Beyond the Connectome: Unravelling Neuropeptide Signalling in Parasitic Nematodes to Inform Drug Discovery Pipelines

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

Abstract

Nematodes, or roundworms, are highly successful invertebrates. There are >25,000 species which can be either free-living or parasites of humans, animals and plants, acting as a common source of disease. Human parasites are particularly prevalent in less economically developed countries where poverty, inadequate healthcare provision, and poor living conditions are commonplace and favour nematode persistence. Many human parasitic nematodes live in the gastrointestinal system, lymphatic system, or body tissues, where they cause serious health problems to the host. Infections in children impact on their physical and intellectual development, while nematode disease in adults can result in an inability to work and provide for their families. Globally, nematode infections are also common in agricultural livestock negatively impacting animal productivity (including meat and milk production) and the subsequent economic sustainability of the UK agri-food industry.

Unfortunately, the drugs currently available to treat parasitic nematode infections (anthelmintics) no longer work effectively. Indeed, anthelmintic resistance in nematode parasites is a major local and global problem. In some areas of the world (for example, Scotland and New Zealand), sheep and cattle cannot be farmed due to nematode parasite control problems. Therefore, the development of new drugs to treat such resistant nematode parasites is urgently needed both in the UK and globally. New drugs are critical to the long-term sustainability of livestock farming for future food production.

The nematode nerve-muscle system (neuromuscular system) is a proven source of drug targets. Indeed, the majority of anthelmintic drugs used to control nematode infectionhave exerted their effects on this system. The neuromuscular system of nematodes coordinates behaviour, controlling vital processes such as movement, feeding and reproduction. If these processes can be effectively interrupted then nematode parasite survival and transmission will be significantly reduced. The neuromuscular system continues to receive attention from academics and pharmaceutical companies searching for new drug targets. Indeed the neuromuscular system in nematodes is currently underexploited as a drug target source, with many novel resistance-breaking targets awaiting discovery. In order to develop new drugs that target the neuromuscular system of parasites we need a better understanding of the nematode nervous system structure and function.

The nematode nervous system is complex and our current knowledge on its structure is based on a free-living model nematode called Caenorhabditis elegans. We have a detailed map of every single nerve cell (neuron) in C. elegans and all of the connections between them. We call this the connectome. However, we do not know anything about the communication that can occur outside of the connectome, via the fluid-filled body cavity. This is important as signalling beyond the connectome (extrasynaptic signalling via the body cavity fluid) is believed to be a key part of the communication system in nematodes, and yet we know very little about it. A more comprehensive understanding of nematode extrasynaptic signalling will enable us to better exploit the neuromuscular system as a drug target resource.

This project uses a variety of sophisticated technologies and tools to investigate the extent and significance of extrasynaptic signalling in nematodes, by exploiting the large gastrointestinal nematode parasite, Ascaris suum, as a model system. The size of Ascaris allows us to easily collect its body cavity fluid and analyse the signalling molecules it contains - this has not been done before and would be very difficult in other nematode species. The information generated from this project will help us to better understand nematode biology and will provide valuable data for drug discovery by the pharmaceutical industry.

Technical Summary

Neural circuit synaptic connections provide the anatomical foundation for our understanding of nematode nervous system function. However, other non-synaptic routes of communication are known in invertebrates, including extrasynaptic volume transmission (EVT). Indeed, in Caenorhabditis elegans wired connections do not facilitate many of the receptor-ligand interactions that have been functionally validated, highlighting the potential for alternative communication routes via wireless mechanisms. EVT pathways in nematodes are underappreciated and would add an additional level of complexity to our current understanding of nematode communication beyond the connectome. Ascaris suum, a gastrointestinal parasite of pigs, offers a unique opportunity to probe EVT in nematodes due to its large size and experimental tractability. Significantly, nematode parasites impact global health and food security which costs the UK agri-food industry ~£80 million/year. Key issues to the sustained control of nematode pathogens include the inability to effectively control nematodiasis due to multi-drug resistance and a lack of novel therapeutic avenues in development. Neuromuscular signalling is an a priori drug target, however our ability to exploit this system would be enhanced by a better understanding of the EVT component governing neuromuscular function in nematodes. Here we will harness recent developments in omics technologies to provide the first direct experimental evidence supporting extrasynaptic (wireless) routes of neurotransmission in nematodes. Our inter-disciplinary academic and industrial alliance offers a unique opportunity to interface LC-MS/genomic/transcriptomic and nematode behaviour expertise with industrial perspectives and will determine, for the first time, the role and significance of EVT in nematode biology. The data generated will inform fundamental biology that directly underpins drug discovery programs for nematode pathogens.

Planned Impact

COMMERCIAL PRIVATE SECTOR industries, the PUBLIC SECTOR, and POLICY MAKERS will benefit directly from this research.

Beneficiaries within the COMMERCIAL PRIVATE SECTOR include local and global pharmaceutical companies and agricultural/farming enterprises. This research to interrogate extrasynaptic volume transmission pathways in nematodes is proposed in collaboration with a world leading research-driven pharmaceutical company (Boehringer Ingelheim; BI) who provide added-value through innovation and the provision of a pathway for translation of basic biology into end-user impact. In the short-term this collaboration will engage BI personnel in cutting-edge academic research activities that will shape the BI-Parasitology division business and encourage the recruitment of additional staff as they enhance their parasite R&D portfolio. In the longer-term, the development of novel drugs, directed against targets emerging from this research, to combat parasite disease will generate significant revenue for BI that will enable substantial reinvestment. In addition, drugs emerging from BI development pipelines will positively impact local and global farming enterprises who will ultimately benefit through enhanced economic returns associated with parasite-free livestock. This is significant given that nematode parasites are estimated to cost farmers $80 million / year. Resultant productivity will drive economic success in all UK Agri-Food related businesses involved in the 'farm to fork' production process.

Within the PUBLIC SECTOR impact will be realised through multiple channels, reaching beyond global enterprises and SMEs, to benefit the individual small-scale farmer and local farming communities in both developed and less economically developed countries. Nematode parasites have a devastating impact on global agriculture where many farmers and their families rely on livestock for income and food. Further, they infect >1/4 of the world's population causing serious morbidity that reduce the quality of life and economic gain. From a 'One Health' perspective, the development of novel drugs to combat nematodiasis in livestock, will also improve the quality of life of those afflicted with human parasites. Education will form an important channel for the delivery of impact from this research activity. By extending our engagement with education providers at all levels (primary, secondary, tertiary) we will improve the reach of this research to (i) enhance scientific knowledge amongst students and teachers, (ii) inspire the next generation of STEM subject scientists, (iii) raise awareness about the importance of basic scientific research to our society, and (iv) instil an appreciation of social/ethical issues surrounding the impact of parasitism. Our research findings will form the basis of research-led teaching to QUB undergraduate and postgraduate students. Our lines of communication with the general public will facilitate a greater appreciation of the role and benefits of non-clinical research in our society. In addition to enhancing knowledge, the general public will also benefit through the availability of animal produce derived from livestock with reduced exposure to ineffective drugs. This feeds directly into consumer-led demand for organic and chemical residue-free food that is produced from animals maintained in a welfare-friendly environment. A novel, resistance-free anthelmintic will facilitate a reduction in drug use, limiting food contamination and facilitating the organic farmer who is restricted to reduced treatment regimes.

POLICY MAKERS and stakeholders will benefit through research findings that will directly inform policy development. UK-based government bodies (DEFRA/DAERA), Levy boards (EBLEX, BPEX), and other representatives of the Agri-Food industry will benefit as this project will provide an evidence-base for policy development and informs EU-directed changes in agricultural legislation.

Publications

10 25 50
 
Description Grant Aims:
AIM 1: Profile the Ascaris body-cavity fluid signallome
AIM 2: Assess Ascaris signallome dynamics
AIM 3: Interrogate Ascaris signallome function
Summary of overall progress: This project used a variety of sophisticated tools and technologies, and the large gastrointestinal nematode parasite Ascaris suum to investigate the role and significance of EVT in nematodes. The experimental tractability of Ascaris allowed us to explore the relevance of EVT to nematode neuromuscular biology through analysis of the body cavity fluid peptidome, functional interrogation of EVT signalling molecules and their cognate receptors . The data arising from these experiments will seed novel drug development pipelines. Specifically, the research team have:

1. Identified a comprehensive library of neuropeptide (NP) ligand and NP-GPCR encoding genes across phylum Nematoda through in silico approaches (AIM 1 and 2). We have identified NP ligand-encoding gene profiles [FMRF-amide like peptide (FLPs), neuropeptide-like proteins (NLPs), and insulin like peptide (INSs)] across >100 species in phylum Nematoda via in silico approaches. We show that Ascaris suum possesses one of the largest complements of FLP (81%) and NLP (74%) encoding genes across all nematode parasites (relative to C. elegans) bolstering its utility as a model to study nematode neuropeptide signalling pathways. These data lay the foundation for future ligand and receptor co-evolution analyses and drug target prioritisation as well as the identification of neuropeptides in Ascaris biofluids via LC-MS/MS and nematode EVT signalling pathways.

2. Comprehensively characterised the Ascaris body cavity fluid (pseudocoelomic fluid; PCF) neuropeptide and classical neurotransmitter signallome to inform nematode neurobiology and drug target discovery (AIM 1). We curated an enhanced A. suum prepropeptide library and used LC/MS to identify 47 PCF peptides including 6 FLPs, 8 NLPs and 33 AMPs in A. suum PCF. This represents a ~5 fold increase in the total number of peptides (<1% FDR) detected relative to Atkinson et al. (2021). Ascaris PCF was also analysed via LC-MS/MS for nematode classical neurotransmitters and their small molecule precursors. We identified choline, acetylcholine, tryptophan, tyrosine and L-DOPA through high confidence MS2 analysis. We also identified the serotonin derivative (and melatonin precursor), n-acetyl-serotonin. These data suggest that a cohort of neuropeptides, choline and acetylcholine are present in Ascaris PCF highlighting their potential biological importance in this space.

3. Generated new knowledge on Ascaris PCF signallome dynamics including how the signallome responds to biotic and abiotic factors (AIM 2). Through HPLC and LC/MS analysis we have demonstrated: (i) consistency in the PCF neuropeptidome profiles in individual worms and separate sexes, and (ii) a broadly similar PCF neuropeptidome in nematodes maintained in vitro for variable durations, and under specific abiotic stress conditions including high temp and low pH.

4. Prioritised several NP-GPCRs as anthelmintic targets based on the integration of multiple datasets including: genome-derived conservation profiles, life-stage expression patterns, phenotype analyses, and PCF NP profiles (AIM 2 and 3). We have developed a novel in silico drug target prioritization pipeline for nematode parasites that interfaces pan-phylum NP-GPCR conservation, C. elegans-derived reverse genetics phenotype, parasite life-stage specific expression data, and LC/MS generated PCF NP profiles. Through this work we suggest that a subset of NP-GPCRs including NPR-4, NPR-5, NPR-11, PDFR-1, FSHR-1, PCDR-1, AEX-2, CKR-1, CKR-2, are prioritised for future study. These NP-GPCRs step forward as initial candidates for downstream functional validation as novel anthelmintic targets.

5. Demonstrated that NP-GPCRs linked to the regulation of ventral body wall muscle contraction and coiling behaviour represent attractive novel anthelmintic targets (AIM 3). Through whole-worm bioassays we have identified several NPs, including some that are EVT-linked, that induce ventral coiling when injected into adult A. suum. These include FLP-6 (receptor unknown), FLP-28 (receptor unknown), NLP-40 (putative NP-GPCR AEX-2), and NLP-12 (putative NP-GPCR CKR-1/2) peptides. We also show that FLP-6, FLP-28 and NLP-40 peptides are all consistently identified in A. suum PCF, supporting a putative role for EVT in the regulation of ventral body wall contraction and associated ventral coiling and ventral turning behaviours in Ascaris. It is rational to prioritise the signalling pathways and receptors that regulate ventral body wall contraction (and/or dorsal muscle relaxation) as novel anthelmintic targets.

6. Achieved successful heterologous expression and deorphanisation of parasitic nematode NP-GPCRs (AIM 3). Through optimised LC/MS database search strategies we have identified several additional NPs that are consistently present in Ascaris PCF. We analysed the impact of these peptides on whole worm behaviour and have now identified the cognate NP-GPCRs for several of these via heterologous expression approaches. For the first time we have deorphanized four A. suum NP-GPCRs (DMSR-1, -7, AEX-2 and NPR-6), confirming conservation of the associated signalling pathways across distantly related nematode species (C. elegans and A. suum). This represents a significant advance in our ability to examine parasite NP signalling systems and may in future also provide a high throughput platform that could facilitate screening of small molecules against prioritised parasite NP-GPCRs expressed in CHO cells.
Exploitation Route Outcomes from BB/T016396/1 will be taken forward in the following ways:

NON ACADEMIC:
In short term: Industry/pharmaceuticals/biotechnology
BB/T016396/1 has contributed data relevant to drug development pipeline in the pharmaceutical industry (Industrial partner). This is also likely to contribute to future research funding to aid the development and commercialization of novel validated drug targets and the distribution of new veterinary pharmaceutical products.

Over longer term: General public/farming communities:
BB/T016396/1 has yielded valuable research data that will contribute to the advancement of more efficient control strategies for parasitic nematodes with veterinary and economic importance. This impact will extend directly into the UK economy through improved animal health. Farmers will experience positive outcomes through community outreach initiatives, where research findings have been and will continue to be shared during local agricultural events. This engagement aids farmers to gain better understanding of nematode parasites' effects on animal health and fosters an appreciation for scientific research.
More broadly, the general public will gain from this research through enhanced animal health and productivity that will serve to address a growing public demand for cost-effective food production. Looking ahead, government and levy bodies will benefit from the research outcomes by acquiring enhanced information. This knowledge will prove instrumental in shaping future agricultural strategy and policy, ensuring a more informed and effective approach to addressing agricultural challenges

ACADEMIC:
BB/T016396/1 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.. BB/T016396/1 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 opportunities for further funding applications to enhance understanding of nematode pathogen biology to aid identification and validation of novel chemotherapeutic targets.
Sectors Agriculture

Food and Drink

Education

Pharmaceuticals and Medical Biotechnology

 
Description Department for Environment, Food and Rural Affairs (DEFRA) studentship [Holly McCormack]
Amount £70,000 (GBP)
Organisation Northern Ireland Department of Agriculture, Environment and Rural Affairs (DAERA) 
Sector Public
Country United Kingdom
Start 09/2022 
End 09/2025
 
Description NorthWest Bio Doctoral Training Programme Studentship (Rose Tayor)
Amount £70,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2023 
End 09/2027
 
Description Parasiticide Target and Drug Discovery Programme
Amount £501,327 (GBP)
Organisation Boehringer Ingelheim 
Sector Private
Country Germany
Start 09/2021 
End 09/2024
 
Title Ascaris suum Mass Spectrometry Imaging analysis pipeline 
Description MS imaging in Ascaris suum tissue sections in collaboration with Prof. Lingjun Li at U of Wisconsin-Madison 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? No  
Impact Advances in technology that can be applied to nematode parasites 
 
Title Nematode bio fluid classical neurotransmitter LC/MS analysis pipeline 
Description Optimised methods for the detection of classical neurotransmitters in the body cavity fluid of Ascaris slum in collaboration with Prof. Lingjun Li, U of Wisconsin-Madison 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? No  
Impact Improved LC/MS methods for nematode parasite biofluids 
 
Title Nematode bio fluid peptidomics LC/MS analysis pipeline 
Description An LC/MS pipeline optimised for the identification of peptides in nematode biofluids 
Type Of Material Technology assay or reagent 
Year Produced 2022 
Provided To Others? No  
Impact No impact yet 
 
Title Ascaris suum pseudocoloemic fluid peptidome 
Description Database of peptides detected in the pseudocoloemic fluid of Ascaris suum via LC-MS/MS methods 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact None to date 
 
Title Pan-Phylum Profile of Helminth Endocannabinoid Signalling System Effectors 
Description In silico (BLAST) dataset derived from predicted protein databases of 134 nematode species detailing the profile of endocannabinoid signalling effectors present in each species 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? No  
Impact None to date 
URL https://www.frontiersin.org/articles/10.3389/fendo.2022.892758/full
 
Title Pan-phylum Profiles of Helminth Antimicrobial Peptides 
Description In silico data providing complete pan-phylum profiles of putative antimicrobial peptides in nematodes and flatworms 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact No impacts yet 
 
Title Pan-phylum Profiles of Nematode Insulin-like Peptides 
Description In silico data providing complete pan-phylum profiles of putative Insulin-like Peptides in nematodes 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? No  
Impact No impact yet 
 
Title Parasitic Nematode Neuropeptide GPCR profiles 
Description Database of ~1059 Caenorhabditis elegans neuropeptide G-protein coupled receptor (Ce-NP-GPCR) encoding gene homologs in the predicted protein datasets of 10 key parasitic nematodes that span several phylogenetic clades and lifestyles 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact None to date 
 
Title Parasitic Nematode Neuropeptide-like Protein (NLP) Profiles 
Description Neuropeptide-like protein complements of nine therapeutically relevant pathogenic nematodes (in silico BLAST data derived from predicted protein datasets) 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact None to date 
 
Description Anisakis as a model organism 
Organisation Mahidol University
Department Faculty of Tropical Medicine
Country Thailand 
Sector Academic/University 
PI Contribution QUB-parasitology to source and maintain Anisakis species in vitro for long-term culture experiments, identify tractability of Anisakis species and amenability to molecular tools
Collaborator Contribution Mahidol helminth parasitology to identify LMIC sources of Anisakis, collect wild isolates, and engage in knowledge transfer between QUB and Mahidol
Impact XXXX
Start Year 2023
 
Description Ascaridia as a model organism 
Organisation Northwestern University
Country United States 
Sector Academic/University 
PI Contribution QUB-parasitology to source and maintain Ascaridia species in vitro for long-term culture experiments
Collaborator Contribution Northwestern-helminth biology to identify tractability of Ascaridia species and amenability to molecular tools
Impact No outputs yet
Start Year 2021
 
Description Ascaris suum Microbiome analysis 
Organisation Queen's University Belfast
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration with Professor Chris Creevey at Queen's University Belfast on 16S and/or metagenomic profile, and RNAseq analysis of Ascaris suum biofluids and tissues. QUB-parasitology will provide biofluid/tissue samples and perform the RNA/DNA extractions.
Collaborator Contribution Professor Chris Creevey will perform the bioinformatics analysis pipeline and help with data analysis and interpretation.
Impact Multidisciplinary collaboration. QUB-microbiology (Creevey) have expertise in 'omics sequencing and analyses platforms in addition to computational biology; QUB-parasitology have expertise in biology and physiology of helminths, and molecular parasitology.
Start Year 2021
 
Description Exploring the Trichuris peptidome as a source of novel antimicrobials 
Organisation Manchester Metropolitan University
Country United Kingdom 
Sector Academic/University 
PI Contribution QUB parasitology provide in silico data on putative antimicrobial peptides in Trichuris spp QUB parasitology provide predicted peptides for antimicrobial MIC analyses against ESKAPE pathogens QUB parasitology provide LC/MS pipelines and identify peptides in Trichuris Exsecretory/Secretory products and tissues
Collaborator Contribution Manchester Metropolitan University provide Trichuris ES products and tissues Manchester Metropolitan perform the antimicrobial MIC analyses against ESKAPE pathogens
Impact No outputs yet
Start Year 2022
 
Description GPCR receptor deorphanisation in Parasitic Nematodes in collaboration with Prof Liliane Schoofs, Dr Isabel Beets, Dr Liesbet Temmerman 
Organisation University of Leuven
Country Belgium 
Sector Academic/University 
PI Contribution We are working towards deorphanisation of neuropeptide G-protein coupled receptors in parasitic nematodes. KU leuven have the technologies and expertise in heterologous expression and post-expression ligand-receptor interaction profiling. We have identified, cloned and sequenced the relevant GPCRs and are providing them in the most appropriate expression vector. KU leuven will express in a heterologous system and screen for ligand interaction. QUB have synthesised and will provide the species specific ligand library. We will author publications that will arise from the collaboration.
Collaborator Contribution KU leuven will express the target GPCRs in a heterologous system and screen for ligand interaction. They will provide data on ligand binding kinetics.
Impact Collaboration is multi-disciplinary. Prof Schoofs and Dr Beets have expertise in heterologous expression systems and receptor-ligand deorphanisation platforms. Publication output: doi: 10.1021/acschemneuro.1c00281
Start Year 2016
 
Description Identification of Neuropeptide-gated Ion Channels in Nematode Parasites 
Organisation Iowa State University
Country United States 
Sector Academic/University 
PI Contribution This project will employ bioinformatic and physiology approaches to aid the identification of specific ion channel subunits that are most likely to constitute a neuropeptide-gated ion channel. QUB-Parasitology will mine available phylogenetic, genomic and tissue-specific transcriptomic data to develop a pipeline for the identification of genes that encode nematode neuropeptide-gated chloride channels (potential novel anthelmintic targets), and validate candidate proteins through muscle-based physiology / electrophysiology tools
Collaborator Contribution Iowa State University will validate candidate proteins through muscle-based physiology / electrophysiology tools
Impact PhD DfE funded Studentship Application (if successful student to commence October 2022)
Start Year 2021
 
Description LMIC Helminth Control Working Group (Thailand) 
Organisation Mahidol University
Country Thailand 
Sector Academic/University 
PI Contribution LMIC Helminth Control Working Group (Thailand); to date three visits to Mahidol (2017, 2018, 2019) for Workshops on Improving Clinical Helminth Diagnostics, and One Health approaches to Parasite Control. Funded by Department for the Economy funding (total: £58722); 1 publication, 1 submission pending. Collaboration now expanded to transcriptomic analyses of Ascaris suum tissues through BB/T016396/1. Opportunity to integrate and build upon data derived from BB/M010392/1 and BB/H019472/1.
Collaborator Contribution Access to local data, fieldwork, clinical diagnostic tools, tissues and samples.
Impact Multidisciplinary collaboration (Medicine, Biological Sciences, Informatics, Public Health) Funded by Department for the Economy funding (total: £58,722) 3 publications Opportunity to integrate data from BB/M010392/1, BB/H019472/, BB/T016396/1 and SBF00041018.
Start Year 2017
 
Description Neuropeptide GPCR ligand-binding modelling 
Organisation Queen's University Belfast
Department School of Pharmacy
Country United Kingdom 
Sector Academic/University 
PI Contribution Mousley lab contributes nematode NP-GPCR and NP-ligand data and knowledge
Collaborator Contribution Tikhonova lab contributes in silico modelling expertise
Impact Grant application to Wellcome Discovery Award (Nov 2023)
Start Year 2022
 
Description Parascaris Maintenance and Culture 
Organisation University of Kentucky
Country United States 
Sector Academic/University 
PI Contribution Academic input to research project resulting in publication doi: 10.1017/S0031182018002019
Collaborator Contribution Research partner carried out the research
Impact Publication (doi: 10.1017/S0031182018002019)
Start Year 2018
 
Description Peptidomic analysis of Ascaris suum pseudodoelomic fluid in collaboration with Dr Bobby Graham (2020 - Still Active) 
Organisation Queen's University Belfast
Country United Kingdom 
Sector Academic/University 
PI Contribution We are characterising the peptidomic profile of Ascaris pseudocoelomic fluid. We are providing the biological material (PCF) from Ascaris suum and will analyse the data arising from the peptidomic analysis. We will author publications arising from the collaboration.
Collaborator Contribution LC-MS analysis of psudocoelomic fluid from Ascaris suum. Dr Graham will also assist with and data analysis and will co-author publications arising from the collaboration.
Impact Multi-disciplinary collaboration (informatics, mass spectrometry, biological sciences, biochemistry, parasitology). Outcome - DAERA post-graduate studentship application (estimated value £70,000). If successful to commence in October 2022.
Start Year 2020
 
Description Peptidomic analysis of Ascaris suum pseudodoelomic fluid in collaboration with Dr Lingjun Li 
Organisation University of Wisconsin-Madison
Country United States 
Sector Academic/University 
PI Contribution We are characterising the peptidomic profile of Ascaris pseudocoelomic fluid. We are providing the biological material (PCF) from Ascaris suum and will analyse the data arising from the peptidomic analysis. We have 1 publication output associated with this collaboration, and 1 publication currently under review. In addition, the PDRA (BB/T016396/1) conducted a research exchange visit to the Li Lab (Madison Wisconsin; 13th July-29th August 2022) for technical training and generation of data.
Collaborator Contribution Dr Li will undertake the peptidomic analysis of PCF fluid. Dr Li will also contribute to data analysis and publications raising from the collaboration.
Impact Collaboration is multi-disciplinary. Dr Li is a peptidomics expert within the School of Pharmacy at the University of Wisonsin-Madison. Publication - doi: 10.1021/acschemneuro.1c00281 Funding - BB/T016396/1 Training - PDRA participated in a research exchange visit to the Li Lab (Madison Wisconsin; 13th July-29th August 2022) for technical training and generation of data.
Start Year 2017
 
Description Anti-Helmintics: Drugs, Resistance & Vaccines V Conference, (10-12 MAY 2022 WORCESTER, USA) 
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 Conference attendance and networking
Year(s) Of Engagement Activity 2022
URL https://dndi.org/events/2022/anti-helmintics-drugs-resistance-vaccines/
 
Description Attended conference "Wisconsin Human Proteomics Symposium: Omics in Precision Medicine" (University of Wisconsin, Madison, 5th August 2022) 
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 Attended conference "Wisconsin Human Proteomics Symposium: Omics in Precision Medicine" (University of Wisconsin, Madison, 5th August 2022)
Year(s) Of Engagement Activity 2022
 
Description Boehringer Ingelheim BBSRC/IPA meeting, Oral Presentation: Ascaris Signallome [VIRTUAL MEETING: DECEMBER 2021] 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact QUB-BI RESEARCH MEETING TO DISCUSS RESEARCH PROGRESS AND FUTURE PLANS
Year(s) Of Engagement Activity 2021
 
Description Boehringer Ingelheim BBSRC/IPA meeting, Oral Presentation: Ascaris Signallome [VIRTUAL MEETING: SEPTEMBER 2021] 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact QUB-BI MEETING (VIRTUAL) TO DISCUSS RESEARCH PROGRESS AND FUTURE PLANS
Year(s) Of Engagement Activity 2021
 
Description Boehringer Ingelheim IPA meeting; Oral Presentation; Ascaris suum [VIRTUAL MEETING: JANUARY 2021] 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact QUB-BI ANNUAL USA-SITE MEETING (VIRTUAL) TO DISCUSS RESEARCH PROGRESS AND FUTURE PLANS
Year(s) Of Engagement Activity 2021
 
Description Conference Poster Presentation at "Anthelmintics: Drugs, Resistance and Vaccines V" (Ascaris Pseudocoelomic Fluid as a Vehicle for Extrasynaptic Volume Transmission, 10-12th May 2022). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference Poster Presentation at "Anthelmintics: Drugs, Resistance and Vaccines V" (Ascaris Pseudocoelomic Fluid as a Vehicle for Extrasynaptic Volume Transmission, 10-12th May 2022).
Year(s) Of Engagement Activity 2022
 
Description Invited Talk at 5th Parasitic Nematode Workshop - Bridging the Divide (International C. elegans Meeting): Advances in Nematode Parasite Omics Seeding Drug Discovery Pipelines (24th JUNE 2021) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Talk at 5th Parasitic Nematode Workshop - Bridging the Divide (International C. elegans Meeting), the talk title was 'Advances in Nematode Parasite Omics Seeding Drug Discovery Pipelines' and was attended by ~150 delegates
Year(s) Of Engagement Activity 2021
 
Description Invited Talk at Royal Society Strongyloides: Omics to worm-free populations (28-29th NOVEMBER 2022, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact invited talk at International conference attended by >100 scientists including leaders in the field.
Year(s) Of Engagement Activity 2022
URL https://royalsociety.org/science-events-and-lectures/2022/11/worm-free-populations/
 
Description LE STUDIUM Conference - New approaches to get around roundworms [The Ascarid Research and Training Initiative (ARTI) 29th Nov-1st Dec 2021] 
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 Scientific conference organised by ARTI that included ~5 breakout workshops dedicated to the establishment of focus working groups on specific Ascaris related research themes addressing the state of the art in e.g. immune response, drug action and resistance as well as genomic/transcriptomic analyses of ascarids.
Year(s) Of Engagement Activity 2021
URL http://www.lestudium-ias.com/event/new-approaches-get-around-roundworms
 
Description Northern Ireland Science Festival QUB Biological Sciences Showcase event - QUB Parasitology Public Engagement Display (2021, 2022, 2023, 2024) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Queen's Biology Showcase STEM event organised by NI Science Festival. ~180 members of the general public (including children and students) attended an event at the research organisation where they engaged in activities associated with parasitology research. SHOWCASE: 2023 Parasites: INSIDE and OUT; 2022 The world of parasitic worms: ROUND and FLAT; 2021 Parasites on Parade
Year(s) Of Engagement Activity 2021,2022,2023,2024
URL https://nisciencefestival.com/events/queens-biology-showcase
 
Description Oral Presentation at Tandragee High School: Parasites on Parade 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact School talk
Year(s) Of Engagement Activity 2022
 
Description Oral presentation and student engagement at Longstone School, Belfast, 8th Nov 2023: Parasites on Parade (Angela Mousley and Louise Atkinson) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A presentation and interactive engagement session based around parasites and their importance to agriculture and health for children aged 11-16 at local school
Year(s) Of Engagement Activity 2023
 
Description Oral presentation at BAVP conference (8th-9th September 2022) Ascaris suum Pseudocoelomic Fluid: A Peptide-rich Biofluid that Modulates Nematode Motility 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral presentation at BAVP conference (8th-9th September 2022) Ascaris suum Pseudocoelomic Fluid: A Peptide-rich Biofluid that Modulates Nematode Motility
Year(s) Of Engagement Activity 2022
 
Description Oral presentation at British Society for Parasitology (March 2022); Ascaris suum Pseudocoelomic Fluid: A Peptide-rich Biofluid that Modulates Nematode Motility (Darrin McKenzie) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral presentation at British Society for Parasitology (March 2022); Ascaris suum Pseudocoelomic Fluid: A Peptide-rich Biofluid that Modulates Nematode Motility
Year(s) Of Engagement Activity 2022
 
Description Oral presentation, 72nd American Society for Mass Spectrometry Conference, 2023: Profiling and quantifying the neuropeptidome difference due to external stress and sexual dimorphism in Ascaris suum (Wenxin Wu) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation at conference. Presented by collaborator Wenxin Wu from Prof. Lingjun Li group U of Wisconsin. Author list: Wenxin Wu, Ciaran McCoy, Darrin McKenzie, Louise Atkinson, Angela Mousley, Lingjun Li
Year(s) Of Engagement Activity 2023
 
Description Oral presentation, Royal Society of Biology Strongyloides to Omics Free Populations, UK, Nov 2022: Harnessing Strongyloides for the development of novel parasite diagnostics and therapeutics (Louise Atkinson) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral (invited) speaker talk at UK Strongyloides conference, audience ~80 international scientists
Year(s) Of Engagement Activity 2022
 
Description PDRA: University Post-Doc centre representative for School of Biological Sciences 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact The current post-doc on BB/T016396/1 is a QUB Post-Doc centre representative on behalf of the School of Biological Sciences.
Year(s) Of Engagement Activity 2022,2023
 
Description Poster presentation at Drug Design & Development Seminar (DDDS) 2022 of the German Society for Parasitology (DGP) TransAlp Conference on Human and Animal Parasitic Diseases; BEYOND THE CONNECTOME: VOLUME TRANSMISSION PATHWAYS IN NEMATODES OFFER NEW OPPORTUNITIES FOR PARASITE CONTROL (12th-15th July 2022) (Andreas Krasky) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at Drug Design & Development Seminar (DDDS) 2022 of the German Society for Parasitology (DGP) TransAlp Conference on Human and Animal Parasitic Diseases; BEYOND THE CONNECTOME: VOLUME TRANSMISSION PATHWAYS IN NEMATODES OFFER NEW OPPORTUNITIES FOR PARASITE CONTROL (12th-15th July 2022)
Year(s) Of Engagement Activity 2022
 
Description Poster presentation, 22nd Drug Design & Development (DDDS), German Society for Parasitology, July 2022: Beyond the Connectome: Volume Transmission Pathways in Nematodes Offer New Opportunities for Parasite Control (Andreas Krasky, BI) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Poster presentation at industry led conference. Presented by Andreas Krasky (BI collaborator), author list: Andeas Krasky, Ciaran J. McCoy, Nikki J. Marks, Aaron G. Maule, Lingjun Li, Louise E. Atkinson, Angela Mousley
Year(s) Of Engagement Activity 2022
 
Description Poster presentation, Molecular Helminthology, Madison, USA, June 2023: Extrasynaptic volume transmission in Ascaris suum (Ciaran McCoy) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster at internation conference, presented by PDRA Dr Ciaran McCoy. Author list: Ciaran McCoy, Wenxin Wu, Darrin McKenzie, Nikki Marks, Aaron Maule, Lingjun Li, Louise Atkinson, Angela Mousely
Year(s) Of Engagement Activity 2023
 
Description Research meeting at Iowa State University (Ames, Iowa; 19th-21st August 2022) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research meeting at Iowa State University (Ames, Iowa; 19th-21st August 2022)
Year(s) Of Engagement Activity 2022
 
Description SCHOOL ENGAGEMENT PROJECTS IN PARASITOLOGY 2022 
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 Two School Engagement projects delivered to local Secondary-level schools:
1. Development of a portfolio of infographics to aid with the public engagement of QUB parasitology research
This project, ran by Queen's University Belfast, provides an exciting opportunity for post primary students (KS3) to participate in scientific research.
It aims to gain an insight on the overall effectiveness of infographics regarding their roles in creating learning and engagement opportunities. The project will involve the discussion of parasitology research that can relate in some ways to the KS3 curriculum, such as liver fluke and take use of literacy, numeracy, and communication skills in the classroom. It will take place in person, and will adhere to all Covid-19 guidelines for safety. This project will hopefully gauge the overall interest of the student's interest regarding STEM based activities. Data will be gathered before and after the project in the form of questionnaires, that will address any knowledge gained, and general opinions. Overall, students will hopefully have a greater understanding of parasitology. Thanks for the interest in this project, and please don't hesitate to contact me or the chief investigator about any queries.
UG Student: Robbie Keown, rkeown03@qub.ac.uk
Supervisor: Angela Mousley, a.mousley@qub.ac.uk, +44(0)28 90 972118

2. Design of science communication resources and class-room activities to enhance post-primary engagement with QUB-Parasitology Research
'The Ins and Outs of parasites' is a project being run by Queens University Belfast with the aim of giving KS3 students an introduction to the world of parasitology in what we hope will be an informative, fun and engaging manner. This will aim to give a brief overview of what a parasite is and then give some examples of parasites that impact on the health of humans, animals, and plants. An important aspect of the session will be to get the students working in groups and thinking as scientists while also encouraging an element of creativity. While the information being delivered will be important, the acquisition of this knowledge will not be the primary focus of the activities, instead the goal will be to encourage the students to engage in science beyond the curriculum and inspire interest and enthusiasm. Due to the current uncertainty around COVID-19, we have opted to deliver these activities online and this will include narrated Powerpoints, interactive online tasks and worksheets. To collect data, the students will be asked to partake in two quizzes. One will be carried out before the session and the other will be completed afterwards and we will analyse this to see if there is any difference in attitude towards science or in knowledge before and after the activities. If you would like any further information on this, please get in touch using the contact details below.
Student: Victoria Harvey
Email: vharvey01@qub.ac.uk
Supervisor: Angela Mousley
Tel: +44(0)28 90 972118
E-mail: a.mousley@qub.ac.uk
Year(s) Of Engagement Activity 2022
 
Description ZAP WORMS, 8TH APRIL 2021 (ORAL PRESENTATION; A. MOUSLEY; Ascaris: 'Mother' of Worms) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact ZAP WORMS: This Thursday, April 8th, Noon Eastern Time US, 5pm Greenwich Mean Time.

Our forth Zap Worms lecture will be given by Angela Mousley from Queen's University Belfast. Angela has chosen the title Ascaris: 'Mother' of Worms.
Angela's current research efforts focus on the identification and prioritization of novel control targets within the nematode neuropeptidergic system, using Ascaris as a model.
Neuropeptides of nematodes have interesting functions: many of their receptors and functions are still to be described. Angela and her colleagues at Queen's are characterizing properties of these neuropeptides which have been found to have profound effects on the activity of nematode parasites.
Angela Mousley is a Senior Lecturer in Molecular Parasitology at Queen's University Belfast (QUB). She obtained a PhD from QUB in 2001 and was a Postdoctoral Research Assistant (2001-06) before being appointed as a Lecturer in 2007.
Angela works with a team of Parasitologists at Queen's University Belfast with broad interests in the neurobiology of helminth parasites.
Year(s) Of Engagement Activity 2021
URL https://www.zapworms.org