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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Snapshots of Life: Neurons in a New Light

Mouse Midbrain

Credit: Michael Shribak, Marine Biological Laboratory, Woods Hole, MA

Birds do it, bees do it, and even educated fleas do it. No, not fall in love, as the late Ella Fitzgerald so famously sang. Birds and insects can see polarized light—that is, light waves transmitted in a single directional plane—in ways that provides them with a far more colorful and detailed view of the world than is possible with the human eye.

Still, thanks to innovations in microscope technology, scientists have been able to tap into the power of polarized light vision to explore the inner workings of many complex biological systems, including the brain. In this image, researchers used a recently developed polarized light microscope to trace the spatial orientation of neurons in a thin section of the mouse midbrain. Neurons that stretch horizontally appear green, while those oriented at a 45-degree angle are pinkish-red and those at 225 degrees are purplish-blue. What’s amazing is that these colors don’t involve staining or tagging the cells with fluorescent markers: the colors are generated strictly from the light interacting with the physical orientation of each neuron.

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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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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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Malaria Vaccine Shows Promise

Malaria has confounded biomedical researchers for decades because it’s been impossible so far to develop a vaccine that offers a high level of protection. But, thanks to a different approach to vaccine design and delivery, there’s hope that we may have finally turned the corner in the fight against this mosquito-borne health threat. Continue reading