Virginia Tech Mosquito Research Provides Hope for Malaria Control

malaria
Ph.D. student Jiang-Tao Liang (left) and Professor Igor Sharakhov (right) from the Department of Entomology in the College of Agriculture and Life Sciences

According to the World malaria report 2018 from the World Health Organization, there were 219 million cases of malaria worldwide with 435,000 deaths in 2017. The majority of these deaths were children living in Africa.

“In the last 15 years, malaria was on a steady decline. However, after 2015, insecticide resistance brought an end to that decline. We can control malaria in several ways, such as by creating new insecticides or developing and introducing genetic methods of mosquito control,” said Igor Sharakhov, a professor in the Department of  Entomology in the College of Agriculture and Life Sciences at Virginia Tech.

Sharakhov is studying how malaria can be controlled by reducing the reproduction of mosquitoes.

Four mosquito species within the Anopheles gambiae complex can spread malaria to humans by injecting Plasmodium parasites into the bloodstream when feeding on human blood. Ultimately, these parasites enter the human’s red blood cells, leading to fever and flu-like symptoms, which, in rare cases, can lead to serious organ failures and abnormalities in the blood.

Since this parasite is a complex unicellular organism, it is difficult to develop effective drugs and vaccines against it. As drug and pesticide resistance is on the rise, scientists must look to other methods for mosquito control.

Sharakhov has suggested an approach that involves genetically modifying the males so that they are “fit” enough to sexually reproduce with females in the wild but are sterile. It is essential that sterile males can compete with wild males in order to reproduce with wild females. If successful, the females will produce eggs that will not hatch.

Their findings were recently published in Proceedings of the Royal Society B.  

To create sterile male mosquitoes, researchers cross similar, but different, species from within the Anopheles gambiae complex in a process known as hybridization. In this study, Anopheles gambiaeAnopheles coluzzii, and Anopheles merus mosquitoes were tested. By crossing a male from one species with a female from another species, researchers can see which traits get enhanced or diminished.

“Mosquitoes have just three pairs of chromosomes. The X and Y sex chromosomes can vary across different species. Like humans, females have two X chromosomes, and males have both an X and a Y chromosome. When hybridization happens between organisms with different sex chromosomes, it can cause cellular and developmental failures that can ultimately lead to sterility,” said Sharakhov, who is also an affiliated faculty member of the Fralin Life Sciences Institute at Virginia Tech.

Sharakhov and Jiang-Tao Liang, a Ph.D. student in the Department of Entomology, wanted to know more about sterility and the cellular and genetic mechanisms that come into play. They started by crossing different species and observed the abnormalities using high-resolution microscopy. What they found was developmental arrest.

By crossing a female An. gambiae or An. coluzzi mosquito with a male An. merus mosquito, Sharakhov’s team found that the testes, which are the reproductive organs of males, stopped developing on a cellular level. As a result, they were significantly smaller and lacked the cells that are necessary to generate sperm.

When the team crossed a female An. merus and a male An. gambiae or An. coluzzi, they noticed that the sperm had experienced chromosomal failures. In turn, each sperm had a large head and two tails, which makes sperm movement and egg fertilization virtually impossible. These changes were visualized using fluorescent in situ hybridization (FISH) imaging.

Fluorescent in situ hybridization (FISH) imaging
Fluorescent in situ hybridization imaging illustrating chromosomal abnormalities that lead to male hybrid sterility in Anopheles mosquitoes. Image courtesy of the Sharakhov lab.

One of the most difficult elements of mosquito control is ensuring that the sterility stays within these few species while also having the least impact on the ecosystem. Identifying the genes that are responsible for male sterility can help researchers like Sharakhov and Liang ensure that sterility stays within a select number of species.

“Ideally, we would like to target those mosquitoes that are associated with causing harm to humans. Our research can help with that because we can identify those genes that create barriers between species,” said Liang.

Most other studies on speciation, which were done in Drosophila, or fruit flies, concluded that hybrid male sterility has little or nothing to do with cell division or chromosome pairing. However, Sharakhov and Liang found that this is not the case, at least in mosquitoes.

“I came across one study in Drosophila by Theodosius Dobzhansky, one of the founders of evolutionary biology, that found very similar problems to what we found. However, he published in an obscure German journal and his paper is rarely cited. We cited it in ours and it looks like it could be a more common mechanism of sterility, especially in mosquitoes,” said Sharakhov.

In the future, Sharakhov and Liang hope to further investigate gene expression in hybrids and normal species to see what genes are mis-expressed and how they can induce, and even rescue, fertility using genetic manipulation.