Chemist targets pesky mosquitoes’ genes

Researchers at the University of Cincinnati examined genetic material of three species of mosquito responsible for killing millions of people around the world each year. In a collaboration between UC's chemistry and biology departments, researchers revealed the surprising genetic modifications female mosquitoes undergo, in part to create the next generation.

Using tools called liquid chromatography-tandem mass spectrometry, researchers found as many as 33 genetic modifications in the transfer RNA of female mosquitoes. Like DNA, transfer RNA serves as the building blocks of life, communicating the genetic code from DNA to build new proteins that regulate the body's tissues and organs.

"That's important because it means there are different requirements for making proteins in males and females," said Melissa Kelley, lead author and a postdoctoral researcher in UC's College of Arts and Sciences.

"Proteins do a bunch of things: they do the housekeeping needed to keep an organism alive. And there are specialized ones that are created like when females are getting ready to lay eggs," Kelley said.

By better understanding these modifications at the molecular level, scientists might be able to find a new weapon to control mosquito populations.

UC is not alone. Researchers around the world are looking at ways to target the genes of mosquitoes to prevent mosquito-borne disease.

Mosquitoes cause more human misery than virtually any other pest. More than 229 million people were diagnosed with malaria in 2019. Mosquitoes also carry yellow fever, Dengue fever and West Nile virus, among others.

"There is a constant need for new methods of control," Kelley said.

Mosquitoes were responsible for reshaping entire landscapes in the United States. Mosquito-control commissions funded with federal dollars launched massive projects to drain and fill wetlands in the 1930s. Pesticides soon replaced labor-intensive water management policies. The popular insect-killer DDT was banned in 1972 after research discovered the toxin was accumulating in the food chain and affecting wildlife such as bald eagles.

Various tools are used to fight mosquitoes, from dispersing fish that feast on mosquito larvae to releasing hordes of sterile males into the wild. But pesticides remain a popular solution.

"And there have been reports of increased pesticide resistance in mosquitoes," Kelley said.

UC chemist Patrick Limbach, UC's vice president for research, was a co-author of the paper.

"As carriers of multiple human diseases, understanding the mechanisms behind mosquito reproduction may have implications for remediation strategies," Limbach said.

Students cultivate six species of mosquito in biologist and associate professor Joshua Benoit's lab.

UC studied three of them for the genetic study: Aedes aegypti, Culex pipiens and Anopheles stephensi. The first, found in Africa, the Mediterranean and the southeastern United States, is a known vector for yellow fever, dengue, Zika virus and chikungunya. Culex pipiens is a mosquito found around the world and has been linked to West Nile virus. The last is an Asian mosquito that has been linked to malaria outbreaks. All three species require a blood meal for reproduction.

Female and male mosquitoes have obvious physical differences. Typically smaller with fuzzy antennae, male mosquitoes don't suck blood like females that need nutrients to make the next generation.

"We were curious if there were differences in how they make proteins," Kelley said.

UC researchers found that female mosquitoes have a higher abundance of tRNA modifications than males. Female mosquitoes likely utilize chemical modifications to tRNA more abundantly than males, which could underlie factors associated with female reproduction.

UC undergraduate biology student Melissa Uhran said she was fortunate to take part in the study.

"It was a great opportunity. I'm grateful to get a chance to do it. It's given me a lot of experience that will help me career-wise," she said. "And I've learned a lot."

UC's project was supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.