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inoki genome fight 3 PROMO
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inoki genome fight 3 PROMO - Video

INOKI GENOME FIGHT 3
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INOKI GENOME FIGHT 3 - Video

GENOME THERAPY | SPEED ART
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GENOME THERAPY | SPEED ART - Video

UMMS scientists seek ways to use powerful gene editing tool to excise latent HIV virus

VIDEO:Scot Wolfe, Ph.D., associate professor of molecular, cell and cancer biology, and Jeremy Luban, M.D., the David J. Freelander Professor in AIDS Research and professor of molecular medicine at UMass... view more

WORCESTER, MA -The virus that causes AIDS is an efficient and crafty retrovirus. Once HIV inserts its DNA into the genome of its host cells, it has a long incubation period, and can remain dormant and hidden for years. And while physicians can mix and match a cocktail from a host of antiretroviral drugs to keep the virus in check, the virus can reactivate if treatment is stopped.

In an attempt to render latent HIV completely harmless, researchers at the University of Massachusetts Medical School are using Cas9/CRISPR, a powerful gene editing tool, to develop a novel technology that can potentially cut the DNA of the latent virus out of an infected cell.

"On the simplest level we're employing a very precise pair of scissors to go in and clip out all, or part of, the HIV genome and reattached the severed ends of the human genome," said principal co-investigator Scot Wolfe, PhD, associate professor of molecular, cell and cancer biology at UMass Medical School. "If we could do that, the hope is that this would be a step on the road to getting a functional cure for HIV."

A component of the immune system found in normal bacteria, in its natural state CRISPR protects bacteria from viral invasion. Since its discovery, researchers have been furiously finding ways to program this system to quickly and selectively edit specific genetic sequences for study.

For all its versatility, applications for the CRISPR system remain confined to the lab. Despite recent advances showing that Cas9/CRISPR can edit HIV from an infected cell in culture, this technique remains too imprecise to be used clinically because of its tendency to cut into random regions of the genome, producing deleterious, off-target effects.

To improve the fidelity and precision of the Cas9/CRISPR gene editing system for this project, Wolfe has proposed fusing it with an additional domain that improves its specificity. This would conceivably allow the CRISPR system to edit out only the HIV DNA without the potential for stray cuts in the human genome.

The other hurdle to using current Cas9/CRISPR technology against HIV is that while researchers have some notions where the virus might be hiding, they still don't know how to find the virus in latently infected cells.

"Cells that are infected with HIV are permanent carriers of the viral genome. They are a kind of time bomb that can reactive at any time if a patient stops taking their antiretroviral treatment," said principal co-investigator Jeremy Luban, MD, the David J. Freelander Professor in AIDS Research and professor of molecular medicine at UMass Medical School. "In order to attack the virus in its latent state, we really need to understand where the virus lives and what it needs to survive."

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Editing HIV out of our genome with CRISPR

Gorilla Doctors/UC Davis

Mountains gorillas live in two isolated populations in Central Africa.

Kaboko, a mountain gorilla, had a rough start in life: in 2007, the three-year-old orphan was caught in a poachers snare in the Democratic Republic of the Congo. Rescuers, who were forced to amputate his hand to treat his injuries, gave him a name that means one missing an arm in a local language.

Kaboko died in 2012, but his DNA lives on. Researchers have used genetic information from him and six other animals to construct the first complete genomic sequence for the mountain gorilla (Gorilla beringei beringei), which they report in Science along with the genome of the closely related eastern lowland gorilla (Gorilla beringei graueri)1. The data may help conservationists to improve the plight of the critically endangered mountain gorilla, which is found only in Central Africa.

The genomes reveal that the genetic diversity of both subspecies has been declining for 100,000 years. That is surprising, says Ajit Varki, a molecular biologist at the University of California, San Diego. You have animals that have no predators and easy sources of food in a way they have everything going for them and yet they have been heavily pressured, he says. Some of that pressure is probably attributable to natural changes in the extent of Central Africa's forests, and some to the emergence of humans, but Varki says the relative balance of these factors in the distant past is hard to determine.

The more recent impact of humans is clear. Heavy hunting caused the gorilla population to drop to fewer than 300 animals by the 1970s2. The number has since risen to more than 800, thanks to conservation efforts promoted by primate researchers such as Dian Fossey.

Still, the latest study reveals that genetic diversity of eastern gorillas remains low. The paired chromosomes of an individual mountain gorilla typically have the same DNA sequence for 34.5% of their length. The figure in eastern lowland gorillas is even higher, at 38.4%. Both subspecies have much lower genetic diversity than the western gorilla (Gorilla gorilla, 13.8% shared sequence) and even the children of human parents who are first cousins (11%)3.

The gorilla is not the first non-human primate to have its complete genome sequenced that was the chimpanzee (Pan troglodytes), in 20054. But mountain gorillas were among the most difficult primates to study. Unlike other great apes, no mountain gorillas live in captivity. In the wild, the animals are found in only two places: the Virunga Volcano Massif and the Bwindi Impenetrable Forest, two habitats some 30 kilometres apart that straddle the Democratic Republic of the Congo, Rwanda and Uganda.

Researchers spent six years waiting for permission to study mountain-gorilla blood samples collected by the charity Gorilla Doctors, which treats injured wild gorillas. The delay was caused by the strict paperwork required by the Convention on International Trade in Endangered Species of Wild Fauna and Flora, a treaty that governs the flow of such materials.

But that long wait did have some benefits. Technology and our knowledge of genomics were getting better during all that time, says Peter Sudmant, a geneticist at the University of Washington in Seattle and a co-author of the study. As a result, the mountain-gorilla genome is of higher quality than previously published genomes of other gorilla subspecies.

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Mountain gorillas stuck in genetic bottleneck

IMAGE:A dogwood tree shows off its flowers on the University of Georgia campus. view more

Credit: Peter Frey/University of Georgia

Athens, Ga. - The flowering dogwood tree is associated with the beginning of spring throughout much of the U.S. Now, thanks in part to a $1.4 million grant from the National Science Foundation, a group of researchers from universities across the Southeast have joined forces to understand the genetics of this iconic tree.

Their Dogwood Genome Project will create the first complete genome sequence for dogwoods, ultimately enabling plant breeders to use genetic markers to guide cultivation of new varieties that are as beautiful as they are strong.

For their project to be a success, the researchers will have to collect a lot of data, and they're asking dogwood lovers and science enthusiasts to help. The Dogwood Genome Project has teamed with the National Phenology Network, a collection of more than 6,000 citizen scientists across the U.S. who track the seasonal changes in plants throughout the year and share their findings through the Nature's Notebook website.

"Dogwoods are one of the most popular ornamental trees in the country, but we don't know a lot about its genetic makeup," said Jim Leebens-Mack, the project leader and associate professor of plant biology at the University of Georgia. "Once we unlock the genome and begin comparing different varieties and species of dogwood, we can help speed breeding of trees that have varied flowering times, different colored petals and the ability to resist devastating diseases."

Nature's Notebook provides all the instruction and tools an observer needs to participate. Once registered, participants can help scientists by tracking native flowering dogwoods in their own community. The information gathered will help researchers identify the genetic and environmental influences that give trees certain traits.

"We know there are a lot of plant lovers out there, and this is a great opportunity for them to share their passion and make a really meaningful contribution to science," said Leebens-Mack, who is also director of the Georgia Genomics Facility and a member of the Plant Center at UGA.

In the meantime, the research team, which includes scientists from UGA, the University of Tennessee and North Carolina State University, will begin their work by sequencing the genome of a popular dogwood variety commonly known as Appalachian Spring. This genome will serve as a reference for the team to compare with sequences from other dogwood varieties as well as trees sampled from natural populations.

These comparisons will yield information on the genetic basis of differences in flowering time, flower color and susceptibility to disease. Horticulturists will also use the genome data to guide their breeding programs and produce more beautiful and robust dogwoods.

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Every dogwood has its day: Dogwood Genome Project calls on citizen scientists for help