Creative Minds: Building a CRISPR Gene Drive Against Malaria

Valentino Gantz

Valentino Gantz/Credit: Erik Jepsen

Researchers have used Drosophila melanogaster, the common fruit fly that sometimes hovers around kitchens, to make seminal discoveries involving genetics, the nervous system, and behavior, just to name a few. Could a new life-saving approach to prevent malaria be next? Valentino Gantz, a researcher at the University of California, San Diego, is on a path to answer that question.

Gantz has received a 2016 NIH Director’s Early Independence Award to use Drosophila to hone a new bioengineered tool that acts as a so-called “gene drive,” which spreads a new genetically encoded trait through a population much faster than would otherwise be possible. The lessons learned while working with flies will ultimately be applied to developing a more foolproof system for use in mosquitoes with the hope of stopping the transmission of malaria and potentially other serious mosquito-borne diseases.

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Gene Drive Research Takes Aim at Malaria

Mosquitoes and a Double HelixMalaria has afflicted humans for millennia. Even today, the mosquito-borne, parasitic disease claims more than a half-million lives annually [1]. Now, in a study that has raised both hope and concern, researchers have taken aim at this ancient scourge by using one of modern science’s most powerful new technologies—the CRISPR/Cas9 gene-editing tool—to turn mosquitoes from dangerous malaria vectors into allies against infection [2].

The secret behind this new strategy is the “gene drive,” which involves engineering an organism’s genome in a way that intentionally spreads, or drives, a trait through its population much faster than is possible by normal Mendelian inheritance. The concept of gene drive has been around since the late 1960s [3]; but until the recent arrival of highly precise gene editing tools like CRISPR/Cas9, the approach was largely theoretical. In the new work, researchers inserted into a precise location in the mosquito chromosome, a recombinant DNA segment designed to block transmission of malaria parasites. Importantly, this segment also contained a gene drive designed to ensure the trait was inherited with extreme efficiency. And efficient it was! When the gene-drive engineered mosquitoes were mated with normal mosquitoes in the lab, they passed on the malaria-blocking trait to 99.5 percent of their offspring (as opposed to 50 percent for Mendelian inheritance).

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Climate and Viral Illness: El Niño Event Linked to Dengue Epidemics

Dengue Incidence Score Video
Caption: Incidence of dengue fever across Southeast Asia, 1993-2010. Note increasing incidence (red) starting about June 1997, which corresponds to a period of higher temperatures driven by a strong El Niño. At the end of the El Niño event, in January 1999, dengue incidence is much lower (green). Credit: Wilbert Van Panhuis, University of Pittsburgh

Just as the severity of the winter flu fluctuates from year to year in the United States, dengue fever can rage through tropical and subtropical regions of the world during their annual rainy seasons, causing potentially life-threatening high fever, severe joint pain, and bleeding. Other years—for still unknown reasons—dengue fizzles out. While many nations monitor the incidence of dengue within their borders, their data aren’t always combined to track outbreaks across wider regions over longer times.

Now, NIH-funded researchers and colleagues, reporting in Proceedings of the National Academy of Sciences [1], have linked an intense dengue epidemic that struck eight Southeast Asian countries starting in mid-1997 to high temperatures driven by the strongest El Niño event in recent times. El Niño is a complex, irregularly occurring series of climate changes in the Pacific Ocean with a global impact on weather patterns. This new insight into climatic factors associated with dengue transmission could enable better prevention measures, which may soon be needed because climatologists are predicting another strong El Niño event next year due to unusually high ocean temperatures in the equatorial Pacific. Continue reading

LabTV: Curious About Malaria

Elyse MunozIt’s the time of year when thoughts turn to buying school supplies and heading back to the classroom or off to university. So, throughout the month of August, I’ll be sharing LabTV profiles of young people whose learning experiences have set them on the path to becoming biomedical researchers.

One of the great things about college is that you never know where those four years might lead you. Elyse Munoz, who’s the focus of today’s video, offers an excellent case in point. Upon enrolling at Arizona State University, Tempe, she chose political science as her major—only to find the classes “incredibly boring.” Then a friend talked Munoz into taking an anatomy class, and suddenly everything clicked: she discovered biology was her true calling.

Now, Munoz is a candidate for a Ph.D. in genetics at Pennsylvania State University, State College. Working in the lab of molecular parasitologist Scott Lindner, Munoz is contributing to the search for promising vaccine targets for malaria, a mosquito-borne disease that kills more than a half-million people, mainly children under the age of 5, around the globe each year.

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Fighting Malaria, With a Little Help from Bacteria

photo of a red-bellied mosquito adjacet to a photo of pink blobs

Caption: Anopheles female blood feeding and Plasmodium falciparum eggs in Anopheles mosquito midguts.
Credit: Image courtesy of Jose Luis Ramirez, Laboratory of Malaria and Vector Research, NIAID, NIH

It turns out that one of the most innovative and effective strategies to fight malaria might involve harnessing a bacterium called Wolbachia. This naturally occurring genus of bacteria infects many species of insects, including mosquitoes. The reason this is important is that Wolbachia-infected mosquitoes become resistant to the parasite Plasmodium falciparum, which causes some 219 million cases of malaria worldwide and more than 660,000 deaths [1]. Wouldn’t it be amazing if Wolbachia-infected mosquitoes blocked the transmission of malaria?

Unfortunately, Wolbachia don’t normally pass from generation to generation in Anopheles, the mosquitoes that spread malaria. But that hurdle has now been overcome. Continue reading