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A Scientist’s Exploration of Regeneration

Wed, 2019-07-17 09:10
Viravuth (“Voot”) Yin, associate professor of regenerative biology and medicine at MDI Biological Laboratory and chief scientific officer at Novo Biosciences, Inc., in Bar Harbor, Maine. Credit: MDI Biological Laboratory.

In 1980, a week after his 6th birthday, Viravuth (“Voot”) Yin immigrated with his mother, grandfather, and three siblings from Cambodia to the United States. Everything they owned fit into a single, 18-inch carry-on bag. They had to build new lives from almost nothing. So, it’s perhaps fitting that Yin studies regeneration, the fascinating ability of some animals, such as salamanders, sea stars, and zebrafish, to regrow damaged body parts, essentially from scratch.

Yin’s path wasn’t always smooth. His family settled in Hartford, Connecticut, near an uncle who had been granted asylum during the Vietnam War. Yin got into a lot of trouble in school, trying to learn a new culture and fit in. Things improved when his mother moved him and his siblings to West Hartford, well known for its strong schools.

Soon, he was off to Bates College in Maine, where he hoped to become a successful novelist. But fate stepped in during his sophomore year when the creative writing class he’d hoped to take was full. A class on molecular biology was available and fit into his schedule.

“I took it, and it really opened the world to me because I suddenly realized you could do all of these remarkable things with DNA. You could turn things on, turn things off. You could perturb the system and see what happens,” he says. “From that point on, there was a road laid out in front of me. The more that I dove into science, the more the road was seemingly paved for me.”

That path led Yin to a bachelor’s degree in biology. He even spent two summers working as an intern at New England Biolabs, a biosciences company in Ipswich, Massachusetts. He was sold on the idea of running his own lab someday, to harness the power of genetics and understand how biology works from the ground up. But first he needed to learn genetics and how to use animal models to study basic biology. For that, he chose to study with geneticist Carl Thummel at the University of Utah in Salt Lake City.

Thummel studies Drosophila, a fruit fly found in research labs around the world. Yin’s research examined how Drosophila transform from larvae to adults. A single hormone triggers both the destruction of the larva’s tissue and the growth of the adult’s tissue. Yin examined how this complex process works at the genetic level.

Credit: MDI Biological Laboratory.

The experience taught Yin the skills he’d need to study a similar process: regeneration. Fruit flies can’t regenerate, so Yin shifted to an animal that can. He chose zebrafish, a small freshwater minnow. Zebrafish can regrow their fins and even repair a damaged heart, brain, or spinal column. Yin moved from Utah to Ken Poss’ lab at Duke University School of Medicine in Durham, North Carolina, where he completed his Ph.D.

While at Duke, Yin tried a new technique to study gene regulation using micro RNAs (miRNAs). miRNAs are small pieces of RNA that control which genes are turned on and off in cells. The technique was so new that Poss cautioned Yin about trying it.

“I have a tendency of being a little bit stubborn, so I said, ‘I’m going to do it anyway,’” recalls Yin. “I thought: If I’m going to fail, I’m going to do it in a spectacular fashion.”

That decision put him on a path to success that he’s been on ever since. In his own lab in Maine, Yin leverages what he learned at Duke. He’s begun to piece together the genetic pieces and processes that control regeneration. By studying zebrafish, salamanders, and a ray-finned fish from Africa called the bichir, he’s identified several miRNAs that are important for coordinating regeneration. He’s also found similar genetic mechanisms in animals with modest regenerative abilities, such as mice and humans. These and other findings suggest that humans possess the molecular processes needed for regeneration.

“The critical difference is that, unlike the zebrafish, humans don’t activate these processes in response to an injury,” says Yin.  

To continue to identify the mechanisms necessary for regeneration and to encourage more research in this area, Yin and his University of Maine colleague Benjamin King have created RegenDbase , a database of comparative models of regeneration.

Perhaps most promising of all is the work in Yin’s lab on a small molecule called MSI-1436. This molecule appears to jump-start regeneration in zebrafish and in adult mice. Earlier research by others found that newborn mice retained the ability to repair heart damage for 1 week after birth. This suggests that the mechanisms are there in adults, but just dormant. Yin’s team gave MSI-1436 to adult mice with heart damage. Amazingly, their scar tissue shrank, new heart muscle formed, and heart function increased nearly twofold. This finding holds promise that MSI-1436 might someday help repair damage from heart attacks in humans. In fact, the MDI Biological Laboratory has spun off a private company, Novo Biosciences, that hopes to test this compound, now called trodusquemine, in humans.

Novo Biosciences is also testing trodusquemine for its ability to slow the degeneration of heart and skeletal muscle in a mouse model of Duchenne muscular dystrophy. Additionally, the company plans to test the molecule in a mouse model of human diabetic kidney disease to investigate whether it can repair damaged kidneys.

Yin hasn’t written his novel—yet. But from his early days in the United States rebuilding his life from scratch, he has used his innate determination to find answers to some of life’s most difficult questions. And his research on how animals rebuild body parts from damaged tissue may turn out to be a best-selling story yet.

Yin’s research and RegenDbase are supported in part by NIGMS under grant numbers P20GM103423 and P20GM104318.

Cilia: Tiny Cell Structures With Mighty Functions

Wed, 2019-07-03 09:39
Credit: Zvonimir Dogic, Brandeis University.

Imagine an army of tiny soldiers stationed throughout your body, lining cells from your brain to every major organ system. Rather than standing at attention, this tiny force sweeps back and forth thousands of times a minute. Their synchronized action helps move debris along the ranks to the nearest opening. Other soldiers stand as sentries, detecting changes in your environment, relaying that information to your brain, and boosting your senses of taste, smell, sight, and hearing.

Your brain may be the commander in chief, but these rank-and-file soldiers are made up of microscopic cell structures called cilia (cilium in singular).

Here we describe these tiny but mighty cell structures in action.

Brain

The brain has ridges, peaks, and valleys with areas of open space in between, and cilia line those open spaces, helping to move fluid around the different brain regions. Scientists believe these cilia also have a function beyond simply transporting fluid and may help the brain interpret how the body is feeling, including sensing hunger. Someday, these cilia might even be a target for therapies, such as curbing appetite to help with weight loss.

Eyes

Cilia in the eye’s retina help convert light into electrical signals that are then sent to the brain. The brain sorts through these light signals, packages them, and transforms them into the images we can see. Cilia damage in the eye can lead to vision loss.

Ears

Cilia in the ear can have a variety of functions. One type of cilia helps with hearing and detecting sound. They capture sound signals and then send them to your brain for processing, which is why cilia damage in the ear can lead to significant hearing loss. Cilia also help to clear your ear of wax buildup, moving the wax through the inner parts of the ear to keep your ear canal open. Finally, these little hairs can act as motion sensors, monitoring the fluid in the ear to help the brain maintain its sense of balance.

Nose

Like the cilia in your eyes and ears, the little hairs that line the cells in the nose help you interpret the world around you. These tiny hairs wave back and forth, pulling in odor molecules and sending them to the brain for processing. Cilia also aid in moving dust and mucous out of your body, sweeping them from your nose down through the throat and the rest of the GI tract, where they can be flushed out of your system.

Tongue

Cilia on the cells in the tongue help the brain detect different tastes. These tongue cilia partner with ones in the nose, gathering information from food and relaying it to the brain to interpret specific tastes, such as sweet, salty, bitter, or bland.

Lungs and Airways

Like tiny brooms, cilia sweep mucus, bacteria, and dust particles from your lungs and airways toward your throat and out of your body. These tiny sweepers are vital for keeping you breathing easy. Diseases can injure cilia, preventing them from removing dust and allergens from your airways. And that can lead to sinusitis, a painful condition marked by a buildup in mucus, swollen nasal passages, and a chronically runny nose.

Heart

Cilia’s ability to sweep and clean is particularly evident in the heart. Researchers looking at mice hearts have found that cilia are especially dense in areas where blood vessels come together or curve. Scientists believe the cilia in these spaces help to keep those vessels open and free from the buildup of plaque, a disease called atherosclerosis.

Kidneys

Important to kidney function, cilia monitor the flow of urine in this pair of organs. For nearly a decade, scientists have looked for a link between kidney disease and cilia. Although the exact mechanism isn’t clear, researchers believe that kidney cilia become damaged and unable to monitor urine flow, causing the kidneys to become scarred and diseased, leading to kidney failure.

Prostate

Though the precise function is unknown, scientists believe that cilia are linked to cancer in several organs, including the prostate, an essential part of the male reproductive system. The prostate helps make the fluid (semen) that cushions and protects sperm cells. In examining cancerous prostate cells, one group of researchers found that diseased cells have fewer cilia, a condition that has been tied to the development of cancer tumors.

Reproductive Organs

In the female reproductive system, cilia help move the egg along the fallopian tube where it can be fertilized. Likewise, in the male reproductive system, cilia help power sperm. Each sperm cell has a type of cilium called a flagellum that propels it along the fallopian tube. That whipping tail action, coupled with the cilia on the cells lining the tube, help ensure that egg and sperm meet at precisely the right place at the right time.

Muscles

When muscles are injured, or as we grow older, fat cells often replace muscle cells. Those fat cells have an abundance of cilia, which are known to speed this muscle-to-fat breakdown. Scientists are looking at ways to genetically disable cilia in an effort to block muscle conversion to fat, keeping muscles in tip-top shape and aiding the body in coming back from injury.

Some of the research mentioned in this post was funded in part by NIGMS under grant number R01GM095941.

Don’t Be Afraid to Search in the Dark: Jon Lorsch Encourages Graduates to Consider New Perspectives

Wed, 2019-06-19 09:36

Jon Lorsch, from Swarthmore College’s class of 1990, returned to his alma mater in May to accept an honorary Doctor of Sciences degree for his accomplishments as a biochemist and his visionary leadership of NIGMS. During the university’s 147th commencement, he spoke to the 2019 graduating class, offering advice and examples of how we can look for opportunities in the least likely places.

Watch the 5-minute video to hear Lorsch’s advice to the graduates—and all future scientists—to venture into the unknown in search of the next big advance in biomedical research.

Transcript of Lorsch’s Speech:

In his famous “This Is Water” speech at Kenyon College, David Foster Wallace noted that “the deployment of didactic little parable-ish stories” has become “a requirement of U.S. commencement speeches.” 

So, apologies if you’ve already heard this one.

A man is walking down the street at night. He sees another man on his hands and knees under a streetlight, apparently looking for something. The first man asks the second what he’s looking for and the second man replies, “My car keys.” So the first man offers to help, and together they crawl around on the ground under the streetlight searching for the lost keys. After a long time, the first man says to the second, “I’m pretty sure they aren’t here. Are you sure this is where you lost them?” The second man says, “No, but this is the only place there’s enough light to look for them.”

This story is even less funny than the fish story that Foster Wallace told at Kenyon, but, like his parable, it’s one I find myself coming back to again and again.

So here’s the point: Most of the time, we are the second man.

I’m a recovering academic, so let me use that world as a frame of reference. If you are going to graduate school from here—and this being Swarthmore, you probably are—you are going to work on something closely related to your advisor’s area of expertise. Once you get your Ph.D., you may do a postdoctoral fellowship, where you will again work on something close to what your advisor works on. Finally, when you strike off on your own, the system tends to expect that you’ll keep working on what you did as a postdoc, lest you take on something that is too risky and that is out of your wheelhouse.

In other words, you will be studying the ground under the streetlight.

I’ve become convinced that we could make much faster progress if more people were brave enough—or, perhaps, defiant enough—to go off into the darkness.
 
Consider the following recent examples of moving away from the streetlights in biomedical research:
 
The African spiny mouse. Why in the world would anyone study the African spiny mouse? Well, it turns out that these small rodents can do something no other mammal is known to do: completely regenerate damaged tissue without forming a scar. What have they figured out that the rest of their mammalian cousins, including us, haven’t? If we can learn their secrets, it could have profound implications for medicine. We might be able to find better ways to repair burns and other severe wounds, good as new. And maybe even to mend damaged heart tissue after a heart attack. Because someone moved out from under the streetlight to study the African spiny mouse, this science fiction might someday become reality.
 
Example two: Why would any self-respecting modern molecular biologist risk her career studying Gila monsters? Those prehistoric-looking, poisonous lizards that dwell in the American Southwest? Well, it turns out that there is now an FDA-approved drug for Type 2 diabetes that is derived from a component of Gila monster venom, all because someone made that choice. Gila monsters don’t dwell under streetlights.
 
And here’s a biological puzzle that as far as I can tell is still out in the darkness. Maybe one of you graduates might solve it for me. And this is for real. I’ve been worrying about this for at least 10 years.
 
Why is it that every known class of organism is extensively preyed upon by free-floating viruses, except, it appears, for one: fungi? Hundreds of different viruses infect us and other mammals. It is estimated that there are more bacteriophage—that is, viruses that prey on bacteria—than all other organisms on earth. There are even giant viruses that infect amoebas. But free-floating viruses that infect fungi appear to be extremely rare. Have fungi figured out something that no other organism knows? If so, I think we need to know it. Or are we just missing a huge swath of biology—infectious fungal viruses—because we haven’t gotten out from under the streetlight to search for it in the darkness?
 
My assertion that progress in science would be accelerated if more researchers ventured into the darkness is probably true of other fields as well. Certainly, both artists and entrepreneurs do best away from the streetlights. But there are admittedly limits to this thesis. For example, I would advise acrobats, airline pilots, and electricians to stay away from the dark places of the theory and practice of their professions.
 
Class of 2019, I urge most of you to explore the darkness. And then come back and tell us what you find there. May all of your journeys be exciting and rewarding.

*This post was derived with permission from Swarthmore College .

Computational Biologist Melissa Wilson on Sex Chromosomes, Gila Monsters, and Career Advice

Thu, 2019-06-06 07:14
Dr. Melissa Wilson.
Credit: Chia-Chi Charlie Chang.

The X and Y chromosomes, also known as sex chromosomes, differ greatly from each other. But in two regions, they are practically identical, said Melissa Wilson , assistant professor of genomics, evolution, and bioinformatics at Arizona State University.

“We’re interested in studying how the process of evolution shaped the X and the Y chromosome in gene content and expression and how that subsequently affects literally everything else that comes with being a human,” she said at the April 10 NIGMS Director’s Early-Career Investigator (ECI) Lecture at NIH.

In humans, each cell contains 23 pairs of chromosomes, for a total of 46. The first 22 pairs look the same in both males and females. The last pair, the sex chromosomes, differ. Typically, females have two X chromosomes, while males have one X and one Y chromosome.

“I say ‘typically’ because I don’t know which one of us is normal, and I don’t like saying something is normal,” she said. “Variations in the sex chromosomes can be pretty typical.”

Historically, most clinical research was conducted in men, she noted. “We’re finding out that treatments designed for men don’t work so well in women.” There is, however, a massive sex difference.

The sex chromosomes have been evolving over the past 200 million years, she explained. At first, the chromosomes were identical. Over time, the Y chromosome started to break and rearrange itself. These inversions made it more difficult to recombine with the X chromosome. Now, the X chromosome has about 1,100 genes while the Y chromosome has just 27 unique genes.

And yet there are two regions called pseudoautosomal regions (PAR1 and PAR2) on the tips of the sex chromosomes that can pair with each other and swap DNA. This is called recombination. Wilson said a sex-determining gene called SRY sits near the boundary of the regions on the Y chromosome. Individuals who inherited the Y chromosome “went on to make testes and those who didn’t made eggs.” In some cases, SRY can transfer to the X chromosome.

A deficiency in PAR1 recombination has been linked to Klinefelter syndrome, a genetic condition where males are born with an extra X chromosome. This occurs in about 1 out of every 500 births in the U.S.

NIGMS Director Jon Lorsch (front, second from left) and Wilson gather with college students after the ECI lecture. Credit: Chia-Chi Charlie Chang.

There are other sex-linked disorders besides Klinefelter syndrome. One, called Turner syndrome, happens in about 1 in 2,000 or 2,500 females. Those born with the condition have one missing or structurally altered X chromosome. Another is de la Chapelle syndrome, a rare disorder in which individuals have two X chromosomes but have a male appearance.

Wilson said the field needs to develop new methodologies to analyze the sex chromosomes, recognizing the complications and appreciating the variations.

Wilson’s lab is also studying the Gila monster’s genome. A black-and-orange lizard native to the southwestern United States and Mexico, Gila monsters have venomous saliva. There’s a peptide in the venom that’s used to treat type 2 diabetes.

“We’d like to understand what the peptide is doing in the monsters and then can better understand how it works in humans,” Wilson said.

Her lecture was followed by a Q&A chat with NIGMS Director Jon Lorsch.

Cover of Pathways student magazine, which includes an interview with Wilson.

Wilson asserted, “You’re not going to be able to do biology without understanding programming in the future,” adding that scientists don’t have to be expert programmers, but they must understand it.

She credited her scientific success to diligence, good luck, and mentors who made sure she had opportunities and built her confidence.

In her lab, Wilson talks about the challenges of research with her students. It’s important for them to hear different perspectives and realize that “we’re here because we don’t know the answer yet” and that being wrong can still lead to interesting data.

Recently, Wilson was featured in Pathways  student magazine, a collaboration between NIGMS and Scholastic, Inc. She called the experience “the coolest thing ever” to get to “be in Scholastic.”

Eric Bock is a staff writer for the NIH Record, a bimonthly general-audience publication for NIH employees.

*This post was derived with permission from the article, “Sex Chromosomes Can Trade DNA in Two Regions,” which originally appeared in the May 31, 2019, issue of the NIH Record.

Computational Biologist Melissa Wilson on Sex Chromosomes, Gila Monsters, and Career Advice

Wed, 2019-06-05 10:45
Dr. Melissa Wilson.
Credit: Chia-Chi Charlie Chang.

The X and Y chromosomes, also known as sex chromosomes, differ greatly from each other. But in two regions, they are practically identical, said Melissa Wilson , assistant professor of genomics, evolution, and bioinformatics at Arizona State University.

“We’re interested in studying how the process of evolution shaped the X and the Y chromosome in gene content and expression and how that subsequently affects literally everything else that comes with being a human,” she said at the April 10 NIGMS Director’s Early-Career Investigator (ECI) Lecture at NIH.

In humans, each cell contains 23 pairs of chromosomes, for a total of 46. The first 22 pairs look the same in both males and females. The last pair, the sex chromosomes, differ. Typically, females have two X chromosomes, while males have one X and one Y chromosome.

“I say ‘typically’ because I don’t know which one of us is normal, and I don’t like saying something is normal,” she said. “Variations in the sex chromosomes can be pretty typical.”

Historically, most clinical research was conducted in men, she noted. “We’re finding out that treatments designed for men don’t work so well in women.” There is, however, a massive sex difference.

The sex chromosomes have been evolving over the past 200 million years, she explained. At first, the chromosomes were identical. Over time, the Y chromosome started to break and rearrange itself. These inversions made it more difficult to recombine with the X chromosome. Now, the X chromosome has about 1,100 genes while the Y chromosome has just 27 unique genes.

And yet there are two regions called pseudoautosomal regions (PAR1 and PAR2) on the tips of the sex chromosomes that can pair with each other and swap DNA. This is called recombination. Wilson said a sex-determining gene called SRY sits near the boundary of the regions on the Y chromosome. Individuals who inherited the Y chromosome “went on to make testes and those who didn’t made eggs.” In some cases, SRY can transfer to the X chromosome.

A deficiency in PAR1 recombination has been linked to Klinefelter syndrome, a genetic condition where males are born with an extra X chromosome. This occurs in about 1 out of every 500 births in the U.S.

NIGMS Director Jon Lorsch (front, second from left) and Wilson gather with college students after the ECI lecture . Credit: Chia-Chi Charlie Chang.

There are other sex-linked disorders besides Klinefelter syndrome. One, called Turner syndrome, happens in about 1 in 2,000 or 2,500 females. Those born with the condition have one missing or structurally altered X chromosome. Another is de la Chapelle syndrome, a rare disorder in which individuals have two X chromosomes but have a male appearance.

Wilson said the field needs to develop new methodologies to analyze the sex chromosomes, recognizing the complications and appreciating the variations.

Wilson’s lab is also studying the Gila monster’s genome. A black-and-orange lizard native to the southwestern United States and Mexico, Gila monsters have venomous saliva. There’s a peptide in the venom that’s used to treat type 2 diabetes.

“We’d like to understand what the peptide is doing in the monsters and then can better understand how it works in humans,” Wilson said.

Her lecture was followed by a Q&A chat with NIGMS Director Jon Lorsch.

Cover of Pathways student magazine, which includes an interview with Wilson.

Wilson asserted, “You’re not going to be able to do biology without understanding programming in the future,” adding that scientists don’t have to be expert programmers, but they must understand it.

She credited her scientific success to diligence, good luck, and mentors who made sure she had opportunities and built her confidence.

In her lab, Wilson talks about the challenges of research with her students. It’s important for them to hear different perspectives and realize that “we’re here because we don’t know the answer yet” and that being wrong can still lead to interesting data.

Recently, Wilson was featured in Pathways  student magazine, a collaboration between NIGMS and Scholastic, Inc. She called the experience “the coolest thing ever” to get to “be in Scholastic.”

Eric Bock is a staff writer for the NIH Record, a bimonthly general-audience publication for NIH employees.

*This post was derived with permission from the article, “Sex Chromosomes Can Trade DNA in Two Regions,” which originally appeared in the May 31, 2019, issue of the NIH Record.

Amazing Organisms and the Lessons They Can Teach Us

Wed, 2019-05-15 09:33

What do you have in common with rodents, birds, and reptiles? A lot more than you might think. These creatures have organs and body systems very similar to our own: a skeleton, digestive tract, brain, nervous system, heart, network of blood vessels, and more. Even so-called “simple” organisms such as insects and worms use essentially the same genetic and molecular pathways we do. Studying these organisms provides a deeper understanding of human biology in health and disease, and makes possible new ways to prevent, diagnose, and treat a wide range of conditions.

Historically, scientists have relied on a few key organisms, including bacteria, fruit flies, rats, and mice, to study the basic life processes that run bodily functions. In recent years, scientists have begun to add other organisms to their toolkits. Many of these newer research organisms are particularly well suited for a specific type of investigation. For example, the small, freshwater zebrafish grows quickly and has transparent embryos and see-through eggs, making it ideal for examining how organs develop. Organisms such as flatworms, salamanders, and sea urchins can regrow whole limbs, suggesting they hold clues about how to improve wound healing and tissue regeneration in humans.

Here are profiles of other amazing organisms that are entering the research world.

Australian Zebra Finch

Credit: Chris Olson.

Whether it’s a robin, sparrow, or yellow-rumped warbler, each songbird sings its own tunes. For decades, scientists have studied how the birds learn their unique songs. Many researchers, including Claudio Mello  at the Oregon Health and Science University in Portland, study vocal learning in Australian zebra finches. These common birds sing a simple, easily analyzed tune. Mello and other scientists are identifying which genes and which parts of finch brains allow the birds to learn to sing their songs. Similar gene pathways and brain circuitry come into play when humans learn to speak. A better understanding of vocal learning in birds can shed light on how we acquire language and may help scientists and clinicians better address a broad range of speech and language disorders. For more information on finch-brain research, visit the NIGMS-funded ZEBrA website .

African Spiny Mice

Credit: Malcolm Maden, University of Florida.

If you’ve ever seriously cut or burned yourself, you probably ended up with a thick, stiff scar. Internal organs can be similarly scarred when damaged by a heart attack, car crash, or other trauma. Such scarring can make it hard for the organ to function and can even lead to death. Some scientists seeking ways to lessen or prevent dangerous scarring are beginning to study the African spiny mouse (Acomys kempi and Acomys percivali).

This mouse is the only mammal known to heal without scarring. Just like a lizard that can release then regrow a severed tail, the African spiny mouse can leave patches of its easily torn skin in a predator’s teeth, then regrow it later—healthy layers of skin that include hair follicles, sweat glands, fur, cartilage, blood vessels, and nerve fibers—all without any scar tissue.

Chelsey Simmons  at the University of Florida in Gainesville studies cells from these mice to figure out how they do it. By contributing to the understanding of how and why scar tissue forms—or doesn’t form—this research could reveal ways to prevent scarring caused by heart attacks, severe burns, and other injuries.

Hawaiian Bobtail Squid

Credit: Dr. Satoshi Shibata.

Antibiotic medications are usually excellent at killing bacteria. But some types of bacteria protect themselves by joining together by the hundreds and sometimes thousands into a cooperative community called a biofilm. The biofilm helps bacteria evade antibiotics.

Biofilms are common in almost any moist, relatively undisturbed location (your mouth, shower stalls, wastewater treatment centers). They can be extremely difficult to destroy. Although they play an important role in degrading organic matter and pollutants, they can wreak havoc in the human body. They can block narrow passages in medical stents and other implants. They can also cause recurrent, life-threatening infections in lungs, intestines, and other organs.

Strawberry-sized Hawaiian bobtail squid, found in the shallow waters around Hawaii, give scientists a chance to study how biofilms form inside the body of a host animal. These miniature squid have a mutually beneficial relationship with a type of biofilm-forming bacteria. The squid nourish and cultivate their bacterial partners, which form a biofilm and wait on the surface of a special organ. When needed, the bacteria leave their biofilm and enter the organ, where they provide the squid with a sort of invisibility cloak, hiding it from predators.

Researchers such as Karen Visick  at Loyola University in Chicago are studying this unique partnership between bobtail squid and their biofilm guests. They hope to gain a better understanding of how biofilms form, how they exist inside animals, and whether it’s possible to prevent, delay, or destroy them in humans.

Tasmanian Devil

Credit: iStock.

The Tasmanian devil, the world’s largest carnivorous marsupial, is in danger of extinction. In the past two decades, its population in the wild has plummeted by nearly 80 percent. One of the main causes is Tasmanian devil facial tumor disease. Animals with the disease develop tumors in and around their mouths. The tumors make it hard for the animals to eat, often leading to starvation.

The transmissible cancer is sweeping through Tasmanian devil populations. Researchers believe it spreads through the animals’ bite. When a healthy devil bites a diseased one, the resulting immune response leads to out-of-control cell growth and tumors. The disease kills more than 90 percent of animals that contract it.

Andrew Storfer  at Washington State University in Pullman is studying genes from the tumors and from some of the few animals that have contracted and recovered from the disease. His work suggests that some devils survive because key elements of their immune systems have evolved to resist the cancer. These studies are helping with cancer research in humans and are particularly applicable to cervical cancer, another transmissible cancer. The work is also uncovering strategies to help prevent the spread of disease among Tasmanian devils in the wild.

Arctic Ground Squirrel

Credit: Brian Barnes.

Our brains need a steady supply of blood and nutrients. When that flow stops, such as during a heart attack or stroke, it can damage or kill brain cells. More cells are damaged when blood flow restarts.

This isn’t the case for hibernating animals. Animals such as the Arctic ground squirrel can lower their body temperatures, heart rates, and blood flow for weeks at a time. And when they stop hibernating, these levels come back to normal without causing any damage.

Brian Barnes  and others at the University of Alaska in Fairbanks are studying these squirrels to see how their brains adapt to these changes, especially when their blood flow levels are low even when the squirrels aren’t hibernating. The work could help scientists learn new ways to prevent human brain damage that often occurs after a stroke.

Sea Lamprey

Credit: Jeramiah Smith.

Sea lampreys are parasitic fish that latch onto other fish using suction-type mouths. Lampreys then feed on the host’s blood and body fluids. Though harmful to other fish, these parasites have two traits that make them interesting research organisms. First, they can repair their spinal cords when injured, something most animals can’t do. Second, they’re able to streamline their DNA as they grow so that different cell types keep only the genes that are necessary to function and remove other genes that could be detrimental.

Lampreys were some of the first animals to evolve a backbone and other traits common to all vertebrates. Researchers are looking at this fish’s ancient genetic information to see what genes are essential in growing backbones and other characteristics, and how traits have been gained and lost along the way during evolution. Jeramiah Smith  at the University of Kentucky in Lexington studies these lost traits in hopes of finding new and unexpected ways of solving some of today’s most devastating human health problems, such as paralysis, cancer, and infertility.

Claudio Mello’s research is supported in part by NIGMS grant number 5R24GM12046402; Chelsey Simmons’ work is supported by 1R35GM1283101; Karen Visick’s work is supported by 1R01GM11428801; Andrew Storfer’s research is supported by 5R01GM12656302; Brian Barnes and colleagues’ research is supported by 5P20GM10339518 under the IDeA Networks of Biomedical Research Excellence program; and Jeramiah Smith’s work is supported by 1R35GM13034901.

PREP Scholar’s Passion for Understanding Body’s Defenses

Wed, 2019-04-24 10:02

Charmaine N. Nganje, PREP scholar at Tufts University in Boston.
Credit: Katherine Suarez.

Charmaine N. Nganje

Hometown: Montgomery Village, Maryland

Influential book : The Harry Potter series (not exactly influential, but they’re my favorite)

Favorite movie/TV show: The Pursuit of Happyness/The Flash

Languages: English (and a bit of Patois)

Unusual fact: I’m the biggest Philadelphia Eagles fan from Maryland that you’ll ever meet

Hobbies: Off-peak traveling

Q. Which NIGMS program are you involved with?

A. The Postbaccalaureate Research Education Program (PREP)  at the Sackler School of Graduate Biomedical Sciences at Tufts University in Boston.

Q. What got you interested in science?

A. I’ve always loved science. I loved being outside and had a natural curiosity to understand how things worked in and around us. I went to and participated in every science fair I could. I know I probably annoyed my mom with all my questions.

“Staining cells during lab almost felt like art class.”

After a rough sophomore year in college, I was starting to think science wasn’t the route for me anymore. Luckily, I enrolled in a microbiology class the following year, which sparked my interest in research and my curiosity for science. This class was both fun and intellectually stimulating. Staining cells during lab almost felt like art class.

After taking this course, I wanted to learn more about microbes, so I worked as an undergraduate researcher in the bacterial pathogenesis lab of my instructor, Dr. Mara Shainheit.

I was fortunate enough to pick a project based on my own interests. Our project involved studying the interactions between bacteria and their host. My mentor inspired me to pursue a career in research, specifically studying host pathogenesis, or how our bodies can do more harm than good in response to infections.

Q. What research are you currently conducting at Tufts University?

White blood cells called neutrophils protect our bodies from infection by recognizing and destroying disease-causing bacteria. In this microscopy image, a neutrophil (shown in violet) is ingesting MRSA (methicillin-resistant, Staphylococcus aureus) bacteria, shown in yellow.
Credit: National Institute of Allergy and Infectious Diseases.

A. I’m lucky that I’m able to continue studying infectious diseases and how the immune system responds to disease-causing bacteria. I’m working with two scientists, Dr. Joan Mecsas and Dr. John Leong, to understand why people become more susceptible to bacterial diseases as they get older.

I’m particularly interested in a type of white blood cell called a neutrophil, which acts as a sort of “first responder” in the immune system. There are billions of neutrophils circulating throughout our bodies, attempting to destroy the bacteria that make us sick. I’m interested in discovering how the antimicrobial functions of neutrophils change as we age.

Q. What are your future plans as you approach the end of PREP at Tufts?

A. I’m focused and determined to pursue a Ph.D. in immunology, and I’ve applied to graduate programs in the Boston area. Everything the PREP program has provided, including the mentorship, workshops, and career panels, have solidified my decision. The program has helped me build confidence and learn essential skills to become an independent scientist. In the future, I’d like to use the knowledge I’ve gained through studying host-pathogen interactions to develop and enhance therapeutics.

Q. What motivates you to continue in this field?

“As long as I’m contributing new knowledge, I’ll remain curious and excited every day.”

A. Research is hard. You work long hours and sometimes—most of the time—things don’t work as expected. I’ve always known that I wanted to help people, and that’s what motivates me. Every day at the bench or under the tissue culture hood helps paint a clearer picture of how our immune system defends us from countless pathogens. As long as I’m contributing new knowledge, I’ll remain curious and excited every day.

Chromosomally speaking, what do you know about sex? Take a quiz to find out.

Wed, 2019-04-03 10:11

Women have two X chromosomes (XX) and men have one X and one Y (XY), right? Not always, as you’ll learn from the quiz below. Men can be XX and women can be XY. And many other combinations of X and Y are possible.

NIGMS Director’s
Early-Career Investigator Lecture
Sex-Biased Genome Evolution

Melissa A. Wilson, Ph.D.
Arizona State University

Wednesday, April 10, 2019
10:00-11:30 a.m. ET

Lecture followed by Q&A session
Info on the ECI Lecture webpage

You can learn more by listening to the live stream of a talk, titled “Sex-Biased Genome Evolution,” at 10 a.m. ET on April 10. The speaker, Melissa A. Wilson, is a researcher at Arizona State University who uses high-performance computing, statistics, and comparative genomics to study the X and Y chromosomes.

Wilson’s 30-minute talk is geared for an undergraduate-level audience and will be followed by a Q&A session. We encourage you use the hashtag #ECILecture to live-tweet the event and submit questions during the Q&A session.

For more details about Wilson’s work, background, and upcoming event, visit our ECI Lecture webpage. A videocast of the talk will be available to view live and at a later date.

Until then, see how well you do on the quiz below.

    1.) Conditions that result from an atypical number of sex chromosomes are frequently diagnosed:
  • a) In infancy, because it’s unclear whether the baby is a girl or boy

    That’s the case for some people, but many others have normal sexual organs. Try a different answer.

  • b) At puberty, because sexual development doesn’t progress as expected

    This can happen, but it doesn’t always. Puberty can progress normally. Consider other answers.

  • c) During child-bearing years, because the person is infertile or has reduced fertility

    True in some cases, but it’s not the best answer. Try again.

  • d) At any time during a person’s life

    That’s it! The symptoms and severity of these conditions vary widely and are not always recognized. About a million people in the U.S. are estimated to have a sex chromosome number that’s atypical. Some people with these conditions don’t even know it!

    2.) Which of the following chromosomal configurations is never possible?
  • a) A woman with a missing X chromosome (X0)

    Nope. Women with only one X chromosome (X0) have Turner syndrome. Give it another shot.

  • b) A man with a missing X chromosome (0Y)

    You’re right! This genotype is fatal long before birth. The X chromosome contains many genes that are essential to life for both males and females.

  • c) An extra X chromosome (XXY)

    Actually, this is more common than you might think. It’s known as Klinefelter syndrome. It affects between 1 in 500 to 1,000 newborn males. Try again.

  • d) An extra Y chromosome (XYY)

    Sorry, wrong answer. The XYY genotype is estimated to occur in approximately 1 in 1,000 newborn boys.

    3.) All of the following are sex-linked conditions except…
  • a) Hemophilia A

    Hemophilia A, a blood-clotting disorder, is caused by alterations to a gene on the X chromosome. In most cases, boys inherit the condition from their mothers, who carry the altered gene but do not experience symptoms (typically, women are protected because they carry a fully functional version of the gene on their second X chromosome). In about 30 percent of cases, a spontaneous genetic change causes the condition.

  • b) Duchenne muscular dystrophy

    Duchenne muscular dystrophy is caused by an alteration of the dystrophin gene on the X chromosome. The condition, characterized by progressive muscle degeneration and weakness, is usually diagnosed during early childhood. Like most X-linked recessive traits, it primarily affects boys. Women act as carriers who pass the altered gene to their children.

  • c) Down syndrome

    You got it. Down syndrome, also called trisomy 21, results from an extra chromosome 21. All the other conditions are caused by genetic variations on the X chromosome.

  • d) Red-green color blindness

    Red-green color blindness affects up to 8 percent of men and 0.5 percent of women of northern European descent. The genes responsible for the most common, inherited color blindness are on the X chromosome. Women who have unaffected genes on their other X chromosome will not experience color blindness but can pass the altered genes to their children.

    4.) Today, the X chromosome in humans is much larger than the Y chromosome. Millions of years ago, these two sex chromosomes were the same size. What happened?
  • a) The original sex chromosomes were both as large as today’s X chromosome. Over time, the Y chromosome lost genes and shrunk.

    Yes, it’s true. Melissa Wilson will explain more in her April 10 talk. Join us by videocast live or later.

  • b) The original sex chromosomes were both as large as today’s Y chromosome. Two Y chromosomes got attached and were passed down that way, resulting in the larger X chromosome today.

    Although sometimes chromosomes (or parts of chromosomes) can stick to each other, that’s not what happened in the case of X and Y. Melissa Wilson will explain more in her April 10 talk. Join us by videocast live or later.

Contact Information:

Vermont Genetics Network
University of Vermont
120A Marsh Life Science Building
Burlington, VT 05405-0086
(802) 656-9119
(802) 656-2914 - FAX
vgn@uvm.edu

Contact the Webmaster:
vgnwebstaff@list.uvm.edu

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