Biology subjects

Golinelli, L.

Publications and source records attributed to Golinelli, L..

3 recordsLinked to original sources

bioRxiv2024

Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights into flp-gene evolution

BackgroundParasitic nematodes significantly undermine global human and animal health and productivity. Parasite control is reliant on anthelmintic administration however over-use of a limited number of drugs has resulted in escalating parasitic nematode resistance, threatening the sustainability of parasite control and underscoring an urgent need for the development of novel therapeutics. FMRFamide-like peptides (FLPs), the largest family of nematode neuropeptides, modulate nematode behaviours including those important for parasite survival, highlighting FLP receptors (FLP-GPCRs) as appealing putative novel anthelmintic targets. Advances in omics resources have enabled the identification of FLPs and neuropeptide-GPCRs in some parasitic nematodes, but remaining gaps in FLP-ligand libraries hinder the characterisation of receptor-ligand interactions, which are required to drive the development of novel control approaches. ResultsIn this study we exploited recent expansions in nematode genome data to identify 2143 flp-genes in >100 nematode species across free-living, entomopathogenic, plant, animal and human lifestyles and representing 7 of the 12 major nematode clades (1). Our data reveal that: (i) the phylum-spanning flps, flp-1, -8, -14, and -18, may be representative of the flp profile of the last common ancestor of nematodes; (ii) the majority of parasitic nematodes have a reduced flp complement relative to free-living species; (iii) FLP prepropeptide architecture is variable within and between flp-genes and across nematode species; (iv) FLP prepropeptide signatures facilitate flp-gene discrimination; (v) FLP motifs display variable length, amino acid sequence, and conservation; (vi) CLANS analysis provides insight into the evolutionary history of flp-gene sequelogues and reveals putative flp-gene paralogues and, (viii) flp expression is upregulated in the infective larval stage of several nematode parasites. ConclusionsThese data provide the foundation required for phylum-spanning FLP-GPCR deorphanisation screens in nematodes to seed the discovery and development of novel parasite control approaches.

evolutionary biology↗

bioRxiv2023

Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair

Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination of their action and their mutual interactions remains limited. Here, we demonstrate that two neuropeptides, NLP-10 and FLP-1, released from the same interneuron pair, AVKL/R, exert antagonistic effects on locomotion speed in Caenorhabditis elegans. NLP-10 accelerates locomotion by activating the G protein-coupled receptor NPR- 35 on premotor interneurons that promote forward movement. Notably, we establish that NLP-10 is crucial for the aversive response to mechanical and noxious light stimuli. Conversely, AVK-derived FLP-1 slows down locomotion by suppressing the secretion of NLP-10 from AVK, through autocrine feedback via activation of its receptor DMSR-7 in AVK neurons. Our findings suggest that peptidergic autocrine motifs, exemplified by the interaction between NLP-10 and FLP-1, might represent a widespread mechanism in nervous systems across species. These mutual functional interactions among peptidergic co-transmitters could fine-tune brain activity. Highlights* A pair of neurons elicits opposing behaviors via two distinct neuropeptides * The neuropeptide NLP-10 accelerates locomotion by activating premotor interneurons * Release of the neuropeptide FLP-1 reduces NLP-10 release via autocrine feedback * NLP-10 is crucial for escaping aversive mechanical stimuli and noxious blue light eTOC blurbNeuropeptidergic communication is complex due to the hundreds of proteinaceous transmitters and receptors involved. Aoki and colleagues demonstrate a further layer of regulation, where one neuropeptide negatively influences release of an antagonistic neuropeptide by autocrine feedback, in a single neuron pair. This may represent a general principle in neuropeptidergic signaling.

neuroscience↗

bioRxiv2023

Automated scoring of nematode nictation on a textured background

Entomopathogenic nematodes, including Steinernema spp., play an increasingly important role as biological alternatives to chemical pesticides. The infective juveniles of these worms use nictation - a behavior in which animals stand on their tails - as a host-seeking strategy. The developmentally-equivalent dauer larvae of the free-living nematode Caenorhabditis elegans also nictate, but as a means of phoresy or "hitching a ride" to a new food source. Advanced genetic and experimental tools have been developed for C. elegans, but time-consuming manual scoring of nictation slows efforts to understand this behavior, and the textured substrates required for nictation can frustrate traditional machine vision segmentation algorithms. Here we present a Mask R-CNN-based tracker capable of segmenting C. elegans dauers and S. carpocapsae infective juveniles on a textured background suitable for nictation, and a machine learning pipeline that scores nictation behavior. We use our system to show that the nictation propensity of C. elegans from high-density liquid cultures largely mirrors their development into dauers, and to quantify nictation in S. carpocapsae infective juveniles in the presence of a potential host. This system is an improvement upon existing intensity-based tracking algorithms and human scoring which can facilitate large-scale studies of nictation and potentially other nematode behaviors.

animal behavior and cognition↗