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CRISPR Illustrated

Thu, 2018-11-29 16:36

You’ve probably heard news stories and other talk about CRISPR. If you’re not a scientist—well, even if you are—it can seem a bit complex. Here’s a brief recap of what it’s all about.

In 1987, scientists noticed weird, repeating sequences of DNA in bacteria. In 2002, the abbreviation CRISPR was coined to describe the genetic oddity. By 2006, it was clear that bacteria use CRISPR to defend themselves against viruses. By 2012, scientists realized that they could modify the bacterial strategy to create a gene-editing tool. Since then, CRISPR has been used in countless laboratory studies to understand basic biology and to study whether it’s possible to correct faulty genes that cause disease. Here’s an illustration of how the technique works.

How the CRISPR System Works

The CRISPR system has two components joined together: a finely tuned targeting device (a small strand of RNA programmed to look for a specific DNA sequence) and a strong cutting device (an enzyme called Cas9 that can cut through a double strand of DNA).

Once inside a cell, the CRISPR system locates the DNA it is programmed to find. The CRISPR seeking device recognizes and binds to the target DNA (circled, black).

The Cas9 enzyme cuts both strands of the DNA.

Researchers can insert into the cell new sections of DNA. The cell automatically incorporates the new DNA into the gap when it repairs the broken DNA.

CRISPR has many possible uses, including:

  • Insert a new gene so the organism produces useful medicines.
  • Help treat genetic diseases.
  • Create tailor-made organisms to study human diseases.
  • Help produce replacements for damaged or diseased tissues and organs.

Surgeon Chris McCulloh Stands Up to Disability

Thu, 2018-11-15 10:43

Credit: Chris McCulloh. Chris McCulloh

Job: 4th-year general surgical resident, Morristown Medical Center in New Jersey
Grew up in: Manhattan
When not at work, he’s: Programming, coding, thinking about artificial intelligence, and machine learning
Hobbies: Writing/producing electronic music, weightlifting

Ten years ago, Chris McCulloh planned to enter medical school and fulfill his dream of becoming a surgeon. Instead, just months before he was to start med school, he ended up a patient. A freak accident—slipping on a hardwood floor, flying backwards, and landing neck-first on the edge of a glass coffee table—left him with both legs paralyzed at age 28. Undaunted, he deferred entering medical school for a year, undergoing surgery and spending months in rehab.

McCulloh prepares for surgery while “20/20” host Elizabeth Vargas stands alongside him as part of a 2017 interview.
Credit: Morristown Medical Center.

McCulloh has since finished medical school and recently completed a 2-year pediatric surgery research fellowship at Nationwide Children’s Hospital in Columbus, Ohio. He is now two-thirds of the way through his surgical residency at the Morristown (New Jersey) Medical Center, thanks to the assistance of a specialized wheelchair that allows him to stand nearly to his 6-foot-3 height and helps him perform five to six surgeries a day.

He’s received plenty of attention for being a surgeon with a disability. Along with several print media stories, he was interviewed in 2013 for CBS’ “The Doctors,” and in 2017, ABC’s “20/20” included McCulloh in an episode on physicians with disabilities. But it’s not the wheelchair that distinguishes McCulloh, says Gail Besner, a pediatric surgeon and researcher who hired McCulloh as a postdoctoral fellow. Rather, it’s his enthusiasm, natural research skills, and exceptional surgical prowess that make him special. Besner sees no reason why he won’t reach his goal of landing a highly competitive pediatric surgical residency. “I think he’s capable of doing anything he puts his mind to,” she says.

Pursuing a Dream

After the 2008 accident that left him paralyzed, McCulloh didn’t know how he would ever be able to perform surgery. But he found encouragement from the rehab physicians he worked with at Mount Sinai Hospital in New York City, as well as from several disabled physicians he met who had managed to succeed even before the 1990 Americans with Disabilities Act. He had never been one to back down from a challenge, so he headed to Case Western Reserve School of Medicine in Cleveland, Ohio, one of the schools that had accepted him before his accident. A plastic surgeon in Hawaii who also uses a wheelchair provided guidance to McCulloh about what he would need to do to become a surgeon, including finding and funding a standing wheelchair.

At Case Western, an encounter with a neurologist who worked with children inspired McCulloh to shadow a pediatric surgeon during his surgery rotation. By the end of that month, he had found his passion: performing life-saving surgery on children. It meant overcoming immense physical challenges and competing in one of the most sought-after specialties in medicine, but it was a dream he was determined to pursue.

Testing Treatments for Necrotizing Enterocolitis (NEC)

Although squeezing in 2 years of postdoctoral research alongside a veteran pediatric surgeon isn’t a mandatory part of the road to pediatric surgery, 80 to 85 percent of those who successfully earn a surgery residency take that path.

That’s how McCulloh found his way to longtime NIGMS grantee Besner, despite having no prior research experience. After Besner hired him, she discovered that McCulloh qualified for an NIGMS disability supplement. The grant kickstarted McCulloh’s research and allowed him to attend conferences where he could network and present his award-winning findings.

Besner’s lab focuses on necrotizing enterocolitis (NEC), a disease that attacks the bowel and is a leading cause of death for premature infants. McCulloh chose to pursue findings from Besner’s lab suggesting that stem cells may protect against NEC. Using a NEC rat model, McCulloh tested whether certain types of stem cells were more effective than others. Four looked promising: mesenchymal stem cells derived from amniotic fluid and from bone marrow, and neural stem cells derived from amniotic fluid and from the neonatal gut.

However, using stem cells in premature babies raises potential problems, which include stimulating tumor growth. McCulloh examined whether he could get a similar effect using a product secreted by stem cells. He studied exosomes—messenger particles that leave the cell that created them and enter other cells. McCulloh separated exosomes from the various types of stem cells and injected them into NEC-afflicted rats. He discovered that exosomes were just as effective as stem cells against NEC. Besner’s lab also tracked their progress to see where they ended up and found exosomes in highest concentrations in damaged tissue, giving even more weight to the idea that they support healing.

“These findings support the potential for a noncell-based therapy for NEC in the future,” says Besner.

As for McCulloh, though he’s still passionate about surgery, he’s discovered a new outlet in Besner’s lab. “I find myself looking at problems I encounter clinically and thinking about how I could do a study to solve them,” he says. “My plan right now is to get through my residency and a pediatric fellowship, but then there’s a good chance I’ll start up my own lab. It feeds a need I have to find solutions to problems.”

Spark Student Interest in Science with SEPA-Funded Education Materials

Wed, 2018-10-31 12:52

NIGMS cares deeply about our future generations of scientists. That’s why we continue to fund educational tools that make science exciting for students with the hope of steering them toward career paths in science. These materials are available to educators for free through the Science Education Partnership Award (SEPA) program.

SEPA funds innovative Science, Technology, Engineering, and Mathematics (STEM ) and Informal Science Education (ISE ) projects for pre-kindergarten through grade 12. By encouraging interactive partnerships between biomedical and clinical researchers and educators, schools, and other interested organizations, SEPA provides opportunities to:

  • Motivate students from underserved communities to consider careers in basic or clinical research
  • Improve community health literacy

SEPA-Funded Resources

Here are just a few SEPA-funded resources that educators can use to peak their students’ interest in science:

Charles Darwin Synthetic Interview  (middle school through grade 9, and general public)

Credit: The Partnership in Education.

In this free interactive experience for iOS and Android devices, students learn about Charles Darwin, the naturalist, geologist, and leading contributor to the fundamental principles of evolution. Students select from a list of questions to ask a virtual Darwin and receive insight into topics that include:

  • His childhood and personal quirks
  • His adventures
  • Principles of evolution
  • Public response to his discovery

Modern-day biologists and other experts provide commentary and answer questions beyond Darwin’s 19th century knowledge. A pay version of the app includes many more questions and answers. Lesson plans and other lessons on evolution  are also included with the apps, which were developed by The Partnership in Education at Duquesne University, along with several other SEPA-funded resources.

This Is How We “Role”  (kindergarten through grade 5)

Credit: Purdue University College of Veterinary Medicine.

This Is How We “Role” is a program with the long-term goal of diversifying the veterinarian-scientist workforce. Veterinarians and veterinary students help kids learn about all the careers in this field and how they can prevent and treat health conditions that impact both people and their animals.

The program’s interactive Healthy Animals! Healthy People!  explores how doctors and scientists use their “superpowers” to prevent and treat various health challenges that people and their animals face. Students engage in fun activities that exercise their own superpowers. (This resource is free but requires users to set up an account.)

In addition, the program provides online picture books in both English and Spanish. This Is How We “Role” was created through a SEPA grant awarded to the Purdue University College of Veterinary Medicine.

Monster Heart Medic  (elementary and middle school)

Credit: The Lawrence Hall of Science, University of California, Berkeley.

Monster Heart Medic is a free app for iOS and Android devices that lets students explore the cardiovascular system and how healthy living affects it.

In this educational adventure, students must help diagnose a friendly, 3-eyed monster and assist him on his path to a healthier life. Features include:

  • Animated monster stories
  • Interactive simulators
  • Hands-on tests and arcade games
  • Discussions with health professionals

Users learn about common heart conditions, diagnostic tests, and steps people can take to get and keep their cardiovascular system healthy. This app is available in both English and Spanish.

Monster Heart Medic is part of the PlayPads project produced by the University of California, Berkeley, Lawrence Hall of Science, in partnership with the University of California, San Francisco, Benioff Children’s Hospital in Oakland.

Other SEPA-Funded Projects

Interested in more? Check out last year’s SEPA blog post for other projects. Also see the SEPA website.

Excellence in Science Mentoring Honored in Washington, D.C.

Wed, 2018-09-19 09:09

Six NIGMS grantees are among this year’s winners of the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM). The award was established by the White House in 1995. This year, it went to 27 individuals and 14 organizations.

PAESMEM recipients were honored during a 3-day event in Washington, D.C. The event featured a gala presentation ceremony and a White House tour. In addition, each winner received a $10,000 grant from the National Science Foundation, which manages PAESMEM on behalf of the White House Office of Science and Technology Policy.

The event also included the first-ever White House State-Federal STEM Education Summit. During the summit, awardees joined leaders in education and workforce development from across the nation, including U.S. territories and several Native American tribes, to discuss trends and future priorities in STEM education. The discussions will inform the development of the next Federal STEM Education 5-Year Strategic Plan, which must be updated every 5 years according to the America COMPETES Reauthorization Act of 2010.

The six NIGMS-supported PAESMEM winners are listed below. In this blog, we will highlight the work of each one, starting with Ann L. Chester and John A. Pollock.

  • Ann L. Chester, Ph.D., West Virginia University
  • John K. Haynes, Ph.D., Morehouse College
  • John A. Pollock, Ph.D., Duquesne University
  • Elba Elisa Serrano, Ph.D., New Mexico State University
  • Virginia Shepherd, Ph.D., Vanderbilt University
  • Maria da Graça H. Vicente, Ph.D., Louisiana State University
Ann L. Chester, Ph.D., West Virginia University Credit: West Virginia University.

Much of Ann Chester’s career has been devoted to encouraging students of underrepresented racial or economic status to pursue careers in the health sciences. By integrating local community issues into health and science education, she engages young people in research about real-world issues that impact them and their loved ones.

An assistant vice president for education partnerships at the West Virginia University (WVU) Health Sciences Center, Chester is also founder and director of the Health Sciences & Technology Academy (HSTA), a West Virginia mentoring program. HSTA began as a pilot program in 1994 and has been funded in part by the Science Education Partnership Award (SEPA) program since 1997. It continues to help high school students overcome social and financial challenges so they can enter college and earn STEM-based undergraduate and graduate degrees.

HSTA students. Credit: Health Sciences & Technology Academy.

Chester has organized a supportive HSTA network of teachers, community members, and higher-education faculty to mentor generations of West Virginian students. Since 1998, 99 percent of HSTA graduates have attended college, and 84 percent of college graduates continue to live and work in West Virginia, further enriching local communities and economies.

HSTA has inspired similar programs across the country, including at Clemson University, the University of Tennessee, the University of Alaska, and the University of Pittsburgh. It has been so successful that TEDx invited Chester to give a presentation about the program in April 2018.

Additionally, Chester leads the WVU Health Careers Opportunity Program (HCOP), which supports the work of HSTA at a college level. The summer program, started in 1985 for students living in communities that are medically underserved, guides students toward careers in health care. Out of the 500 or so HCOP students, 68 percent earned degrees in the health professions.

Chester’s Presidential award is one of several she has received for her work. Other honors include the West Virginia University School of Medicine’s Dean’s Award for Excellence in Service to the Community (2011), Ethel and Gerry Heebink Award for Distinguished Service to WVU (2015), WVU Mary Catherine Buswell Award for Outstanding Service for Women (2016), and Women in Science and Health Advanced Career Award (2017).

John A. Pollock, Ph.D., Duquesne University Credit: Duquesne University.

John Pollock is passionate about mentoring. Along with teaching undergraduate and graduate courses in neuroscience and biology, and conducting scientific research, he’s mentored more than 150 students. About a quarter of these students have been from racial or ethnic groups underrepresented in STEM fields. Nearly all his mentees have successfully pursued graduate degrees.

Bringing Pollock’s efforts full circle, many of his former students have gone on to help underserved communities. They are now leaders in fields that include law, science, medicine, biomedical research, and teaching.

In addition to nudging students upward in their pursuit of education and careers, Pollock reaches down to impact the lives of the youngest members of the future STEM workforce. He helps organize science summer camps for Pittsburgh children from underserved areas; creates museum, planetarium, and travelling exhibits; and volunteers weekly as a reading tutor for 4- and 5-year-olds.

Furthermore, Pollock develops media resources to educate youth in STEM education and health literacy. He is founding director of A Partnership in Neuroscience Education, which has received funding from the Science Education Partnership Award (SEPA) program since 2000. The program specializes in creating educational products that make science engaging and fun for teachers, students, and learners of all ages. These resources include videos, TV shows, video games, and award-winning apps for young people and the general public. One such app is the Darwin Synthetic Interview.

Another product that Pollock created and produced is the TV show Scientastic! The show explores science, health, and social issues through the perspective of young people, blending live-action and animation. The plot mixes fictional story arcs with interviews from real doctors and scientists in and around Pittsburgh. One SEPA-funded episode, Scientastic! Are You Sleeping? is a two-time winner of the Emmy Award and comes with an accompanying viewing guide and lesson plan.

Scene from Scientastic! Are You Sleeping? Credit: Planet Earth Television.

In addition to the Presidential award, Pollock is the recipient of the Darwin Evolution/Revolution Award, NIH (2008); Carnegie Science Award, Special Achievement in Education (2011); Duquesne University Presidential Award for Excellence in Teaching (2013); and the Bayer School of Natural and Environmental Sciences Award for Excellence in Scholarship (2017). The Apple Corporation also named Pollock an Apple Distinguished Educator in 2017.

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