Tag Archives: biochemistry

Exploring genetics to combat malaria and Zika

Fralin Life Science Institute’s Vector-Borne Disease Research Group team members, from left: Zhijian “Jake” Tu, professor of biochemistry; Brantley Hall, biochemistry graduate student; Atashi Sharma, entomology graduate student; and Igor Sharakhov, associate professor of entomology

Fralin Life Science Institute’s Vector-Borne Disease Research Group team members, from left: Zhijian “Jake” Tu, professor of biochemistry; Brantley Hall, biochemistry graduate student; Atashi Sharma, entomology graduate student; and Igor Sharakhov, associate professor of entomology

The Zika virus has quickly become a major health threat, and researchers at Virginia Tech are looking for ways to curtail its spread.

The virus, which is primarily spread to humans by the bite of an infected mosquito, has been passed on to a growing number of Americans since early 2016, and the World Health Organization has declared it a Public Health Emergency of International Concern.

Biochemist Zhijian “Jake”  Tu is one of several Virginia Tech researchers zeroing in on the Zika virus. Tu is studying genes that turn biting female mosquitoes into males, and he is exploring genetic strategies to stop the transmission of the Zika virus by reducing the number of female mosquitoes. Male mosquitoes do not bite and are harmless to humans, while female mosquitoes bite humans to get the blood they need for egg production.

With support from an NIH grant and building on their previous discoveries that were published in the journal Science, Tu and some of his colleagues in the Vector-Borne Disease Research Group — Zach Adelman, Jinsong Zhu, and Maria Sharakhova — are investigating the molecular mechanisms and applications of male-determining factor in Aedes agypti mosquitoes, the species that transmits Zika.

Tu, Zhu, and Igor Sharakhov also received NIH funding to study sex determination in a family of malaria-spreading mosquitoes. Working with a large international consortium, the researchers sequenced the “Y” chromosome — the genetic drive of sex determination and male fertility — in Anopheles gambiae mosquitoes. The findings were published in the Proceedings of the National Academy of Sciences.

“Although the master switch genes that govern sex determination are completely different in Aedes and Anopheles mosquitoes, the approach that targets the female mosquitoes will have broad applications in efforts to control numerous mosquito-borne infectious diseases, including old foes such as malaria and emerging threats such as Zika,”  Tu said.

While Zika had only previously been associated with mild symptoms in humans, it can produce more severe symptoms in areas where the virus has recently been introduced because populations have no pre-existing immunity. It has also been linked to a birth defect called “microcephaly,” in which infected pregnant women give birth to brain-damaged babies with abnormally small heads.

About 10 Virginia Tech researchers with expertise in the fields of disease modeling, epidemic mapping, mosquito genetics, and novel insecticides are now focusing on Zika, developing ways to predict the spread of the virus and stop it from doing more damage.

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Virginia Tech researcher discovers possible drug target for sleeping sickness

Zachary Mackey

Zachary Mackey in Biochemistry is doing research on how to cure sleeping sickness, which is carried by the tsetse fly.

Zachary Mackey is trying to deliver a stern wake-up call to the parasite that causes sleeping sickness, a neurological disease that threatens millions of lives in 36 countries in Africa, according to the World Health Organization.

Mackey identified a protein vital to the sleeping sickness parasite’s good health. Disrupting the protein with drugs could potentially make it impossible for the parasite to reproduce and survive, and thereby reducing its danger to human health.

The discovery suggests multiple ways to disrupt the protein’s function, said Mackey, an assistant professor of biochemistry in the College of Agriculture and Life Sciences, an affiliated faculty member in the Fralin Life Science Institute, and an affiliated researcher in Virginia Tech’s Vector-Borne Disease Research Group.

Sleeping sickness is caused when the vector-borne parasite Trypanosoma brucei crosses the blood-brain barrier during the late stage of infection.

The native African tsetse fly transmits the parasite through a painful bite, allowing it to spread through the body, causing fever, headache, and intense aches and pains.

When the parasite spreads to the brain, it causes swelling, slurred speech, confusion, and difficulty walking, followed by coma and eventually death.

Mackey thinks that overexpressing, depleting, or blocking the protein — known as proliferating cell nuclear antigen — represents three ways this protein could be targeted in the parasite, broadening the types of small molecules or drugs that can be developed to treat the disease.

Though a few drugs currently exist, they are either very expensive or have extremely powerful side effects due to their toxicity, according to Mackey, who is also an affiliated researcher in the Virginia Tech Center for Drug Discovery.

Mackey now investigates how altering the amount of protein kills the parasite. Once he better understands how this protein regulates the parasite’s life cycle, he can partner with chemists to synthesize small molecules that target the protein’s disruption.

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