# A genome-wide CRISPR screen in Anopheles mosquito cells identifies fitness and immune cell function-related genes

## TL;DR

This study uses CRISPR screens in Anopheles mosquitoes to identify genes important for their survival and immune cell function, which could help in controlling malaria transmission.

## Contribution

The study introduces a genome-wide CRISPR platform in Anopheles mosquitoes and identifies genes critical for fitness and immune cell function.

## Key findings

- A genome-wide CRISPR screen identified 1280 fitness-related genes in Anopheles mosquito cells.
- Genes conferring resistance to clodronate liposomes were identified and validated in vivo.
- New mechanistic insights into phagolysosome formation and clodronate liposome processing were revealed.

## Abstract

Anopheles mosquitoes are the sole vector of malaria, the most burdensome vector-borne disease worldwide. At present, strategies for reducing mosquito populations or limiting their ability to transmit disease show the most promise for disease control. Therefore, improving our understanding of mosquito biology and immune function may aid new approaches to limit malaria transmission. Here, we perform genome-wide CRISPR screens in Anopheles mosquito cells to identify genes required for fitness and that confer resistance to clodronate liposomes, which are used to ablate immune cells. The cellular fitness screen identifies 1280 fitness-related genes (393 at highest confidence) that are highly enriched for roles in fundamental cell processes. The clodronate screen identifies resistance factors that impair clodronate liposome function. For the latter, we confirm roles in liposome uptake and processing through in vivo validation in Anopheles gambiae that provide new mechanistic detail of phagolysosome formation and clodronate liposome processing. Altogether, we present a genome-wide CRISPR knockout platform in a major malaria vector and identify genes important for fitness and immune-related processes.

Mosquitoes are major vectors for the transmission of many serious pathogens. This study uses genome-wide CRISPR screens in the mosquito, Anopheles gambiae, to reveal new insights into mosquito fitness and the function of clodronate-liposome mediated immune cell ablation.