target within the FLPergic system. flp-11 (RNxLVRFamide) is a commonly expressed FLP, encoding at least one, but up to three distinct peptides, in as many as 12 nematode species across Clades III, IV and V. This study investigates the role of flp-11 in G. pallida using a range of techniques to show that (i) Gp-flp-11 encodes a single peptide - AMRNALVRFamide, (ii) Gp-flp-11 is expressed in the nervous system, (iii) worm movement is increased in Gp-flp-11 silenced worms, (iv) the ability of Gp-flp-11 silenced worms to infect potato plants is enhanced, (v) a novel Gp-flp-11 receptor (Gp-flp-11 R) is expressed in G. pallida, and (vi) Gp-flp-11 R silenced worms also display increased movement. This work indicates that Gp-flp-11 and Gp-flp-11 R interact, and play a neuromodulatory role in G. pallida.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description Oral Presentation: BSP Spring Meeting Bristol 2013, 8-11 April 2013; RNA interference in adult Ascaris suum: A tool to probe neuromuscular gene function 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral presentation generated interest in the research activity and provided ideas for continuation of work

International recognition of research activity
Year(s) Of Engagement Activity 2013
 
Description Parasitic Nematode Functional Genomics - fit for purpose? (INVITED SPEAKER: AAVP 2016 Annual Meeting San Antonio, USA, 5-9th August 2016) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Parasitic Nematode Functional Genomics - fit for purpose?
Angela Mousley, Louise Atkinson, Ciaran McCoy, Nikki Marks, Aaron Maule
Parasitology Research Group, Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, UK
The recent growth in genomic, transcriptomic and proteomic datasets for parasitic nematodes provides a welcome gateway to the identification of putative drug targets, vaccine candidates, and diagnostic biomarkers. Indeed, omics-directed approaches to drug target identification have become widely adopted drug-finding strategies for human therapeutics, and have begun in earnest for nematode parasites where a cohort of 'druggable' targets, believed to have chemotherapeutic appeal due to their predicted 'essentiality', have been identified and prioritized in key nematode pathogens including Haemonchus contortus, Ascaris suum and Brugia malayi through in silico analyses. Despite this, a key hurdle to the exploitation of putative targets is the absence of validation tools that allow the manipulation of target function in therapeutically-relevant pathogens. Reverse genetics tools have advanced to the stage where sophisticated methods of transgenesis, gene silencing (RNA interference), and genome editing (CRISPR/Cas9 technology) are established experimental tools that are being applied to probe the biology of many organisms. Their application to nematode parasites has been eagerly awaited; however translation of these technologies has either been difficult or is in early stages of development, such that their potential to novel drug discovery in the parasitology discipline is yet to be realised. This presentation provides an overview of the genetic manipulation tools that are currently available for use in parasitic nematodes, and evaluates the advantages and limitations of these tools to the discovery of novel control targets.
Year(s) Of Engagement Activity 2016
 
Description Poster Presentation: Chemical Residues in Food Knowledge Networks Annual Conference: Anthelmintics Emerging Issues with Drug Residues and Drug Resistance, Dublin, ROI, 21st February 2012; Identification and validation of novel drug targets in nematodes of agricultural importance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Nematode parasites pose a major threat to livestock and plant crop health and productivity. Current control strategies for nematode parasites of agricultural importance are limited to a small cohort of drugs upon which farming has become reliant. However, as anthelmintic resistance develops and residue concerns emerge, the need to develop novel control strategies intensifies with particular emphasis on target spectrum. Nematode parasite FMRFamide-like peptide (FLP) signalling is an attractive target system for novel control options as FLPs are structurally conserved between species irrespective of lifestyle. However, the broad-spectrum utility of drugs directed against FLP signalling targets can only be determined by comparative functional analyses in multiple, divergent pathogenic species. Here we use a range of analysis tools to investigate the utility of the FLP signalling system for nematode parasite control. We report the differential expression patterns of some of the most highly conserved flp-genes (flp-11 and 13) in nematode species including the plant parasitic nematode Globodera pallida. RNA interference of flp-11 and a putative flp-11 receptor in G. pallida provides validation of target potential. Results provide data on the utility of FLP signalling as a source for broad-spectrum parasite control targets.

No actual impacts realised yet
Year(s) Of Engagement Activity 2012
 
Description Poster Presentation; BSP Spring Meeting 2012, Strathclyde, 3-5 April 2012; RNA interference in Adult Ascaris suum 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact RNA interference (RNAi) is a reverse genetics technique that represents a valuable method of elucidating gene function. In parasitic nematodes, the efficiency of RNAi varies between species and lifestage. Recent successes in invoking RNAi responses in the larval stages of Ascaris suum provides an opportunity to validate potential drug target candidates and to further probe the biology of Ascaris. This poster reports efforts to establish an RNAi platform in adult A. suum. The approach employed includes the examination of four target gene transcripts whose selection was based on: (i) transcript abundance, (ii) expression and localization patterns, and iii) previous success as RNAi targets in animal and human parasitic nematode gene silencing experiments. dsRNAs were injected into the pseudocoelomic cavity of adult A. suum and changes in transcript levels post-RNAi were assessed using quantitative real time PCR. Specific, potent and statistically significant transcript knockdown (>70%, n_4) was induced in two of the four genes targeted; elongation factor (As-eft-1) and pyrophosphatase (As-ppase). This data demonstrates, for the first time, that adult A. suum possesses a functional RNAi pathway and that a simple injection method of dsRNA delivery was sufficient to trigger an RNAi response. These results highlight the potential for the development of a robust platform for the investigation of gene function in A. suum.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
URL http://www.pa2online.org/abstract/abstract.jsp?abid=29903&kw=GABA&author=chen%20y&cat=-1&period=48
 
Description Poster and Oral Presentation: Anthelmintics: From Discovery to Resistance I, San Franscisco, USA, 5-7 February 2014; Building a reverse genetics platform for novel drug discovery in nematode parasites 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Nematode parasites undermine farm animal health resulting in economic losses that reduce significantly the profitability of the agricultural industry. Effective treatment options for livestock parasites are limited to chemotherapeutics that are subject to resistance pressures. As a result, future sustained control is dependent on the development of vaccines and/or drugs with novel modes of action. This relies on the establishment of drug discovery platforms in key parasites that facilitate drug target identification and validation. RNA interference (RNAi) is an appealing target discovery tool but its utility to the validation of drug targets in nematode parasites is limited because of their variable sensitivity to the available methodologies. Potential reasons for this relate to the inability to achieve optimized conditions that facilitate parasite culture / maintenance in vitro for prolonged periods of time, and appropriate trigger delivery methods. Ascaris suum, a nematode parasite of pigs, is an important veterinary-parasite model and a zoonotic pathogen. Successful RNAi has been reported in L3 larval stage A. suum and we have demonstrated its utility in adult A. suum. Here we report the optimization of an RNAi platform for adult A. suum that includes: (i) identification of the biotic and abiotic factors influencing adult A. suum vigour during in vitro maintenance; (ii) identification of robust methods for RNAi trigger delivery; (iii) approaches to the elucidation of RNAi-associated phenotypes. The optimization of an RNAi platform in adult A. suum has significant appeal in providing a route to target validation for parasitic nematodes.

No actual impacts realised yet
Year(s) Of Engagement Activity 2014
 
Description Poster and Oral Presentation: Anthelmintics: From Discovery to Resistance I, San Franscisco, USA, 5-7 February 2014; FMRFamide-like peptide-GPCR complements in parasitic nematodes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation generated interest in research project and initiated novel collaboration

no actual impacts realised to date
Year(s) Of Engagement Activity 2014
 
Description Poster and Oral Presentation: Anthelmintics: From Discovery to Resistance I, San Franscisco, USA, 5-7 February 2014; flp-11 / flp-32 Dichotomy in nematodes: A lesson in drug target selection? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation poster presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Growing deficiencies in nematode parasite control demand more vigorous target validation efforts to underpin anthelmintic discovery and screening programs. Most front-line anthelmintics disrupt parasite behavior through the dysregulation of classical signaling processes and encourage further interrogation of neuromuscular function for new targets. FMRFamide-like peptide (FLPs) signaling systems are core to nematode neuromuscular function and remain unexploited for parasite control. Some of our discovery efforts associated with nematode FLP/FLP receptor biology have uncovered subtle complexities that could compromise target selection in the absence of basic biology data - we present one example of this here. flp-11 is reported to be the most widely expressed flp in Caenorhabditis elegans and shows pan-phylum occurrence, promoting the appeal of the FLP-11 receptor as a putative drug target. A second gene (flp-32) encodes the homologous FLP AMRNALVRFamide, leading us to compare and contrast flp-11 and -32 biology. We found that: (i) flp-11 is not the most widely expressed flp in C. elegans; (ii) flp-11 displays a conserved and restricted expression pattern across nematode clades and lifestyles; (iii) multiple nematodes express both flp-11 and flp-32; (iv) flp-32 displays a broader and less conserved expression pattern in nematodes. Based on C. elegans data, the FLP-11 receptor had appeared to be an appealing target. However, the work here indicates that relying on C. elegans to inform target selection in parasites could lead to erroneous target prioritization. Even for highly conserved neuronal genes, biological data to support drug target value should be derived from parasitic nematodes

No actual impacts realised yet
Year(s) Of Engagement Activity 2014
 
Description Poster and Oral Presentation: WAAVP 2013, Perth, Australia, 25-29 August 2013; RNA interference in adult Ascaris suum: New Tricks For An Old Model 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact RNA interference (RNAi) is a reverse genetics technique which can be utilized to probe target gene function and to validate novel antiparasite-drug targets. The efficiency of RNAi in nematodes varies between species, life-stage, and gene target. The large size of Ascaris suum has facilitated its development as a key model species for nematode parasite biochemistry, neurobiology and physiology research, driving discovery biology and comparative studies with the free-living model Caenorhabditis elegans. Whilst RNAi has been reported in L3 larval stage A. suum, it has not been demonstrated in adults, limiting the utility of this gene silencing tool. Here we report the development of an RNAi platform for adult A. suum. Double stranded (ds)RNAs targeting genes expressed in a variety of tissue types (nerve, muscle, all cell types) were injected into the pseudocoelomic cavity of adult female A. suum; successful induction of RNAi was determined by monitoring target-gene transcript levels, encoded protein expression and worm phenotype. The data presented demonstrate: (i) a functional RNAi pathway in adult A. suum that can be triggered by the injection of dsRNA into the pseudocoel; (ii) the RNAi-susceptibility of target genes with disparate expression patterns (expressed in nerves, in muscles or ubiquitously); and, (iii) the ability to induce RNAi in tissues remote from the site of dsRNA injection. The optimisation of an RNAi platform in adult A. suum has significant appeal due to its tractability as a model for experimentation, the availability of genomic/transcriptomic resources and its negative impacts on food security and human health.

no actual impacts realised to date
Year(s) Of Engagement Activity 2013
 
Description Primary Life Sciences Scheme (Jan-April 2015; Dec-March 2016) 
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 Primary Life Sciences Scheme (Jan-April 2015; Dec-March 2016)
Worm watch: program delivered to primary level students to engage in scientific research. The purpose of the program was to engage the students in scientific research (specifically worm biology) and to promote STEM in primary schools. The teacher responsible for the class has requested that the scheme is continued in the future.
Year(s) Of Engagement Activity 2015,2016
 
Description RNA interference as a receptor deorphanisation tool in plant pathogenic nematodes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Plant pathogenic nematodes (PPNs) impose a significant economic burden on plant cultivation efforts worldwide. Recent estimates predict losses across all sectors of approximately $125 billion annually. Conventionally, an integrated approach to PPN management has relied heavily on various nematicides. As environmental concerns rise over the systemic effects of sustained nematicide use, withdrawal has left a significant shortcoming in our ability to manage this problem and highlights the need for novel control strategies.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description Royal Society Conference - Evolution and functional biology of neuropeptide signalling: from genomes to behaviour (INVITED SPEAKER, UK, 13-14th March 2017; The development of Functional Genomics Platforms for nematode pathogens: informing the biology of neuropeptides and their receptors) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Abstract:
Traditional approaches to the discovery, localisation and functional characterisation of nematode neuropeptides have included immunocytochemical techniques, classical biochemical characterisation methods, PCR-based gene detection tools, and muscle-based physiology assays. The data generated highlighted the importance of neuropeptides to nematode biology, and flagged the candidature of the neuropeptidergic system as a putative anthelmintic target. More recently, these datasets have been enhanced by the omic-analyses of nematode genome, transcriptome and peptidome datasets enabling the identification and prioritization of neuropeptides and their receptors that exhibit therapeutic appeal, but are not yet validated. Unfortunately, the development of functional biology tools in nematode parasites has not kept pace. Indeed, a key hurdle to the exploitation of putative targets is the absence of tools that allow the elucidation of target function in therapeutically-relevant nematode pathogens. Broadly, reverse genetics is being applied to probe the biology of many organisms through sophisticated methods of transgenesis, gene silencing (RNA interference), and genome editing (CRISPR/Cas9 technology). The application of these experimental tools to nematode parasites has been eagerly awaited; however their translation has either been difficult or is in early stages of development, such that their impact on novel drug discovery for the control of nematode pathogens is yet to be realised. This presentation provides an overview of Functional Genomics Platforms that are currently available for use in parasitic nematodes, and describes progress in their application to the understanding of the neuropeptidergic system.
Year(s) Of Engagement Activity 2017
URL https://royalsociety.org/science-events-and-lectures/2017/03/neuropeptide-signalling/
 
Description Royal Society Conference - Evolution and functional biology of neuropeptide signalling: from genomes to behaviour (POSTER, UK, 13-14th March 2017; The development of Functional Genomics Platforms for nematode pathogens: informing the biology of neuropeptides and their receptors) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Abstract - The neuropeptidergic system is a putative drug target repository for the control of nematode pathogens. Omics approaches have identified >250 nematode neuropeptides, and a number of neuropeptide G-protein coupled receptors (GPCRs). In vivo deorphanisation in nematode parasites has proven difficult; progress is reliant on the development of reverse genetics methodologies which allow putative ligand-receptor pairs to be identified. Ascaris suum offers an opportunity for a novel approach to neuropeptide receptor deorphanisation in a nematode parasite, through the integration of tissue-specific omics-derived data and the ability to probe target-, and tissue-specific gene function. This study describes the identification of neuropeptide/neuropeptide GPCR complements using RNAseq of two distinct A. suum tissues, the ovijector, and body wall muscle (nerve process originating in the body wall innervate the ovijector). 871 genes are overexpressed in the ovijector, including 33 genes involved in GPCR activity. Within one of the largest families of nematode neuropeptides (FMRF-amide like peptides, FLPs), at least five putative flp-GPCRs were identified in the ovijector, and six flps in the body wall that are hypothesised to be their cognate ligands. These data will direct functional deorphanisation attempts in A. suum using RNA interference (RNAi) coupled with a post-RNAi ovijector bioassay.
Year(s) Of Engagement Activity 2017
URL https://www.elsevier.com/events/conferences/molecular-helminthology-an-integrated-approach
 
Description STEMNET / SOCIETY OF BIOLOGY STEM CAREERS EVENT (24TH FEBRUARY 2016) 
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 Lecture on the Applications of DNA technology followed by careers event. Purpose was to engage students in current research activity and to promote interest in STEM subjects. Students were engaged with careers advice.
Year(s) Of Engagement Activity 2016
 
Description Silence - The Route to Parasite Control (1st March 2012; RCUK CPD for Secondary Level Science Teachers (W5, Belfast); 'Applied Genetics'; invited speaker and workshop coordinator 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Talk sparked discussion among teachers and research staff and developed ideas for teaching science in a school setting

After the talk a number of school students visited our lab on work experience
Year(s) Of Engagement Activity 2012
 
Description WAAVP conference (Liverpool UK 16-20 August 2015; Ascaris suum: A Novel Functional Genomics Platform for Nematode Parasites with Potential for Organism-, Tissue- and Cell-level Drug Target Validation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Abstract:
Year(s) Of Engagement Activity 2015
 
Description Workshop/Training Course: Helminth Genomics and Transcriptomics Bioinformatics Course, The Genome Institute, Washington University, St. Louis, USA (September 2015) 
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 Genomics, Transcriptomics and Bioinformatics workshop
Year(s) Of Engagement Activity 2015
 
Description Workshop/Training Course: Next Generation Sequencing Course, Manchester, April 2015 
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 Next Generation Sequencing Course
Year(s) Of Engagement Activity 2015