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LabTV: Curious about Computer Modeling of Proteins

Posted on by Dr. Francis Collins

Josh Carter

In many ways, Josh Carter is a typical college student, with a hectic schedule packed with classes and social activities. But when he enters a structural biology lab at Montana State University in Bozeman, Carter encounters an even faster paced world in which molecular interactions can be measured in femtoseconds—that is, 1 millionth of 1 billionth of 1 second.

Working under the expert eye of principal investigator Blake Wiedenheft, Carter is applying his computational skills to X-ray crystallography data to model the structures of various proteins, as well as to chart their evolution over time and map their highly dynamic interactions with other proteins and molecules. This basic science work is part of this NIH-funded lab’s larger mission to understand how bacteria defend themselves from the viruses that try to infect them. It’s a fascinating area of science with a wide range of potential applications, from treating diseases that arise from imbalances in the microbiome (the communities of microbes that live in and on our bodies) to developing new methods for gene editing and programmable control of gene expression.


LabTV: Curious About Heart Failure in Young Children

Posted on by Dr. Francis Collins

Josh Maxwell

Growing up in Pittsburgh, Josh Maxwell enjoyed romping around outdoors. He was an adventurous kid who liked to catch live frogs and snakes, lug them home, and surprise his parents with the latest creepy find. Maxwell rode his curiosity for nature to a bachelor’s degree in biology from Allegheny College, Meadville, PA. He then went on to earn a Ph.D. in cell and molecular physiology from Loyola University Chicago Stritch School of Medicine.

Maxwell, the focus of our latest LabTV video, is now a research scientist in the lab of Michael Davis at Emory University, Atlanta, where he studies pediatric heart failure. Maxwell grows cardiac cells in tissue culture and tries to fix the defects that lie within. What’s driving this important research is that a heart transplant remains the only option to save the lives of many kids born with severe congenital heart problems. In addition to shortages of donated organs, undergoing such a major operation at such a tender age can take a real toll on the children and their families. Maxwell wants to be a part of discovering non-surgical alternatives to regenerate cardiac tissue and one day repair a damaged heart for a lifetime.


LabTV: Curious About Drug Resistance of Hepatitis C Virus

Posted on by Dr. Francis Collins

Ashley Matthew

As long as she can remember, Ashley Matthew wanted to be a medical doctor. She took every opportunity to pursue her dream, including shadowing physicians to learn more about what a career in health care is really like. But, as Matthew explains in today’s LabTV video, she also became attracted to the idea of doing research because of her affinity for solving problems and “figuring things out.”

So, Matthew decided to give biomedical research a try, landing a spot in an undergraduate summer program sponsored by the University of Massachusetts. Ten weeks later, she was convinced that her future in medicine just had to include a research component. That’s why Matthew is now well on her way as an M.D./Ph.D. student at the University of Massachusetts Medical School, Worcester, where she works in the lab of Celia Schiffer.


LabTV: Curious about Pancreatic Cancer

Posted on by Dr. Francis Collins

Lindsey Briton

Growing up in Blacksburg, VA, Lindsey Brinton was constantly asking her parents how everything worked. She took this expansive natural curiosity with her to the University of Virginia, where she earned undergraduate degrees in French literature and biomedical engineering. Now a Ph.D. candidate at UVA in the lab of Kimberly Kelly—and the subject of our latest LabTV video—Brinton is posing interesting questions about pancreatic cancer.

Pancreatic cancer is one of the most difficult cancers to treat, in part, because it often spreads early and is diagnosed too late. Brinton’s research is focused on the cells that surround the tumor, the so-called stroma, and on the risk of metastasis. She wonders whether these cells display unique targets on their surface that, once discovered, can be exploited to kill the tumor cells. It’s certainly challenging research. Failures far outnumber successes. But as Brinton points out, endurance, perseverance, and keeping your eye on the big picture can lead to success.


LabTV: Curious About Fatigue Related to Cancer Therapy

Posted on by Dr. Francis Collins

Leorey Saligan

As this LabTV profile of an outstanding nurse-scientist shows, there are many different paths to a career in biomedical research. Leorey Saligan grew up in the Philippines, where the challenges and rewards of caring for sick family members inspired him to become a nurse. His first job was at a nursing home in Midland, TX, and the next at a nearby hospital. Later, Saligan moved to Norfolk, VA, where as a nurse practitioner he began caring for people with sarcoidosis, an inflammatory disease that affects several organ systems.

Saligan went on to pursue a Ph.D. in nursing at Virginia’s Hampton University, writing his dissertation on the chronic vision problems associated with sarcoidosis. To gather more data on such problems, he joined NIH’s National Institute of Nursing Research in Bethesda, MD, and, with the help of colleagues, carried out a clinical study. To Saligan’s surprise, the data showed that fatigue, rather than poor vision, was the top concern of people with sarcoidosis. That discovery sparked his research interest in fatigue—an interest now focused on the intense, often debilitating fatigue that many people with cancer experience both during and after treatment, particularly radiation therapy.

Like people with sarcoidosis, people undergoing cancer treatment report that fatigue is the symptom that most negatively affects their quality of life. Many find the fatigue so distressing that their treatment regimens have to be reduced or even halted—actions that may have a negative effect on the cancer-killing power of such treatments. And, for some folks, the fatigue can be long lasting, persisting for months or even years after cancer therapy ends.

By analyzing blood and tissue samples donated by volunteers who are undergoing or who have undergone cancer treatments, Saligan and colleagues from NIH’s Clinical Center and National Cancer Institute have uncovered several promising leads in their effort to gain a better understanding of the molecular mechanisms of treatment-related fatigue. He is also working with behavioral researchers to explore the relationship of fatigue with pain, depression, anxiety, sleep disturbances, and other symptoms. Ultimately, this NIH tenure-track investigator (who also happens to be an officer in the U.S. Public Health Service) wants to see this scientific knowledge translated into effective ways of treating or preventing the fatigue that is a most unfortunate side effect of potentially life-saving cancer therapies.

Links:

LabTV

Leorey N. Saligan (National Institute of Nursing Research/NIH)

Investigating Molecular-Genetic Correlates of Fatigue Experienced by Cancer Patients Receiving Treatment (ClinicalTrials.gov/NIH)

Effect of Ketamine on Fatigue Following Cancer Therapy (ClinicalTrials.gov/NIH)

Science Careers (National Institute of General Medical Sciences/NIH)

Careers Blog (Office of Intramural Training/NIH)

Scientific Careers at NIH

 


LabTV: Curious About a Mother’s Bond

Posted on by Dr. Francis Collins

Bianca JonesThe bond between a mother and her child is obviously very special. That’s true not only in humans, but in mice and other animals that feed and care for their young. But what exactly goes on in the brain of a mother when she hears her baby crying? That’s one of the fascinating questions being explored by Bianca Jones Marlin, the young neuroscience researcher featured in this LabTV video.

Currently a postdoctoral fellow at New York University School of Medicine, Marlin is particularly interested in the influence of a hormone called oxytocin, popularly referred to as the “love hormone,” on maternal behaviors. While working on her Ph.D.in the lab of Robert Froemke, Marlin tested the behavior and underlying brain responses of female mice—both mothers and non-mothers—upon hearing distress cries of young mice, which are called pups. She also examined how those interactions changed with the addition of oxytocin.

I’m pleased to report that the results of the NIH-funded work Marlin describes in her video appeared recently in the highly competitive journal Nature [1]. And what she found might strike a chord with all the mothers out there. Her studies show that oxytocin makes key portions of the mouse brain more sensitive to the cries of the pups, almost as if someone turned up the volume.

In fact, when Marlin and her colleagues delivered oxytocin to the brains (specifically, the left auditory cortexes) of mice with no pups of their own, they responded like mothers themselves! Those childless mice quickly learned to perk up and fetch pups in distress, returning them to the safety of their nests.

Marlin says her interest in neuroscience arose from her experiences growing up in a foster family. She witnessed some of her foster brothers and sisters struggling with school and learning. As an undergraduate at Saint John’s University in Queens, NY, she earned a dual bachelor’s degree in Biology and Adolescent Education before getting her license to teach 6th through 12th grade Biology. But Marlin soon decided she could have a greater impact by studying how the brain works and gaining a better understanding of the biological mechanisms involved in learning, whether in the classroom or through life experiences, such as motherhood.

Marlin welcomes the opportunity that the lab gives her to “be an explorer”—to ask deep, even ethereal, questions and devise experiments aimed at answering them. “That’s the beauty of science and research,” she says. “To be able to do that the rest of my life? I’d be very happy.”

References:

[1] Oxytocin enables maternal behaviour by balancing cortical inhibition. Marlin BJ, Mitre M, D’amour JA, Chao MV, Froemke RC. Nature. 2015 Apr 23;520(7548):499-504.

Links:

LabTV

Froemke Lab (NYU Langone)

Science Careers (National Institute of General Medical Sciences/NIH)

Careers Blog (Office of Intramural Training/NIH)

Scientific Careers at NIH

 


LabTV: Curious About Parkinson’s Disease

Posted on by Dr. Francis Collins

Kinsley Belle

When the young scientist featured in this LabTV video first learned about induced pluripotent stem (iPS) cells a few years ago as an undergrad, he thought it would be cool if he could someday work with this innovative technology. Today, as a graduate student, Kinsley Belle is part of a research team that’s using iPS cells on a routine basis to gain a deeper understanding of Parkinson’s disease.

Derived from genetically reprogrammed skin cells or white blood cells, iPS cells have the potential to develop into many different types of cells, providing scientists with a powerful tool to model a wide variety of diseases in laboratory dishes.  At the University of Miami’s John P. Hussman Institute for Human Genomics, Belle and his colleagues are taking advantage of an iPS model of Parkinson’s disease to explore its molecular roots. Their goal? To use that information to develop better treatments or maybe even a cure for the neurodegenerative disorder that affects at least a half-million Americans.


LabTV: Curious About Bacteria

Posted on by Dr. Francis Collins

Robert Morton IIIOther than wondering what might be lurking in those leftovers stashed in the back of the fridge, you probably don’t think much about bacteria. But Robert Morton III—a Ph.D. candidate at Indiana University, Bloomington, and the focus of our latest LabTV profile—sure does. He’s fascinated by the complicated and even beautiful ways in which bacteria interact with their environments. In fact, scientists can learn a whole lot about biology by studying bacteria and other single-celled organisms.

Working in the NIH-funded lab of Yves Brun, Morton has spent many of his days peering through microscopes into the otherwise invisible world of bacteria. His sights are set on the relatively simple, two-component interactions that enable bacteria to sense and respond to various external factors. Each of these interactions features a histidine kinase sensor partnered with a response regulator. Specifically, Morton has focused much of his research on one particular protein thought to play a role in these interactions—a protein that he calls an “orphan” because no scientist has yet identified its partner or determined quite what it does.


LabTV: Curious About Tuberculosis

Posted on by Dr. Francis Collins

LabTV-Bree AldridgeOne reason that I decided to share these LabTV profiles is that they put a human face on the amazingly wide range of NIH-supported research being undertaken every day in labs across the country. So far, we’ve met young scientists pursuing basic, translational, and clinical research related to the immune system, cancer, Alzheimer’s disease, and the brain’s natural aging process. Today, we head to Boston to visit a researcher who has set her sights on a major infectious disease challenge: tuberculosis, or TB.

Bree Aldridge, PhD, an assistant professor at Tufts University School of Medicine in Boston, runs a lab that’s combining microbiology and bioengineering in an effort to streamline treatment for TB, which leads to more than 2 million deaths worldwide every year [1]. Right now, people infected with Mycobacterium tuberculosis—the microbe that causes TB—must take a combination of drugs for anywhere from six to nine months. When I was exposed to TB as a medical resident, I had to take a drug for a whole year. These lengthy regimens raise the risk that people will stop taking the drugs prematurely or that an opportunistic strain of M. tuberculosis will grow resistant to the therapy. By gaining a better basic understanding of both M. tuberculosis and the cells it infects, Aldridge and her colleagues hope to design therapies that will fight TB with greater speed and efficiency.


LabTV: Young Scientist on a Mission to Cure Alzheimer’s Disease

Posted on by Dr. Francis Collins

Melissa Young LabTV

Time for another LabTV video! Today, I’d like you to meet Melissa Young, a third-year graduate student in the College of Pharmacy, University of Georgia, Athens. Young, who is doing research in the lab of James Franklin, says her scientific goal is to help build the scientific case that oxidative stress plays a key role in Alzheimer’s disease.

Young also has a personal reason for wanting to her research to succeed. From her experiences with a beloved grandmother and aunt, she has seen first-hand the heartbreaking effects of Alzheimer’s disease and other forms of dementia on both patients and their loved ones. Currently, there is no cure for Alzheimer’s disease and no treatments to halt or reverse its progression. That’s one of the reasons why Young has chosen to go into an area of science focused on translating basic discoveries into new therapeutics.


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