Dataset Information

Hit-and-Run Epigenetic Editing for Vectors of Snail-Borne Parasitic Diseases.

ABSTRACT: Snail-borne parasitic diseases represent an important challenge to human and animal health. Control strategies that target the intermediate snail host has proved very effective. Epigenetic mechanisms are involved in developmental processes and therefore play a fundamental role in developmental variation. DNA methylation is an important epigenetic information carrier in eukaryotes that plays a major role in the control of chromatin structure. Epigenome editing tools have been instrumental to demonstrate functional importance of this mark for gene expression in vertebrates. In invertebrates, such tools are missing, and the role of DNA methylation remains unknown. Here we demonstrate that methylome engineering can be used to modify in vivo the CpG methylation level of a target gene in the freshwater snail Biomphalaria glabrata, intermediate host of the human parasite Schistosoma mansoni. We used a dCas9-SunTag-DNMT3A complex and synthetic sgRNA to transfect B. glabrata embryos and observed an increase of CpG methylation at the target site in 50% of the hatching snails.

SUBMITTER: Luviano N

PROVIDER: S-EPMC8920497 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Hit-and-Run Epigenetic Editing for Vectors of Snail-Borne Parasitic Diseases.

Luviano Nelia N Duval David D Ittiprasert Wannaporn W Allienne Jean-Francois JF Tavernier Geneviève G Chaparro Cristian C Cosseau Celine C Grunau Christoph C

Frontiers in cell and developmental biology 20220228

Snail-borne parasitic diseases represent an important challenge to human and animal health. Control strategies that target the intermediate snail host has proved very effective. Epigenetic mechanisms are involved in developmental processes and therefore play a fundamental role in developmental variation. DNA methylation is an important epigenetic information carrier in eukaryotes that plays a major role in the control of chromatin structure. Epigenome editing tools have been instrumental to demo ...[more]

PMID: 35295851

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Project description:BackgroundFreshwater snails are the first obligatory intermediate hosts in the trematode life cycle. Several parasitic diseases transmitted by these snails are endemic in Africa, and their distribution closely follows that of the intermediate hosts. These diseases represent a major public health problem and cause significant socio-economic losses in Africa, particularly schistosomiasis and fascioliasis. In this review, we will describe the main roles of freshwater snails in the life cycle of trematode parasites, and the geographical distribution of these diseases in Africa. We will also discuss the different techniques for detecting parasitic infections in snails, as well as the various methods of controlling snails and the larval stages of parasites.MethodsWe carried out a literature search for articles dealing with parasitic diseases transmitted by freshwater snail hosts in Africa. The search was conducted in databases such as PubMed, Web of Science and Google Scholar using various search terms combined by Boolean operators. Our search was limited to peer-reviewed articles less than 10 years old. Articles published to date in the fields of control of parasitic diseases transmitted by freshwater snails were included. Results were presented in narrative and in table format.ResultsThe results of the database search identified 1007 records. We included 84 studies in this review. These studies generally focused on freshwater snails and the diseases they transmit. We described the geographical distribution of 43 freshwater species belonging to nine snail families, as well as the parasites that infect them. Several methods for diagnosing parasites in their snail hosts have been described, including microscopic and molecular methods, as well as antibody and protein barcode-based techniques. Molluscicides have been described as the main strategy for snail control.ConclusionThis study highlights several elements of knowledge about diseases transmitted by freshwater snails and their distribution. A good understanding of snail infection detection techniques and existing control methods is an essential component in adapting control strategies for these diseases.

Project description:BackgroundDynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking.ResultsHere, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run").ConclusionOur findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read-out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control.

Project description:IntroductionSchistosomiasis and fasciolosis are snail-borne diseases of great medical and veterinary health importance. The World Health Organization recommends complementing drug treatment with snail control and community involvement for disease elimination, but there is a general lack of snail experts and hence snail distribution data. Therefore, we adopted a citizen science approach and involved citizens in the monitoring of medically and veterinary important snail taxa.Materials and methodsSnail data was collected weekly by 25 trained citizen scientists (CSs) at 76 sites around southern Lake Albert (Uganda) for 20 months. At each site, snails were searched for 30 minutes, sorted, target snail hosts identified to genus level, counted and data submitted through a smartphone application. The quality of this data was assessed by comparing it to monthly data collected by an 'expert' malacologist using the same sampling protocol. Generalised binomial logistic and linear mixed-effects models were used to analyse the variables for agreement between the CSs and expert.FindingsThe binary agreement in presence/absence of Biomphalaria, Bulinus and Radix snails reported by the expert and CSs ranged between 70% and 86% (900 reports) with an average of 17% false negatives (sites wrongly defined as snail-free). The agreement for Biomphalaria and Radix increased with snail abundance, and false negatives decreased when the number of snails collected by citizens was aggregated per month. Site type significantly predicted binary agreement, which was lowest at lake sites (55%) and highest at spring sites (99%) with variations across genera. Similar temporal trends in snail abundance were recorded despite the expert reporting higher abundance. However, the relative abundance was consistent across site types. The match between the sites with highest Biomphalaria spp. abundance identified by CSs and expert was consistently high (~84.1%) and increased over time.Conclusions and recommendationsOur results demonstrate the potential of citizen science to map putative schistosomiasis transmission sites. We therefore argue that this inclusive, powerful and cost-effective approach can be more sustainable than top-down monitoring and intervention campaigns.

Dataset Information

Hit-and-Run Epigenetic Editing for Vectors of Snail-Borne Parasitic Diseases.

Publications

Hit-and-Run Epigenetic Editing for Vectors of Snail-Borne Parasitic Diseases.

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