Biology subjects

Rinvee, T. A.

Publications and source records attributed to Rinvee, T. A..

3 recordsLinked to original sources

bioRxiv2025

JNK signaling regulates reproductive trade-offs after Plasmodium infection in the malaria mosquito

Environmental stress can limit mammalian reproduction by affecting production of sexual steroid hormones. Here we reveal a similar mechanism in the malarial mosquito Anopheles gambiae: activation of the stress-sensitive c-Jun N-terminal kinase, JNK, constrains reproductive investment by suppressing production of ecdysteroids that orchestrate egg development in this species. We show that infection with Plasmodium berghei parasites increases JNK signalling in the reproductive tract causing a JNK-dependent reduction in both egg development and mosquito survival. Moreover, JNK signaling supresses expression of Cyp315a1 (AGAP000284), a rate-limiting enzyme in ecdysteroid synthesis, a transcriptional change reflected in reduced ecdysteroid production following an infected blood meal. A similar mechanism limits egg production under other stressors (heat stress, or ectopic activation of JNK signaling). Together, these data reveal a regulatory circuit whereby Plasmodium infection curtails reproductive investment in an important vector of human malaria, one that may be applicable to environmental stressors more generally.

zoology↗

bioRxiv2025

OocystMeter, a machine-learning algorithm to count and measure Plasmodium oocysts, reveals clustering patterns in the Anopheles midgut

We present OocystMeter, a machine learning-based software developed to automate the segmentation of malaria oocysts from images of mosquito midguts stained with mercurochrome. Existing bioimage analysis tools, including machine learning-based ones, often struggle with the unique staining patterns, complex midgut backgrounds, and variable morphology of oocysts, making the determination of oocyst size and numbers cumbersome. To overcome these challenges, we curated a high-quality dataset comprised of 11,178 Plasmodium falciparum oocysts in Anopheles gambiae midguts annotated by expert parasitologists. Using this dataset, we fine-tuned a Mask R-CNN object detection model to achieve segmentation accuracy comparable to human parasitologists (Spearmans correlation of 0.998 for oocyst counts and 0.978 for size measurements). Applying this tool in conjunction with spatial analysis, we uncovered a non-random, clustered spatial distribution of oocysts independent of the midguts anatomical regions or geometric axes, particularly in infections with fewer than 75 oocysts/midgut. Our workflow significantly accelerates malaria oocyst intensity and size analysis, reduces human bias, and provides spatial coordinates for advanced parasitology studies. OocystMeter is freely available at https://github.com/duopeng/OocystMeter, and as a web tool at http://Oocystmeter.org/, offering a valuable resource for researchers investigating the oocyst stage of malaria development.

bioinformatics↗

bioRxiv2024

Mapping Plasmodium transitions and interactions in the Anopheles female

The human malaria parasite, Plasmodium falciparum, relies exclusively on Anopheles mosquitoes for transmission. Once ingested during blood feeding, most parasites die in the mosquito midgut lumen or during epithelium traversal1. How surviving ookinetes interact with midgut cells and form oocysts is poorly known, yet these steps are essential to initiate a remarkable growth process culminating in the production of thousands of infectious sporozoites2. Here, using single-cell RNA sequencing of both parasites and mosquito cells across different developmental stages and metabolic conditions, we unveil key transitions and mosquito-parasite interactions occurring in the midgut. Functional analyses uncover processes regulating oocyst growth and identify the transcription factor PfSIP2 as essential for sporozoite infection of human hepatocytes. Combining shared mosquito-parasite barcode analysis with confocal microscopy, we reveal that parasites preferentially interact with midgut progenitor cells during epithelial crossing, potentially using their basal location as an exit landmark. Additionally, we show tight connections between extracellular late oocysts and surrounding muscle cells that may ensure parasites adherence to the midgut. We confirm our major findings in several mosquito-parasite combinations, including field-derived parasites. Our study provides fundamental insight into the molecular events characterizing previously inaccessible biological transitions and mosquito-parasite interactions, and identifies candidates for transmission-blocking strategies.

microbiology↗