Nematode neuropeptides as transgenic nematicides

NDW was supported by a Bill and Melinda Gates Foundation grand challenge exploration grant. LW was supported by a PhD studentship from the EUPHRESCO Plant Health Fellowship Scheme, and an Eaton Visitorship Award. JJD was supported by a Leverhulme Trust early career fellowship and a Bill and Melinda Gates Foundation grand challenge exploration grant.Plant parasitic nematodes (PPNs) seriously threaten global food security. Conventionally an integrated approach to PPN management has relied heavily on carbamate, organophosphate and fumigant nematicides which are now being withdrawn over environmental health and safety concerns. This progressive withdrawal has left a significant shortcoming in our ability to manage these economically important parasites, and highlights the need for novel and robust control methods. Nematodes can assimilate exogenous peptides through retrograde transport along the chemosensory amphid neurons. Peptides can accumulate within cells of the central nerve ring and can elicit physiological effects when released to interact with receptors on adjoining cells. We have profiled bioactive neuropeptides from the neuropeptide-like protein (NLP) family of PPNs as novel nematicides, and have identified numerous discrete NLPs that negatively impact chemosensation, host invasion and stylet thrusting of the root knot nematode Meloidogyne incognita and the potato cyst nematode Globodera pallida. Transgenic secretion of these peptides from the rhizobacterium, Bacillus subtilis, and the terrestrial microalgae Chlamydomonas reinhardtii reduce tomato infection levels by up to 90% when compared with controls. These data pave the way for the exploitation of nematode neuropeptides as a novel class of plant protective nematicide, using novel non-food transgenic delivery systems which could be deployed on farmer-preferred cultivars

Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease

Publication history: Accepted - 11 September 2021; Published online - 19 September 2021.Background: Whole transgenic or non-transgenic organism model systems allow the screening of pharmacological compounds for protective actions in Alzheimer’s disease (AD). Aim: In this study, a plant parasitic nematode, Globodera pallida, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. Methods: Fresh second-stage juveniles of G. pallida were used to measure their chemosensory, perform immunocytochemistry on their neurological structures, evaluate their survival rate, measure reactive oxygen species, and determine total oxidized glutathione to reduced glutathione ratio (GSSG/GSH) levels, before and after treatment with 100 µM of various amyloid beta (Aβ) peptides (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16). Wild-type N2 C. elegans (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) G. pallida (unlike Caenorhabditis elegans) assimilates amyloid-β (Aβ) peptides which co-localise with its neurological structures; (ii) pre-treatment with various Aβ isoforms (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16) impairs G. pallida’s chemotaxis to differing extents; (iii) Aβ peptides reduced survival, increased the production of ROS, and increased GSSG/GSH levels in this model; (iv) this unique model can distinguish differences between different treatment concentrations, durations, and modalities, displaying good sensitivity; (v) clinically approved neuroprotective agents were effective in protecting G. pallida from Aβ (1–42) exposure. Taken together, the data indicate that G. pallida is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.N.A.A. received a PhD studentship from Shaqra University, KSA and the Saudi Cultural Bureau in London (UKSACB). B.D.G.’s laboratory has received support for AD research from Alzheimer’s Research UK (ARUK-NC2019-NI), the Medical Research Council (MRC) (CIC-CD1718- CIC25), US-Ireland Health and Social Care NI (HSC R&DST/5460/2018) and InvestNI (RD101427 11-01-17-008). This work was also supported by Shaqra University, Saudi Arabi

RNAi Effector Diversity in Nematodes

While RNA interference (RNAi) has been deployed to facilitate gene function studies in diverse helminths, parasitic nematodes appear variably susceptible. To test if this is due to inter-species differences in RNAi effector complements, we performed a primary sequence similarity survey for orthologs of 77 Caenorhabditis elegans RNAi pathway proteins in 13 nematode species for which genomic or transcriptomic datasets were available, with all outputs subjected to domain-structure verification. Our dataset spanned transcriptomes of Ancylostoma caninum and Oesophagostomum dentatum, and genomes of Trichinella spiralis, Ascaris suum, Brugia malayi, Haemonchus contortus, Meloidogyne hapla, Meloidogyne incognita and Pristionchus pacificus, as well as the Caenorhabditis species C. brenneri, C. briggsae, C. japonica and C. remanei, and revealed that: (i) Most of the C. elegans proteins responsible for uptake and spread of exogenously applied double stranded (ds)RNA are absent from parasitic species, including RNAi-competent plant-nematodes; (ii) The Argonautes (AGOs) responsible for gene expression regulation in C. elegans are broadly conserved, unlike those recruited during the induction of RNAi by exogenous dsRNA; (iii) Secondary Argonautes (SAGOs) are poorly conserved, and the nuclear AGO NRDE-3 was not identified in any parasite; (iv) All five Caenorhabditis spp. possess an expanded RNAi effector repertoire relative to the parasitic nematodes, consistent with the propensity for gene loss in nematode parasites; (v) In spite of the quantitative differences in RNAi effector complements across nematode species, all displayed qualitatively similar coverage of functional protein groups. In summary, we could not identify RNAi effector deficiencies that associate with reduced susceptibility in parasitic nematodes. Indeed, similarities in the RNAi effector complements of RNAi refractory and competent nematode parasites support the broad applicability of this research genetic tool in nematodes

Local stability properties of complex, species-rich soil food webs with functional block structure

Publication history: Accepted - 14 October 2021; Published online - 3 November 2021.Ecologists have long debated the properties that confer stability to complex, species-rich ecological networks. Species-level soil food webs are large and structured networks of central importance to ecosystem functioning. Here, we conducted an analysis of the stability properties of an up-to-date set of theoretical soil food web models that account both for realistic levels of species richness and the most recent views on the topological structure (who is connected to whom) of these food webs. The stability of the network was best explained by two factors: strong correlations between interaction strengths and the blocked, nonrandom trophic structure of the web. These two factors could stabilize our model food webs even at the high levels of species richness that are typically found in soil, and that would make random systems very unstable. Also, the stability of our soil food webs is well-approximated by the cascade model. This result suggests that stability could emerge from the hierarchical structure of the functional organization of the web. Our study shows that under the assumption of equilibrium and small perturbations, theoretical soil food webs possess a topological structure that allows them to be complex yet more locally stable than their random counterpart. In particular, results strongly support the general hypothesis that the stability of rich and complex soil food webs is mostly driven by correlations in interaction strength and the organization of the soil food web into functional groups. The implication is that in real-world food web, any force disrupting the functional structure and distribution pattern of interaction strengths (i.e., energy fluxes) of the soil food webs will destabilize the dynamics of the system, leading to species extinction and major changes in the relative abundances of species.TC was supported by the project SENSE (Structure and Ecological Niche in the Soil Environment; EC FP7 –631399 –SENSE). TC and FdC were also supported by the NERC Grant Controls on the stability of soils and their functioning under land use and climate change (NE/M017036/1) as was RDB (NE/M017028/1). MÖ was supported by the European Regional Development Fund [Centre of Excellence EcolChange]