Thursday, August 21, 2014

How lizards regenerate their tails: Researchers discover genetic 'recipe

By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers from Arizona State University is one step closer to solving that mystery. The scientists have discovered the genetic "recipe" for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.An interdisciplinary team of scientists used next-generation molecular and computer analysis tools to examine the genes turned on in tail regeneration. The team studied the regenerating tail of the green anole lizard (Anolis carolinensis), which when caught by a predator, can lose its tail and then grow it back.
"Lizards basically share the same toolbox of genes as humans," said lead author Kenro Kusumi, professor in ASU's School of Life Sciences and associate dean in the College of Liberal Arts and Sciences. "Lizards are the most closely-related animals to humans that can regenerate entire appendages. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing."
Other animals, such as salamanders, frog tadpoles and fish, can also regenerate their tails, with growth mostly at the tip. During tail regeneration, they all turn on genes in what is called the 'Wnt pathway' -- a process that is required to control stem cells in many organs such as the brain, hair follicles and blood vessels. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.
"Regeneration is not an instant process," said Elizabeth Hutchins, a graduate student in ASU's molecular and cellular biology program and co-author of the paper. "In fact, it takes lizards more than 60 days to regenerate a functional tail. Lizards form a complex regenerating structure with cells growing into tissues at a number of sites along the tail."

"We have identified one type of cell that is important for tissue regeneration," said Jeanne Wilson-Rawls, co-author and associate professor with ASU's School of Life Sciences. "Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues."
"Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail," said Kusumi. "By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future."
The researchers hope their findings will help lead to discoveries of new therapeutic approaches to spinal cord injuries, repairing birth defects, and treating diseases such as arthritis.The research team included Kusumi, Hutchins, Wilson-Rawls, Alan Rawls, and Dale DeNardo from ASU School of Life Sciences, Rebecca Fisher from ASU School of Life Sciences and the University of Arizona College of Medicine Phoenix, Matthew Huentelman from the Translational Genomic Research Institute, and Juli Wade from Michigan State University. This research was funded by grants from the National Institutes of Health and Arizona Biomedical Research Commission.

Keerti Mishra
Faculty Of Biotechnology

Wednesday, August 13, 2014

When Will We Have a Vaccine for Ebola Virus?

The deadly Ebola outbreak in west Africa highlights the urgent need for a vaccine, and researchers say one may be available in a few years

Source: Scientific American
The latest outbreak of Ebola virus in west Africa is the worst ever—as of Monday, it had infected more than 1,200 people and claimed at least 672 victims since this spring. Guinea, Liberia and Sierra Leone all have confirmed cases. An official at Doctors Without Borders has declared the outbreak as “totally out of control,” according to NBC News. Unfortunately, doctors have no effective vaccines or therapies. Health care workers can only attempt to support patients’ immune systems (regulating fluids, oxygen levels, blood pressure and treating other infections) to help the afflicted fight off the virus as best they can.
A vaccine to help battle future Ebola outbreaks may be just a few years away, however. During the past decade researchers have made significant progress, and vaccines have worked in nonhuman primates. But it has been hard to raise money for human safety tests. To learn about the latest advances as well as obstacles, Scientific American spoke to Thomas Geisbert, a virologist in the Department of Microbiology and Immunology at The University of Texas Medical Branch at Galveston. He’s studied the Ebola virus since 1988 and is currently involved in vaccine research and development.

 Are there any promising vaccines in development for the Ebola virus?
There are quite a few preventative vaccines in development, with three to five that have been shown to completely protect nonhuman primates against Ebola. Some of these vaccines require three injections or more and some require just a single injection. Most of them are being funded by the U.S. government, so they’re in various stages of development, but none of them are  licensed.

The hang-up point with these vaccines is the phase I trials in humans. That’s where scientists get frustrated because we know these vaccines protect animals and we don’t quite understand the regulatory process of why things can’t move faster. I can’t give you an answer as to why it’s taking so long.

Why doesn’t the human immune system fight the virus off?
The Ebola virus is usually transmitted by close contact and the first cells it affects are cells important to your primary immune response—monocytes, macrophages and dendritic cells. These cells are important because they’re the first to recognize that something foreign has entered your body and the first cells to trigger your innate immune system to fight off the infection. This makes it hard to mount an effective immune response against the virus—your body has a tough time fighting the virus off, and the virus multiplies to the point that it takes over major organs in your body.
I’ll give you an example of how a vaccine might work. The vaccine VSV is probably one of the most promising, and it’s based on a viral vector related to the rabies virus. It’s a bullet-shaped particle, and on its surface is a structural protein called a “glycoprotein,” which allows a virus to recognize a host cell, bind to it and take over the host cell’s machinery. With a vaccine, we remove the gene that encodes the glycoprotein of the VSV virus and we replace it with a gene that encodes the glycoprotein of Ebola. You end up with a vaccine that has an Ebola glycoprotein on the surface. Now, it doesn’t behave like Ebola because the rest of its genome is not Ebola, but because it has the Ebola glycoprotein your body is going to recognize it as foreign and build up an immune response against Ebola.

How far along in development is the VSV vaccine?
It’s at the point now where we’re trying to get the funds to do the human studies.
What are the biological challenges of developing a vaccine for Ebola?
There are some vaccines that are “replication defective,” meaning they don’t replicate, and they tend to be safer. Then there are other vaccines that are more efficacious, but they’re “replication competent.” An example of the latter would be the measles vaccine or yellow fever vaccine. They’re usually crippled, so they’re not as dangerous as a wild type virus but certain people could have an adverse event when given a vaccine that’s replication competent.

Replication-competent vaccines may only require a single injection whereas with the replication-defective vaccines you might have to get boosters every year, because they’re not as efficient. So do you go for a vaccine that protects humans in a single injection? In Africa you almost have to, because in an area like that you’re lucky to get someone into a clinic to be vaccinated once. It’s a trade-off—efficacy versus safety. That’s one of the biggest challenges.
Can you give an estimate for when we might have an effective Ebola virus vaccine?
My guess is anywhere from two to six years. I hate to say this, but it really depends on financial support for the small companies that develop these vaccines. Human studies are expensive and require a lot of government dollars.
I would like to see a situation where we tried to advance our lead candidate vaccines as fast as we can to get phase I studies done. I think we should start with the first responders—the health care workers in areas of high risk. This outbreak is so unique because it’s occurring in an area we’ve never seen it before and also because it seems there’s a higher percentage of medical staff infected than we’ve seen before. I’ve seen all of these vaccines work in numerous animals and I’ve never seen an adverse event from them. I appreciate the safety concerns but it would be great if there were some way to fast-track this. People are being exposed to Ebola and there’s a 60 to 90 percent chance they’re going to die—I think we have to look at it in this context.
Faculty of Bii

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