ASCARIS SUUM, A NEW FUNCTIONAL GENOMICS PLATFORM FOR NEMATODE PARASITES
Lead Research Organisation:
Queen's University Belfast
Department Name: Sch of Biological Sciences
Abstract
Nematodes (roundworms) are members of the Phylum Nematoda. There are >25,000 species of nematodes and they are outnumbered only by the Arthropods. Their success is due to their ability to occupy a diverse range of habitats. They can either be free-living or parasites of humans, animals and plants. Nematode parasites are a common source of human disease where 1 in 4 people carry at least one nematode species. Human parasitic diseases are mainly restricted to the developing world where poverty, inadequate health care provision, and poor living conditions favour their survival. Some of the most prevalent human nematode parasites live in the gasterointestinal (GI) system feeding on human tissue, blood and gut contents. For example, Ascaris lumbricoides is one of the largest GI nematodes and can cause serious health problems associated with intestinal blockage and impaired growth, especially in children. In livestock, nematode parasites can be a significant problem as they impact not only on the health and well-being of the animal but also on the productivity and subsequent profitability of the farming industry. Haemonchus contortus and Teladorsagia circumcincta are the most pathogenic nematodes of sheep and goats. They are blood-feeders and heavy infections can lead to severe anaemia and animal death. Nematodes are also problematic to the crop industry. They can infect food crops such as tomatoes and potatoes or utility grasses including football pitches or golf courses. Meloidogyne spp are a particular problem because they infect a wide range of plant hosts. They impair plant health by setting up feeding sites in the plant root, removing nutrients needed for plant growth.
Unfortunately the drugs that are available to treat parasitic nematode infections no longer work effectively or are environmentally toxic. We cannot continue to treat nematode infections with the current range of drugs and we must now actively seek new drug targets and develop novel drugs. This is particularly important to the UK as we have to ensure the sustainability of livestock farming for future food production.
This project aims to uncover novel drug targets for the treatment of nematode parasites of livestock. In this project we will collaborate with an animal-health pharmaceutical company to accelerate the chance of identifying a novel drug target at which new drugs could be directed. This approach will make use of scientific research skills and the expertise of the pharmaceutical industry in drug discovery. In order to find new drug targets for nematode parasites, we must first identify proteins that are important to nematode biology and survival. Recently there has been an increase in the availability of gene sequences for a number of important parasitic nematodes, like those described above. We will search through these sequences and find those which code for protein targets which may be essential to parasite survival. We will select sequences that are found in multiple parasites so that we can identify a drug target which could be used to treat multiple nematode diseases. We will then use a technique called RNA interference (RNAi) which allows us to switch off genes in the parasitic nematode to find out their function. For example, if we switch off a gene and the nematode dies or stops moving/feeding/reproducing then we have identified a good drug target candidate as the nematode can no longer infect or remain in its host. We will perform RNAi in a model nematode parasite (Ascaris suum) that we can easily collect from pig intestines at local abattoirs and maintain in the lab. Once we have switched off the target genes, we will determine the impact to the parasite by examining how they survive, behave, move, reproduce, and respond to stimulants. We will then select the five 'best' targets, based on their impact to nematode biology, and deliver these to the pharmaceutical industry who will develop drugs against them.
Unfortunately the drugs that are available to treat parasitic nematode infections no longer work effectively or are environmentally toxic. We cannot continue to treat nematode infections with the current range of drugs and we must now actively seek new drug targets and develop novel drugs. This is particularly important to the UK as we have to ensure the sustainability of livestock farming for future food production.
This project aims to uncover novel drug targets for the treatment of nematode parasites of livestock. In this project we will collaborate with an animal-health pharmaceutical company to accelerate the chance of identifying a novel drug target at which new drugs could be directed. This approach will make use of scientific research skills and the expertise of the pharmaceutical industry in drug discovery. In order to find new drug targets for nematode parasites, we must first identify proteins that are important to nematode biology and survival. Recently there has been an increase in the availability of gene sequences for a number of important parasitic nematodes, like those described above. We will search through these sequences and find those which code for protein targets which may be essential to parasite survival. We will select sequences that are found in multiple parasites so that we can identify a drug target which could be used to treat multiple nematode diseases. We will then use a technique called RNA interference (RNAi) which allows us to switch off genes in the parasitic nematode to find out their function. For example, if we switch off a gene and the nematode dies or stops moving/feeding/reproducing then we have identified a good drug target candidate as the nematode can no longer infect or remain in its host. We will perform RNAi in a model nematode parasite (Ascaris suum) that we can easily collect from pig intestines at local abattoirs and maintain in the lab. Once we have switched off the target genes, we will determine the impact to the parasite by examining how they survive, behave, move, reproduce, and respond to stimulants. We will then select the five 'best' targets, based on their impact to nematode biology, and deliver these to the pharmaceutical industry who will develop drugs against them.
Technical Summary
Nematode parasites impose a significant burden on human/animal health and global food security. The agricultural impact of nematodiasis in the UK is ~£80 million/year, mainly attributed to animal death, morbidity, reduced productivity and reproductive impairment. Traditionally chemotherapeutics have been the foundation of nematode parasite control, but decreasing utility / treatment failures have exposed the rapid development of drug resistance, including multi-drug resistance such that current control options are not sustainable. As a result, novel chemotherapeutics are critical. In this study we will employ both contemporary and traditional approaches to identify and validate novel drug target candidates for exploitation by our industrial partner. Our target-identification strategy will be directed by the recent progress in parasitic nematode genomics/ transcriptomics and will score targets based on their conservation across the phylum, known druggability in other systems, key role in nematode biology and/or survival, and expression in therapeutically relevant lifecycle stages/tissues. Our approaches to functional validation combine two unique attributes offered by this industrial-partnership collaboration: we will use our newly developed adult A. suum RNA interference (RNAi) platform to investigate target function/importance to parasite biology; uniquely, we will interface these reverse genetic approaches with privileged access to the Merial/Sanofi chemical library, which will provide powerful tools to help steer early target prioritisation and to probe functional importance. The combination of both of these tools will provide a powerful and unique approach to animal parasite drug target validation. These efforts will provide the first target validation platform for an animal parasitic nematode and will deliver five functionally-validated drug target candidates for industrial exploitation.
Planned Impact
A. Commercial Private Sector
1. Pharma/Biotech will benefit through economic rewards associated with the provision of a new anthelmintic to a keen market. Our industrial partner (Merial) is committed to developing validated drug targets emerging from this project and exploiting these as screening tools for anthelmintic discovery. This project will also optimise a reverse genetics platform for validation of drug targets in nematode parasites, which will be available for exploitation by other pharma/biotech industries. Additional novel targets arising from this project, which are not of primary interest to Merial, will be available for validation by other industries. This is relevant to those developing treatments for both animal and human nematodiasis, and could provide opportunities for new jobs in the research/development/production pipeline.
2. Local and global farming enterprises will benefit through enhanced economic returns associated with healthier livestock that are more productive. The total income from farming in the UK was £4.7 billion in 2012 facilitating the employment of 481,000 personnel. On a global scale, nematode parasites are estimated to cost farmers $80 million / year. As a direct result of this project, livestock producers will receive economic gain through more effective drugs that are free from resistance. Novel anthelmintics will permit reduced drug treatments, and will enhance animal health, welfare and productivity. Increased productivity will drive economic success in all businesses involved in the 'farm to fork' production process, bolstering the competitiveness of the UK Agri-Food Industry.
B. Policy Makers
1. Stakeholders and policy makers will benefit through research-evidence that will inform policy development:: UK-based government bodies (DEFRA, DARD), 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 addresses EU-directed changes in agricultural legislation, e.g. the need for rapid drug-intervention to facilitate 'Sustainable Intensification'.
C. Public Sector
1. Farming communities in developing countries will benefit through enhanced quality of life: Nematode parasites have a devastating impact on agriculture in developing countries 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. The goal of this project is the development of novel drugs for the treatment of nematode pathogens in livestock, which has the potential to improve quality of life through enhanced economic gain. Moreover the development of novel drugs for veterinary parasites which can be repurposed for use in humans will improve the health, well-being, and quality of life of those afflicted with nematodiasis.
2. Educational sector will benefit through greater understanding of the local and global significance of nematode pathogens: Local schools will benefit from this research by educating students and teachers about nematode biology, and through raised awareness of the importance of research in our society. In addition, research findings will form the basis of research-led teaching to university students at QUB. The host-institute will benefit through an enhanced research profile.
3. General public will benefit through job-creation and opportunity to promote sustainable prosperity: There is a growing demand from the consumer for organic and chemical residue-reduced food that is produced cost-effectively from animals maintained in a welfare-friendly environment. A novel, resistance-free anthelmintic will facilitate a reduction in drug use, therefore limiting food contamination and facilitating the organic farmer who is restricted to reduced treatment regimes. Also, the environmental impact associated with intensive drug use will be reduced.
1. Pharma/Biotech will benefit through economic rewards associated with the provision of a new anthelmintic to a keen market. Our industrial partner (Merial) is committed to developing validated drug targets emerging from this project and exploiting these as screening tools for anthelmintic discovery. This project will also optimise a reverse genetics platform for validation of drug targets in nematode parasites, which will be available for exploitation by other pharma/biotech industries. Additional novel targets arising from this project, which are not of primary interest to Merial, will be available for validation by other industries. This is relevant to those developing treatments for both animal and human nematodiasis, and could provide opportunities for new jobs in the research/development/production pipeline.
2. Local and global farming enterprises will benefit through enhanced economic returns associated with healthier livestock that are more productive. The total income from farming in the UK was £4.7 billion in 2012 facilitating the employment of 481,000 personnel. On a global scale, nematode parasites are estimated to cost farmers $80 million / year. As a direct result of this project, livestock producers will receive economic gain through more effective drugs that are free from resistance. Novel anthelmintics will permit reduced drug treatments, and will enhance animal health, welfare and productivity. Increased productivity will drive economic success in all businesses involved in the 'farm to fork' production process, bolstering the competitiveness of the UK Agri-Food Industry.
B. Policy Makers
1. Stakeholders and policy makers will benefit through research-evidence that will inform policy development:: UK-based government bodies (DEFRA, DARD), 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 addresses EU-directed changes in agricultural legislation, e.g. the need for rapid drug-intervention to facilitate 'Sustainable Intensification'.
C. Public Sector
1. Farming communities in developing countries will benefit through enhanced quality of life: Nematode parasites have a devastating impact on agriculture in developing countries 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. The goal of this project is the development of novel drugs for the treatment of nematode pathogens in livestock, which has the potential to improve quality of life through enhanced economic gain. Moreover the development of novel drugs for veterinary parasites which can be repurposed for use in humans will improve the health, well-being, and quality of life of those afflicted with nematodiasis.
2. Educational sector will benefit through greater understanding of the local and global significance of nematode pathogens: Local schools will benefit from this research by educating students and teachers about nematode biology, and through raised awareness of the importance of research in our society. In addition, research findings will form the basis of research-led teaching to university students at QUB. The host-institute will benefit through an enhanced research profile.
3. General public will benefit through job-creation and opportunity to promote sustainable prosperity: There is a growing demand from the consumer for organic and chemical residue-reduced food that is produced cost-effectively from animals maintained in a welfare-friendly environment. A novel, resistance-free anthelmintic will facilitate a reduction in drug use, therefore limiting food contamination and facilitating the organic farmer who is restricted to reduced treatment regimes. Also, the environmental impact associated with intensive drug use will be reduced.
Organisations
- Queen's University Belfast (Lead Research Organisation)
- Mahidol University (Collaboration)
- University of Wisconsin-Madison (Collaboration)
- MANCHESTER METROPOLITAN UNIVERSITY (Collaboration)
- Washington University in St. Louis (Collaboration)
- University of Kentucky (Collaboration)
- QUEEN'S UNIVERSITY BELFAST (Collaboration)
- University of Leuven (Collaboration)
- Boehringer Ingelheim (United Kingdom) (Project Partner)
Publications
Adisakwattana P
(2020)
Clinical helminthiases in Thailand border regions show elevated prevalence levels using qPCR diagnostics combined with traditional microscopic methods
in Parasites & Vectors
Atkinson L
(2021)
Ascaris suum Informs Extrasynaptic Volume Transmission in Nematodes
in ACS Chemical Neuroscience
Atkinson LE
(2021)
Phylum-Spanning Neuropeptide GPCR Identification and Prioritization: Shaping Drug Target Discovery Pipelines for Nematode Parasite Control.
in Frontiers in endocrinology
Atkinson LE
(2016)
Unraveling flp-11/flp-32 dichotomy in nematodes.
in International journal for parasitology
Cadd L
(2022)
The Strongyloides bioassay toolbox: A unique opportunity to accelerate functional biology for nematode parasites
in Molecular and Biochemical Parasitology
Crooks BA
(2022)
Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery.
in Frontiers in endocrinology
DeLaney K
(2018)
New techniques, applications and perspectives in neuropeptide research.
in The Journal of experimental biology
Gobert GN
(2022)
Clinical helminth infections alter host gut and saliva microbiota.
in PLoS neglected tropical diseases
McCoy CJ
(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.
in International journal for parasitology
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 | Summary of overall progress: 1. We have identified orthologs of 152 NP-GPCRs in parasitic nematodes [AIM 2] Using Hidden Markov Models (HMM) in the predicted protein datasets of 10 key nematode parasites (including key pathogens: Dirofilaria immitis, Haemonchus contortus and A. suum), we found that: (i) parasitic nematodes have a reduced complement of C. elegans NP-GPCRs; (ii) several NP-GPCRs are conserved across the parasitic nematodes. 2. We have developed a prioritisation pipeline for NP-GPCRs [AIM 2 and 3] We have designed a decision matrix for prioritisation of putative NP-GPCR drug targets. This utilises in silico, functional and expression data to prioritize NP-GPCRs based on their perceived importance to nematode biology in therapeutically relevant life-stages and their appeal as novel drug targets. ?Level 1 Prioritization: Pan-phylum conservation of NP-GPCRs Based on HMM pan-phylum NP-GPCR identification several GPCRs have been prioritized: gnrr-1, ckr-2, frpr-19, C01F1.4, F59D12.1, pdfr-1, seb-3, daf-38, dmsr-2, dmsr-8, T11F9.1, H09F14.1. ?Level 2 Prioritization: Aberrant phenotype Based on C. elegans phenotype data (knockout/RNAi) several GPCRs have been prioritized: npr-5, - 29, ckr-1, Y40C5A.4, fshr-1, npr-1, -4, -11, -12, -13, daf-38, dmsr-2, dmsr-4, fshr-1, F59D12.1, and pdfr-1. ?Level 3 Prioritization: Expression analyses of NP-GPCRs in distinct nematode life-stages Based on life-stage specific transcriptomic datasets for six of the 10 parasitic nematode species included in the neuropeptide GPCR identification we have prioritised GPCRs based on their expression in all life-stages or therapeutically relevant life-stages of key parasites. NP-GPCRs emerging from the prioritization pipeline (pdfr-1, F59D12.1, npr-29, ckr-1, ckr-2 and frpr-19. pdfr-1 and F59D12.1) are common to all levels of prioritisation and have been passed to the industrial collaborator as a key deliverable. 3. Through in silico prediction we have developed an approach for matching NP-GPCRs with their cognate ligands [Aim 2 and 3] Through genome and transcriptome level analyses we have identified a cohort of 10 NP-GPCRs (npr- 4, -5, C01F1.4, ckr-2, dmsr-2, F59D12.1, frpr-1, gnrr-1, seb-3, pdfr-1) and 8 ligands (flp-1, -14, -18, nlp-12, -36, -47, -49 and pdf-1) that are conserved across the phylum Nematoda (109 species). 4. We have generated a novel tissue-specific platform for NP-GPCR deorphanisation and validation [AIM 1 and 2] Tissue-specific differential expression analysis of NP-GPCRs and neuropeptide ligands on two specific regions of the A. suum reproductive apparatus (ovijector and bodywall) revealed restricted groups of putative NP-GPCRs expressed on the ovijector, and neuropeptide ligands expressed in neuronal cells innervating the ovijector [FMRFamide-like peptides (flps) and neuropeptide-like proteins (nlps)]. These NP-GPCRs and neuropeptide ligands represent putative receptor-ligand interactions and these data allow validation of the in silico predictions outlined above. 5. We have optimised an Ascaris suum 'ex vivo' RNAi/bioassay for NP-GPCR deorphanisation [AIM 1 and 3]. Our tissue-specific RNAseq data (outlined in 3.) suggests that multiple neuropeptide and NP-GPCR genes are expressed in both ovijector and gonopore tissues. We optimised tissue-specific gene silencing in the ovijector tissue using multiple RNAi delivery approaches: (i) dsRNA injection into the pseudoceolomic cavity of adult female worms and (ii) soaking dissected ovijector tissue in dsRNA. We confirmed successful knockdown of a number of NP-GPCRs including As-npr-4 and -5 in ovijector tissue at 72 hours post-dsRNA injection. These data represent the first report of successful (i) tissue- specific RNAi, and (ii) NP-GPCR gene knockdown in nematodes. 6. We have identified the Ascaris suum Pseudocoelomic fluid (PCF) as a vehicle for extrasynaptic transmission of neuropeptides We determined the presence of neuropeptides in A. suum PCF to investigate other, non-synaptic routes of GPCR-ligand interaction [AIM 2]. We established a collaboration with Dr Lingjun Li (UW-Madison, USA), an expert in the detection of neuropeptides in crab haemolymph, to perform highly sensitive mass-spectrometry based peptidomic analyses of the A. suum PCF. PCF bathes the A. suum ovijector tissue and may represent an unexplored vehicle for neuropeptide signaling. We have identified 10 high-confidence neuropeptides in the body cavity fluid of Ascaris including FLPs and NLPs, in addition to a number of anti-microbial peptides. This is the first neuropeptidomics profile of PCF from a nematode and is the first indication that extrasynaptic transmission may be an integral part of the functional connectome in nematodes. These data provide an additional layer of complexity to the ligand-receptor matching pipelines that we are currently employing and will further support novel target discovery. |
Exploitation Route | ACADEMIC: 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, initially through PhD studentships, to continue the identification and validation of novel chemotherapeutic targets for nematode parasites. |
Sectors | Agriculture Food and Drink Education Pharmaceuticals and Medical Biotechnology |
Description | Outcomes from BB/MO10392/1 have been taken forward in the following ways: Pharmaceutical Industry: Research data generated through BB/MO10392/1 have contributed to a further BBSRC application [Responsive mode IPA application (BB/T016396/1); submitted October 2019] involving the pharmaceutical industry (Boehringer Ingelheim as the industrial partner). This application was successful and commenced in January 2021 (BB/T016396/1). This project will further aid the development and commercialization of novel validated drug targets and the distribution of novel veterinary pharmaceutical products in the future. This will also build on the existing collaboration with Boehringer Ingelheim to translate basic biology to therapeutics that will provide successful health solutions for livestock. General public/farming communities: To date, farmers have benefitted from this research via community outreach activities where our research data has been, and will continue to be, communicated through attendance and participated in local agricultural events (e.g. attendance at local Agricultural Show, interaction with farmers, contribution to funding applications for local 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. It is anticipated that this research will contribute to the development of a new parasiticide for control of nematode parasites of livestock (drug development timeline = 8-10 years). Novel putative targets have been forwarded to the industrial partner. The development of more effective control strategies for parasitic nematodes of veterinary importance will directly benefit farmers through enhanced animal health and economic value. |
First Year Of Impact | 2021 |
Sector | Agriculture, Food and Drink,Education,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal |
Description | Northern Ireland Pig Health Technical Group recommendation for EU Exceptional Adjustment Aid |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Beyond the Connectome: Unravelling Neuropeptide Signalling in Parasitic Nematodes to Inform Drug Discovery Pipelines |
Amount | £458,893 (GBP) |
Funding ID | BB/T016396/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2021 |
End | 06/2023 |
Description | Boehringer Ingelheim IPA Research Award (as part of BB/T016396/1; £ 66,000; 2021-2024) |
Amount | £66,000 (GBP) |
Organisation | Boehringer Ingelheim |
Sector | Private |
Country | Germany |
Start | 01/2021 |
End | 12/2023 |
Description | Department for Employment and Learning PhD studentship [Fiona McKay] |
Amount | £70,000 (GBP) |
Organisation | Government of Northern Ireland |
Department | Department for Employment and Learning Northern Ireland (DELNI) |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | Department for Environment, Food and Rural Affairs (DEFRA) studentship [Darrin McKenzie] |
Amount | £70,000 (GBP) |
Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
Sector | Public |
Country | United Kingdom |
Start | 09/2019 |
End | 09/2022 |
Description | Department for the Economy PhD studentship [Sorcha Donnelly] |
Amount | £70,000 (GBP) |
Organisation | Department for the Economy, Northern Ireland |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 09/2020 |
Description | Identification of Parasite Derived Antibacterial Agents to Tackle Emerging Antimicrobial Resistance and Reduce Antibiotic Use in Livestock [Allister Irvine] |
Amount | £70,000 (GBP) |
Organisation | Government of Northern Ireland |
Department | Department of Agriculture, Environment and Rural Affairs |
Sector | Public |
Country | United Kingdom |
Start | 09/2018 |
End | 08/2021 |
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 | Ascaris suum pseudocoelomic fluid peptidomics datasets |
Description | These datasets represent the peptides expressed in Ascaris suum pseudocoelomic fluid |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | No |
Impact | These datasets can be used to determine the peptides that are released extrasynaptically via volume transmission. In addition, these data are available to map to the predicted protein dataset in Ascaris suum. |
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 | Ascaris suum tissue specific RNAseq datasets |
Description | These datasets represent the genes expressed in distinct tissues of the pig roundworm parasite Ascaris suum. |
Type Of Material | Database/Collection of data |
Year Produced | 2016 |
Provided To Others? | No |
Impact | These datasets can be used for the differential expression analysis of any of the 18,000 genes present in A. suum. This enables the elucidation of fundamental biological pathways present in each tissue type and can infer the importance of specific genes and/or pathways to a tissue/organ essential to the parasite for reproduction and survival. |
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 | 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 | 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 | 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 | RNAseq Analysis of Ascaris suum ovijector and gonopore tissue |
Organisation | Washington University in St Louis |
Country | United States |
Sector | Academic/University |
PI Contribution | Collaboration with Makedonka Mitreva at McDonnell Genome Institute (Washington University at St Louis) on RNAseq analysis of Ascaris suum ovijector and gonopore tissue. QUB provided the RNAseq datasets to the Mitreva group for further analysis. |
Collaborator Contribution | Ongoing collaboration. Partners (Mitreva group) analysing RNAseq data |
Impact | Collaboration ongoing |
Start Year | 2016 |
Description | Anthelmintics from Discovery to Resistance III (ORAL PRESENTATION L ATKINSON, FLORIDA, 30th JANUARY-2nd FEBRUARY: FLP-18 modulates reproductive function in Ascaris suum via extrasynaptic volume transmission? |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Our understanding of nematode nervous system function is founded on neural circuit synaptic interactions. However, other routes of non-synaptic communication are known in invertebrates including extrasynaptic (wireless) volume transmission (EVT), which enables close- or long-range communication where synaptic connections are absent. EVT is thought to be involved in biogenic amine signaling in Caenorhabditis elegans but has not yet been demonstrated in parasitic nematodes or for neuropeptide transmission. Neuropeptide signaling governs many important nematode functions and behaviors. The FMRFamide like peptides (FLPs; PGVLRFamides) encoded on flp-18 are expressed in multiple head neurons of Ascaris suum and have been implicated in locomotion, feeding and reproductive function via whole worm, pharyngeal and ovijector tissue bioassays. Although flp-18 encoded peptides are potent stimulators of the ovijector, they are expressed in head neurons that are anatomically distant from, and have no known synaptic connections to, the ovijector. Tissue specific RNA-Seq analysis reported here demonstrates that neurons innervating ovijector tissue do not express flp-18, and that the putative cognate FLP-18 G-protein coupled receptors (GPCRs) npr-4 and npr-5 are expressed in ovijector tissue. To investigate non-synaptic modes of FLP-18 signaling in A. suum we undertook a peptidomics analysis of the A. suum pseudocoelomic fluid (PCF), which bathes the nematode reproductive organs, including the ovijector. These studies identified multiple FLP-18 peptides in the circulating PCF of all nematodes examined (n=12). These data support the hypothesis that FLP-18 peptides modulate A. suum reproductive function non-synaptically via EVT. Establishing the role of non-synaptic (wireless) routes of neurosignaling in parasitic nematodes and their integration into a functional connectome provides an additional layer of complexity to the ligand-receptor matching processes that support new drug discovery programs. |
Year(s) Of Engagement Activity | 2018 |
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 | 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 | BALMORAL SHOW INTERACTIVE DISPLAY 2019 |
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 | Participation in the Balmoral Show 2019. Display and public engagement on parasites of importance to agriculture in Northern Ireland, sparked discussion and awareness with the general public. |
Year(s) Of Engagement Activity | 2019 |
Description | BAVP conference (8th-9th September 2022) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Participant in British Association for Veterinary Parasitology (BAVP) conference (8th-9th September 2022) |
Year(s) Of Engagement Activity | 2022 |
Description | Boehringer Ingelheim IPA meeting; Oral Presentation; Ascaris suum [BI, ATHENS, APRIL 2019] |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | QUB-BI ANNUAL USA-SITE MEETING TO DISCUSS RESEARCH PROGRESS AND FUTURE PLANS |
Year(s) Of Engagement Activity | 2019 |
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 | Boehringer Ingelheim Industrial Collaborator Meeting, Oral Presentation - Ascaris suum research [BI, ATHENS, FEB 2020] |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | QUB-BI ANNUAL USA-SITE MEETING TO DISCUSS RESEARCH PROGRESS AND FUTURE PLANS |
Year(s) Of Engagement Activity | 2020 |
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 Speaker Presentation - Ascaris suum: local problem, global issue, experimental model (UCLA, Los Angeles, USA) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker presentation to research professionals at UCLA |
Year(s) Of Engagement Activity | 2018 |
Description | Invited talk, Hallem Lab, UCLA [NOVEMBER 2018] |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | 20 members of the Parasitology research group at UCLA attended a talk on the research associated with this award. |
Year(s) Of Engagement Activity | 2018 |
Description | Merial Animal Health PLC/Boehringer Ingelheim |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Members of QUB research team and BI Animal Health research and development collaboration team met to discuss progress and future plans (September 2017 UK; January 2018 GA, USA). Plans were made for research within the next 3 months and an arrangement was made for the next quarterly progress meeting. |
Year(s) Of Engagement Activity | 2017,2018 |
Description | Merial Animal Health Plc/Boehringer Ingelheim |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Members of QUB research team and Merial Animal Health Research and Development collaboration team met to discuss progress and future plans. Plans were made for research within the next three months and an arrangement was made for the next quarterly progress meeting. |
Year(s) Of Engagement Activity | 2016,2017 |
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 | Molecular Helminthology: An Integrated Approach, Cape Cod, MA, USA, 19-22 March 2017 (POSTER PRESENTATION, L. ATKINSON, An 'omics' approach to neuropeptide receptor deorphanisation in Ascaris suum) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | 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 |
Description | Molecular Helminthology: An Integrated Approach, San Antonio, TX, USA, 7-10 APRIL 2019 (ORAL PRESENTATION; F. McKAY; In silico profiling and prediction of putative neuropeptide ligand-receptor interactions in parasitic nematodes ) |
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 nematode neuropeptide system is a putative source of novel anthelmintic targets where available data support the prioritisation of neuropeptide G-protein coupled receptors (GPCRs). Exploitation of neuropeptide GPCRs as anthelmintic targets will require knowledge of neuropeptide and neuropeptide-GPCR complements across key nematode parasites, and an understanding of neuropeptide-receptor interactions. This study provides data on the Neuropeptide-Like Protein (NLP) profile of 9 key nematode parasite species representing different clades and lifestyles. These datasets are collated with existing nematode neuropeptide and neuropeptide-GPCR profiles to facilitate the prediction of putative ligand-receptor interactions that may occur in vivo. Ligand-receptor interaction predictions are aided by analyses of RNA-Seq expression data for key life-stages and tissue-types where spatial and temporal co-expression of a ligand and a receptor suggest greater potential for interaction. A BLAST approach using Caenorhabditis elegans NLP prepropeptides as search strings was employed to identify NLP sequelogues in nine parasite species. 323 NLP sequelogues were found (Table 1), with varying conservation of the C. elegans NLP profile. Analysis of neuropeptide and GPCR gene profiles across the nine species investigated in this study has revealed the complete conservation of seven ligands and seven neuropeptide receptors, underscoring their likely importance to nematode biology. Interestingly, these putative interactions include three ligand-receptor pairs which have previously been functionally and heterologously deorphanized in C. elegans. This provides validation of the in silico prediction platform and confidence that the additional putative ligand-receptor pairs can be functionally validated in parasites and/or C. elegans. In addition, a receptor de-orphanization 'pipeline' facilitates the identification of potentially interacting ligands and GPCRs across multiple different 'levels' such as within nematode clades, lifestyles, life stages and specific tissues (Figure 1). The in silico predictions presented here will inform nematode neuropeptide ligand-receptor de-oprhanization approaches and have the potential to expedite exploitation of neuropeptide GPCRs as anthelmintic targets. |
Year(s) Of Engagement Activity | 2019 |
Description | Molecular Helminthology: An Integrated Approach, San Antonio, TX, USA, 7-10 APRIL 2019 (ORAL PRESENTATION; A. MOUSLEY; Extra-synaptic volume transmission mediates neuropeptide signaling in Ascaris suum) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | ABSTRACT Our understanding of nematode nervous system function is founded on neural circuit synaptic interactions. However, other routes of non-synaptic communication are known in invertebrates including extra-synaptic (wireless) volume transmission (EVT), which enables close- or long-range communication where synaptic connections are absent. Although thought to be involved in Caenorhabditis elegans biogenic amine signaling, EVT has not yet been demonstrated in parasitic nematodes or for neuropeptide transmission. Curiously, in Ascaris suum, the FMRF-amide like peptides encoded by flp-18 potently stimulate reproductive tissues but are expressed anatomically distant from, and have no known synaptic connections to, these tissues. Here, for the first time, we report a non-synaptic mode of neuropeptide signaling in nematodes, mediated by the body cavity fluid (pseudocoelomic fluid; PCF). Using mass spectrometry and nematode physiology our data show that: (i) A. suum PCF contains a catalog of neuropeptide signaling molecules including neuropeptide-like proteins and FMRF-amide-like peptides; (ii) the FMRF-amide-like peptide, FLP-18 is dominates A. suum PCF; (iii) A. suum PCF potently modulates reproductive muscle function ex vivo; (iv) A. suum PCF also impacts C. elegans behaviour. These data support the role of extra-synaptic (wireless) routes of neuropeptide transmission in parasitic nematodes, and highlight the importance of non-neuronal signaling in the functional connectome. Importantly, these data also inform the complex receptor deorphanisation processes that underpin novel drug discovery programs for nematode pathogens. |
Year(s) Of Engagement Activity | 2019 |
Description | Molecular Helminthology: An Integrated Approach, San Antonio, TX, USA, 7-10 APRIL 2019 (POSTER PRESENTATION; L. ATKINSON; Novel in silico drug target prioritization pipelines in parasitic nematodes) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | ABSTRACT: Nematode parasites undermine animal health and global food security. Unfortunately the portfolio of chemicals currently used to control animal parasitic nematodes (APNs) is inadequate, resulting in a demand for new and improved approaches to the discovery of novel drugs to control APNs. Neuropeptide signalling system biology has been a central focus of nematode drug target discovery. Unfortunately, the identification and validation of neuropeptide (NP) G-protein coupled receptor (GPCRs) drug targets via heterologous expression has proven challenging. Parasite 'omics' resources provide an opportunity to exploit novel in silico anthelmintic drug target discovery pipelines as an alternative method of drug target identification and prioritization. In this study we have identified putative NP-GPCR orthologs of the 152 predicted C. elegans neuropeptide receptors in 10 key nematode parasites using Hidden Markov Models. These data show that parasitic nematodes have a reduced complement of C. elegans NP-GPCRs and several NP-GPCRs are conserved in parasitic nematodes. Using these data we have formulated a novel in silico NP-GPCR prioritization strategy which employs NP-GPCR conservation, C. elegans-derived phenotype, and parasite life-stage specific expression data which prioritizes parasitic nematode orthologs of eight Ce-NP-GPCRs |
Year(s) Of Engagement Activity | 2019 |
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 | Networking Workshop - Improving Clinical Helminth Infection Prevalence Data Using Molecular Diagnostics (Bangkok, Thailand) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Networking event delivery of research presentation (30 mins) |
Year(s) Of Engagement Activity | 2019 |
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: 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 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 research presentation Li lab at University of Wisconsin Madison (24th August 2022). |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Oral research presentation Li lab at University of Wisconsin Madison (24th August 2022). |
Year(s) Of Engagement Activity | 2022 |
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, 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 | 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 | Primary Life Sciences Scheme (March-June 2017; March-June 2018; March-June 2019; March-June 2020) |
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 (March-June 2017) 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 | 2017,2018,2019,2020 |
Description | Primary Life Sciences Scheme (March-June 2020) |
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 event to translate scientific research into the classroom, event based around nematode biology. |
Year(s) Of Engagement Activity | 2020 |
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 | 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 | 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 | 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 | The Neuropeptidergic System of Parasitic Nematodes: receptor deorphanisation approaches (INVITED SPEAKER: KU LEUVEN BELGIUM, 19-21 SEPTEMBER 2017) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The Neuropeptidergic System of Parasitic Nematodes: receptor deorphanisation approaches |
Year(s) Of Engagement Activity | 2017 |
Description | UK/THAILAND CONFERENCE - One Health Approach to Parasite Control in South East Asia (INVITED SPEAKER, BANGKOK, THAILAND, 19-21 JUNE 2017; Ascaris suum: local problem, global issue, experimental model) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Ascaris suum: local problem, global issue, experimental model |
Year(s) Of Engagement Activity | 2017 |
Description | UK/THAILAND RESEARCH GROUP MEETING - One Health Approach to Parasite Control in South East Asia |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | Research meeting designed to discuss, plan and disseminate research. |
Year(s) Of Engagement Activity | 2018 |
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 | 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 |