Biology subjects

Ranford-Cartwright, L. C.

Publications and source records attributed to Ranford-Cartwright, L. C..

4 recordsLinked to original sources

bioRxiv2026

Febrile temperatures influence the transmission competence of mature Plasmodium falciparum gametocytes

Malaria transmission depends on the survival and mosquito infectivity of mature Plasmodium falciparum gametocytes. Despite malaria febrile episodes reaching 39 to 41.5{degrees}C in infected humans, the impact of febrile temperatures of varying durations on gametocyte viability and transmissibility remains undefined. Here we quantify the effects of exposing mature stage V gametocytes in vitro to febrile temperatures (39{degrees}C, 40{degrees}C, and 41.5{degrees}C) for varying durations (3 to 12 hours). To assess gametocyte morphology, functionality, and mosquito infectivity, we used light microscopy of Giemsa-stained thin blood smears, exflagellation assays, and standard membrane feeding assays (SMFAs). Following exposure to 39{degrees}C, gametocytes retained normal morphology, exflagellation capacity, and mosquito infectivity across all exposure durations. At 40{degrees}C, gametocytes remained morphologically intact and capable of exflagellation but exhibited a time-dependent reduction in mosquito infection, both in prevalence and oocyst intensity, following prolonged exposure. In contrast, exposure of mature gametocytes to 41.5{degrees}C, even for the minimum duration tested of 3 hours, resulted in complete loss of normal morphology, exflagellation capacity and ability to infect mosquitoes. These findings reveal that mosquito infectivity of mature gametocytes is affected both by the magnitude of the febrile temperature and the duration of exposure. This provides insight into how host fever dynamics may influence parasite transmission.

cell biology↗

bioRxiv2025

Regional adaptation to mosquito vectors shapes Plasmodium falciparum populations

Transmission of Plasmodium falciparum through mosquitoes represents the most severe population bottleneck in the parasites life cycle, yet the genetic basis of parasite-vector compatibility remains poorly understood. Here, we show that mosquito species-specific transmissibility depends on allelic variation in multiple P. falciparum genes expressed during midgut invasion, beyond the well-studied Pfs47. Using an allelic replacement strategy, we targeted highly geographically differentiated SNPs in P. falciparum that match regional variation in vector community composition. Transmissibility was compared across four mosquito species representing distinct geographic ranges (An. gambiae, An. stephensi, An. minimus, and An. albimanus). Two of five tested polymorphisms showed increased oocyst and sporozoite burdens in sympatric parasite-vector combinations compared to allopatric ones. Both substitutions occurred in ookinete micronemal proteins, CTRP and WARP, within von Willebrand factor A domains, suggesting that regional allelic variation modulates Plasmodium-vector compatibility by altering midgut adhesion interactions. These findings reveal that vector compatibility is a polygenic trait shaped by molecular interactions across several loci. Understanding this complexity refines models of parasite adaptation and can inform the design of transmission-blocking interventions effective across diverse vector-parasite combinations.

microbiology↗

bioRxiv2023

Estimating the number of breeders from helminth larvae with genomic data.

Effective control of helminth infections requires the application of mathematical models to inform control efforts and policy, the development of product profiles for new drugs, and the monitoring of existing drugs for resistance. Key to the success of these approaches is accurately estimating the number of worms within a host, as well as distinguishing, in drug efficacy trials and monitoring, between adults surviving treatment and adults who have reinfected a host following drug treatment. In practice, observing adult worms is often extremely challenging in a patient, as many adult helminths are embedded deep in host tissues. Genetic approaches to infer kinship between larvae or eggs offer a solution to establish adult worm burdens, and to distinguish between treatment failure or treatment success followed by reinfection. Here, we use low-coverage whole-genome, and mitochondrial sequencing, of Onchocerca volvulus larvae to estimate the number of adults contributing to pools of offspring of known and unknown parentage. lcWGS reconstructs full-sibling relationships, resolving the number of unique adult worms contributing to a pool of offspring. Mitochondrial genotyping reconstructs maternal sib-ship, thus estimating the minimum number of adult females within a patient. Further development will improve these techniques for evaluating adult worm burden and trial outcome.

genomics↗

bioRxiv2020

The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about mechanisms of transcriptional regulation. We profiled chromatin accessibility by ATAC-seq in laboratory-reared An. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that annotate to mosquito immune-response genes. This study is important not only for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information is of great potential for developing new mosquito-control and anti-malaria strategies.

genomics↗