The National Institutes of Health's Institute of Allergy and Infectious Disease awarded more than $2.8 million in grants to Jason Rasgon, professor at Penn State, for mosquito genetics research aimed at curbing the spread of deadly diseases, according to a July 29 announcement.
Rasgon said the projects could lower technical barriers for researchers studying mosquito genetics and eventually enable new discoveries that might help inhibit the transmission of dangerous pathogens such as zika, yellow fever, dengue, and malaria. "We hope to build tools to make genetic manipulation of mosquitoes—and potentially other arthropods—easy across laboratories," Rasgon said. "Although the two projects take different approaches, both are rooted in the same idea: using modern genetic and synthetic biology tools to introduce desired traits into individual mosquitoes and, potentially, mosquito populations."
The first grant will focus on developing a model system to better understand how bacteria establish symbiosis with mosquitoes. This builds on previous work in Rasgon's lab supported by a Huck Innovative & Transformational Seed Fund grant. The project takes inspiration from Wolbachia bacteria, which is used in some areas to control vector-borne diseases because female mosquitoes infected with Wolbachia have reduced ability to transmit pathogens. However, Rasgon said success varies due to breakdowns in symbiotic relationships: "We have a poor understanding of the biological phenomena underpinning the evolution and maintenance of symbiosis because Wolbachia cannot be manipulated or engineered." The team aims to develop an artificial symbiotic relationship that is easier for researchers to manipulate than naturally occurring endosymbionts.
Using synthetic biology techniques, researchers plan first to modify E. coli so it displays a peptide tag recognized by developing mosquito eggs. They then intend to engineer mosquitoes dependent on vitamin B6 supplied by these bacteria. If successful, this would create a stable inherited relationship between insects and engineered microbes—a new model system for studying symbiosis that could inform future disease control strategies.
The second funded project will use an insect-specific virus harmless to humans as a delivery vehicle for gene-editing payloads inside mosquitoes using CRISPR technology—a method previously demonstrated by Rasgon's lab called ReMOT Control but now expanded beyond gene deletion toward inserting new genetic material. Researchers will test if this virus can induce heritable genetic changes in mosquito offspring or mimic reproductive outcomes similar to those produced by Wolbachia but with greater precision.
If successful, these efforts may provide scientists with tunable platforms both for investigating molecular interactions involved in pathogen transmission and ultimately manipulating them.
