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Pathways: The Regeneration Issue

Wed, 2019-11-13 09:27
Cover of Pathways student magazine.

NIGMS and Scholastic, Inc., are excited to bring you the next edition of Pathways, a collection of free resources that teaches students about basic science, its importance to human health, and exciting research careers.

Pathways is designed for grades 6 through 12. The topic of this unit is regenerative medicine, a field that focuses on restoring or healing damaged body parts so that they function normally. The long-term goal is to stimulate tissue and organs to heal themselves.

You’ll find information on:

  • How studying creatures that regenerate tissue may help treat human disease
  • Different jobs for researchers in a lab
  • NIGMS scientists who study regeneration and the discoveries they’re unlocking
  • How to write a research question and develop a hypothesis
Featured in This Issue:

Thomas Lozito, assistant professor at the University of Southern California

Celina Juliano, assistant professor at the University of California, Davis

Voot P. Vin, director of scientific services at MDI Biological Laboratory

Lamont R. Jones, department vice chair at Henry Ford Health System

Mansi Srivastava, assistant professor at Harvard University

Alejandro Sánchez Alvarado, scientific director at the Stowers Institute for Medical Research

Pathways [PDF, 3.23MB]  was distributed to teachers as a special insert in the October issue of Scholastic’s Science World magazine, and anyone can access and download materials for free on the Pathways website . Print copies of the first issue are available for order, and copies of this issue are soon on the way.

Let us know on social media how you’re sharing Pathways in your classroom by using the hashtag #NIGMSPathways!

Cool Images: A Colorful—and Halloween-Inspired—Collection

Thu, 2019-10-31 09:06

Transformations aren’t just for people or pets around Halloween. Scientific images also can look different than you might expect, depending on how they’re photographed. Check out these tricky-looking images and learn more about the science behind them.

Credit: Nilay Taneja, Vanderbilt University, and Dylan T. Burnette, Ph.D., Vanderbilt University School of Medicine.

Do you have a hunch about what this image is? Perhaps something to do with dry leaves? It’s a human fibroblast cell undergoing cell division, or cytokinesis, into two daughter cells. Cytokinesis is essential for the growth and development of new cells. And fibroblasts play a big role in wound healing by helping with contraction and closure.

Credit: Scott Chimileski, Ph.D., and Roberto Kolter, Ph.D., Harvard Medical School.

Any guesses for this circular image? Look closely. It’s a biofilm, a highly organized community of microorganisms that develops naturally on certain surfaces. Bacteria, fungi, and protists (one-celled eukaryotes) all can form biofilms. Many biofilms can have positive effects on people, but they also can be harmful. The dime-sized example shown here, for instance, was formed by a bacterium that can cause antibiotic-resistant infections in people. Scary stuff. This probably isn’t something you’d want to see in real life.

Credit: Dylan T. Burnette, Ph.D., Vanderbilt University School of Medicine.

Though the image shown here may look futuristic to some, its subject has a long past. This colorful shot shows a human HeLa cell dividing into two daughter cells. HeLa cells are immortal cell lines used in scientific research. They come from cervical cancer cells that were obtained in 1951 from Henrietta Lacks, a patient at the Johns Hopkins Hospital. These cells were the first that could be shared and easily multiplied in a lab setting. Although initially collected without permission, these cells have contributed to medical research and scientific breakthroughs, from the study of leukemia and cancer to the polio vaccine. In recent years, the National Institutes of Health (NIH) has worked with the Lacks family to establish a process for controlled access to data derived from HeLa cells. These cells continue to help researchers today.

Credit: Crystal D. Rogers, Ph.D., University of California, Davis, School of Veterinary Medicine, and Mariano A. Loza -Coll, Ph.D., California State University, Northridge.

If you thought this was part of a delicate brooch or some other piece of jewelry, we wouldn’t blame you. It’s really an image of a stained fruit fly ovary. And although you can’t see this specimen with the naked eye, here it’s surprisingly pretty. To capture this view, researchers stained the ovary to examine it closer. They then used this image to show molecular staining and high-resolution imaging techniques to students.

Credit: Michael Shen, Ph.D., Jasmine Temple, Leslie Mitchell, Ph.D., and Jef Boeke, Ph.D., New York University School of Medicine; and Nick Phillips, James Chuang, Ph.D., and Jiarui Wang, Johns Hopkins University.

Can you guess what this artistic image is made from? It’s yeast! Yes, that ingredient people use to bake. Researchers created this skyline of New York City by “printing” nanodroplets containing baker’s yeast onto a large plate. Yeast is a single-celled fungus, and each dot is a separate yeast colony. As the colonies grew, a picture took shape, which became “yeast art.” To make the colors (especially fitting for Halloween), the yeast strains were genetically engineered to produce pigments naturally made by bacteria, fungi, and sea creatures such as coral and sea anemones. Using genes from other organisms to make biological compounds sets the stage to someday use yeast to make other useful things, from food and fuels to drugs.

Visit the NIGMS Image and Video Gallery to peek at many more cool images.

On the RISE: Joshua and Caleb Marceau Use NIGMS Grant to Jump-Start Their Research Careers

Wed, 2019-10-23 09:02

A college degree was far from the minds of Joshua and Caleb Marceau growing up on a small farm on the Flathead Indian Reservation in rural northwestern Montana. Their world centered on powwows, tending cattle and chicken, fishing in streams, and working the 20-acre ranch their parents own. Despite their innate love of learning and science, the idea of applying to and paying for college seemed out of reach. Then, opportunities provided through NIGMS, mentors, and scholarships led them from a local tribal college to advanced degrees in biomedical science. Today, both Joshua and Caleb are Ph.D.-level scientists working to improve public health through the study of viruses.

Joshua Discovers Unexpected Opportunities

Joshua Marceau at Salish Kootenai College, where he gained research experience as an undergraduate. Credit: Joshua Marceau.

As the oldest of four brothers, Joshua was the trailblazer in the family. But like most trailblazers, his path to a scientific career wasn’t always smooth. He attended a reservation school until sixth grade, then was homeschooled. He earned his GED through the local tribal community college, Salish Kootenai College (SKC) in Pablo, so he could begin to take college-level chemistry.

When Joshua started at SKC, he was taking classes while working full time at a local waste management company hauling garbage. That changed when SKC received a Research Initiative for Scientific Enhancement (RISE) grant from NIGMS. The RISE program is designed to increase diversity in science by providing grants to institutions with a commitment to and history of developing students from populations underrepresented in biomedical sciences. The program helped SKC build a lab focused on molecular biology and biochemistry. The grant also gave support to students to work on research projects. Joshua and Caleb were the first two students at SKC to be supported as research assistants on the RISE grant.

Through the RISE program, Joshua met Mary Poss, a biology professor at the University of Montana in Missoula. Joshua and the other RISE scholars took road trips to her lab to learn basic molecular biology techniques. With guidance from SKC mentors and Poss, Joshua applied for scholarships so he could afford to quit his job and attend school full time.

Joshua followed Poss to Pennsylvania State University in University Park, where he earned his undergraduate degree in molecular biology. “I probably wouldn’t have left the reservation if I didn’t have someone to go with who I could trust,” says Joshua. “The personal mentorship needed to come first.”

He then returned home to get his Ph.D. at the University of Montana. For his dissertation, he studied vaccines for Ebola virus and hantaviruses  at the nearby National Institutes of Health (NIH) Rocky Mountain Laboratory. Now, he’s conducting postdoctoral research on HIV in the lab of Julie Overbaugh  at the Fred Hutchinson Cancer Research Center in Seattle, Washington. HIV is a major problem on the Flathead Indian Reservation where he grew up, and probably other Native American reservations  as well, he notes.

Joshua returned to SKC this summer to give students an overview of what a career in biomedical research is like. In addition, he’s working to build bridges between the Fred Hutchinson Cancer Center and SKC to give students the opportunity to experience biomedical science at top laboratories in the country.

Caleb Explores Possibilities in Biomedicine

Caleb Marceau preparing specimens at SKC. Credit: Caleb Marceau.

Joshua’s younger brother Caleb, who worked changing oil and selling auto parts, was following close behind. Like Joshua, he took advantage of the opportunities provided by the RISE grant at SKC, trading his work in the garage for full-time pursuit of a college degree.

“It was very important for me to have an older brother blazing a trail,” says Caleb. “Quitting a stable job and going to college seemed like a really risky move. I don’t know if I could have done it on my own.”

Like Joshua, Caleb knew he needed a mentor to help him navigate his academic path. Through SKC instructor Michael Ceballos, Caleb met Ken Stedman at Portland State University in Oregon. Stedman invited Caleb to work in his lab and mentored him, encouraging him to finish his undergraduate degree in microbiology and molecular biology.

Caleb received an NIH undergraduate scholarship that gave him the opportunity to spend summers doing research at NIH in Bethesda, Maryland. One summer, Caleb attended a program at Stanford University for a few days. That short visit inspired him to pursue his Ph.D. After graduating from Portland State, he returned to Montana and worked for NIH at Rocky Mountain Lab before applying to graduate school. He was accepted to both Harvard and Stanford, but followed his dream to someday return to California. Caleb studied microbiology and immunology at Stanford, working on a vaccine for the dengue fever  virus in the lab of Jan Carette .

After finishing his doctorate, Caleb landed a dream job working on dengue at the Chan Zuckerberg Biohub, a medical science research center funded by Facebook founder Mark Zuckerberg and his wife, Priscilla Chan. Now, he’s a scientist at NGM Biopharmaceuticals.

Success, Thanks to Mentors, But With Bittersweet Compromises

Although the brothers encourage young students in their tribal community to pursue careers in biomedical science, they’re also frank about some of the challenges specific to Native American scientists—some of which they didn’t even imagine when they were just starting out. For example, one challenge is that there is no thriving biomedical community near the reservation. “We always expected to go home,” says Joshua, but most jobs suited for the brothers’ training are located in big metropolitan hubs.

Whatever path the Marceau brothers ultimately choose, connecting with mentors still remains a critical part of their plan. One highlight for Joshua was that he was finally able to meet Clifton Poodry, former director of the NIGMS Division of Training, Workforce Development, and Diversity who awarded SKC that first RISE grant many years ago. “I knew that Clif, a very successful biomedical scientist, was out there, but no one encouraged me to meet him,” Joshua says. “I’m so glad that I finally got to meet him, right before he retired.”  

The brothers credit their mentors for helping them to not only obtain scholarships that provided necessary support, but also to navigate and succeed in an academic culture that was foreign to them and many miles away from their reservation.  

Interview With a Scientist: Unlocking the Secrets of Animal Regeneration With Alejandro Sánchez Alvarado

Wed, 2019-10-09 09:50

Most of what we know comes from intensive study of research organisms—mice, fruit flies, worms, zebrafish, and a few others. But according to Alejandro Sánchez Alvarado , a researcher at the Stowers Institute for Medical Research in Kansas City and a Howard Hughes Medical Institute Investigator, these research organisms represent only a tiny fraction of all animal species on the planet. Under-studied organisms could reveal important biological phenomena that simply don’t occur in the handful of models typically studied, he says.

Sánchez Alvarado’s work focuses on the planarian, a type of flatworm. Its remarkable ability to regenerate whole bodies from tiny fragments is still not fully understood. In a video interview, Sánchez Alvarado describes his discovery that cells called neoblasts are essential for regeneration. In fact, a tiny fragment of the worm can regenerate a whole body as long as the fragment contains a single neoblast. His team was able to purify neoblasts and study their gene activity, getting us closer to understanding how adult stem cells in a planarian regenerate missing body parts. These discoveries could lead to important applications in regenerative medicine.

Sánchez Alvarado also explained his research at the 2018 Dewitt Stetten Jr. Lecture.

NIGMS has supported Sánchez Alvarado’s work since 1994 under grants F32GM016775, R01GM057260, R37GM057260, and R01GM088269. He has also received support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Deafness and Other Communication Disorders.

Back to School: Top Tips for Undergraduates Eyeing Careers in Biomedical Sciences

Wed, 2019-09-11 09:37

Finding a career path in biomedical research can be challenging for many young people, especially when they have no footsteps to follow. We asked three recent college graduates who are pursuing advanced degrees in biomedical sciences to give us their best advice for undergrads.

Tip 1: Talk with mentors and peers, and explore opportunities.

One of the most challenging things for incoming undergraduates is simply to find out about biomedical research opportunities. By talking to professors and peers, students can find ways to explore and develop their interests in biomedical research.

Credit: Mariajose Franco.

Mariajose Franco, a first-generation college student, recently graduated with honors and dual degrees in molecular and cellular biology and physiology from the University of Arizona in Tucson. She’s now in a postbaccalaureate program at the National Cancer Institute and has her eye on combined M.D.-Ph.D. programs.

As an undergraduate, a course in cancer biology piqued her interest, and she reached out to her professor, Justina McEvoy, to see if she could join her lab. As a sophomore, Franco began working on rhabdomyosarcoma, a rare childhood cancer that arises from cells that normally develop into skeletal muscle. Through the NIGMS Maximizing Access to Research Careers (MARC) program, she received support to conduct two research projects during her junior and senior years. In addition to offering research opportunities, the MARC program was instrumental in providing training in scientific writing and conference poster presentations, and navigating applications, Franco says.

“Talk to people and do some research to become more informed about the opportunities that are available,” she adds. “I didn’t become involved in research until my sophomore year because I didn’t know those opportunities were available. In fact, I didn’t really know that you could get involved in research as an undergraduate.”

Tip 2: Go to conferences. Credit: Rosa Romero.

When Rosa Romero started her undergraduate studies at California State University San Marcos, the only exposure she’d had to careers in science was from watching forensic scientists on TV shows. “Since I’m a first-generation college student, I didn’t even know careers in biomedical sciences existed,” she says.

During her junior year at Cal State San Marcos, Romero joined the MARC program, which provided funding for her to attend the Annual Biomedical Research Conference for Minority Students . There, she presented a poster about her biophysical research and was approached by the associate director of molecular biophysics and biochemistry at Yale University in New Haven, Connecticut, who encouraged her to apply for a summer research program.

Cut to a few months later, and Romero was at Yale, helping to design and build a microscope. “That’s when I started to realize that I really liked instruments and biophysical techniques,” she says. That led her to a doctoral program in biochemistry at the University of Michigan Medical School, which she’s starting this fall. Romero is quick to credit MARC: “If it wasn’t for the program, I wouldn’t have discovered the thing that I really want to do.”

For undergraduates aiming for graduate school, start researching programs early, Romero advises, and try to meet with program representatives at conferences. “It’s an interesting experience trying to figure out what programs are best for you,” she says. “Looking at school websites is one thing, but visiting and meeting people can give you a whole other vibe,” she says.

Tip 3: Take your time.

Although some, like Romero, go straight to graduate school after college, sometimes it makes sense to gain additional work or research experience first.

Credit: Hunter McCurdy.

Hunter McCurdy got his start in research working in a parasitology lab at Casper Community College, through the Wyoming IDeA [Institutional Development Award] Networks of Biomedical Research Excellence program . After transferring to the University of Wyoming in 2015, McCurdy worked in another lab developing synthetic spider silk proteins. “The research really helped me in school because I was actually applying what I was learning in the classroom,” he says.

McCurdy sought work experience after graduating with a bachelor’s in physiology in 2017. He became a medical scribe in the local emergency room, where he gained some clinical experience. “You can learn about illness in a textbook, but seeing it present is totally different,” he says. “It was very enlightening.”

The experience helped McCurdy decide to go to medical school rather than graduate school. This fall, he’s heading to Yale School of Medicine. Ultimately, he’d like to work in underserved places, whether it’s internationally for Doctors Without Borders or at home in rural Wyoming.

“Take your time. You don’t want to rush into this,” McCurdy says. “I wanted to give myself the best shot possible. In my experience interviewing, they look favorably upon students who take some time to get real-life experience. That shows you are actually committed to the path that you’re on.”

NIGMS Career Development Resources

Career development is a continual process—one in which you’ll never stop growing and learning. NIGMS has resources to support biomedical scientists from the high school to faculty level. To learn more about what it’s like to work as a researcher or how to become one, check out the resources on our Being a Scientist webpage, as well as our research training and career programs.

Get Kids Excited About Science: Free STEM Resources

Wed, 2019-08-28 09:51
Credit: University of Nebraska, Lincoln.

We have a new Science Education and Partnership Award (SEPA) webpage, featuring free, easy-to-access, SEPA-funded resources that educators nationwide can use to engage their students in science. The SEPA program supports innovative STEM  and informal science education   projects for pre-kindergarten through grade 12. The program includes tools that teachers, scientists, and parents can use to excite kids about science and research, such as:

  • Apps
  • Interactivities  
  • Online books
  • Curricula and lesson plans
  • Short movies

Topics include sleep, cells, growth, microbes, healthy lifestyle, genetics, and many other subjects. By encouraging interactive partnerships between health researchers, educators, schools, and other interested organizations, the SEPA program aims to motivate students from underserved communities to consider careers in research and to improve community health literacy.

Explore the SEPA teaching resources webpage for current materials and check back to the webpage for new ones.

Advances in 3D Printing of Replacement Tissue

Wed, 2019-08-21 10:00
A bioprint of the small air sac in the lungs with red blood cells moving through a vessel network supplying oxygen to living cells. Credit: Rice University.

A team of bioengineers, funded in part by NIGMS, has devised a way to use 3D bioprinting technology to construct the small air sacs in the lungs and intricate blood vessels. When hooked up to a machine, the air sacs can “breathe,” and the blood flowing through the tiny blood vessels can take up oxygen, much like they would in an animal’s body. In the long term, this technology may allow the production of replacement organs for patients who need them. Visit the NIH Director’s Blog to read more and watch a video from Rice University’s Miller Lab .

RNA Polymerase: A Target for New Antibiotic Drugs?

Wed, 2019-08-07 10:21

DNA, with its double-helix shape, is the stuff of genes. But genes themselves are only “recipes” for protein molecules, which are molecules that do the real heavy lifting (or do much of the work) inside cells.

Artist interpretation of RNAP grasping and unwinding a DNA double helix. Credit: Wei Lin and Richard H. Ebright.

Here’s how it works. A molecular machine called RNA polymerase (RNAP) travels along DNA to find a place where a gene begins. RNAP uses a crab-claw-like structure to grasp and unwind the DNA double helix at that spot. RNAP then copies (“transcribes”) the gene into messenger RNA (mRNA), a molecule similar to DNA.

The mRNA molecule travels to one of the cell’s many protein-making factories (ribosomes), which use the mRNA message as instructions for making a specific protein.

Because making proteins is essential for life, so is RNAP. All living organisms—from humans down to bacteria—have RNAP.

Due to its vital role, RNAP also makes an excellent target for medicines. Drugs that interfere with the form of RNAP present in bacteria (but not the form of RNAP present in humans) can effectively kill bacteria while leaving the human RNAP intact, making them great candidates for treating infections. 

Richard H. Ebright , a scientist at Rutgers, The State University of New Jersey, is studying RNAP to learn how it copies information in DNA. His goal is to find new ways to kill bacteria, particularly bacteria that are resistant to current antibiotics. He asks questions such as:

  • How does RNAP find the right place to start copying the recipe for a protein?
  • How does RNAP grasp and unwind the DNA double helix to start copying the recipe?
  • How does RNAP move along DNA as it copies the recipe?
  • How do drugs that inhibit bacterial RNAP work?
  • Can we find new drugs that inhibit bacterial RNAP?

The RNAP-DNA connection is extremely fast and nearly invisible, even using sensitive equipment, so scientists are still seeking answers to many of these questions. But researchers have made a lot of progress. In particular, they now have a much better idea of how various antibiotics stop RNAP from working.

In a 2018 study, for example, Ebright and his team first described how fidaxomicin, a new antibiotic, was able to fight formidable bacteria such as Clostridium difficile. The key was its ability to stop RNAP. Fidaxomicin works by binding to RNAP at the base of one of the two pincers of the RNAP claw. This prevents the claw from grasping and unwinding DNA.

Credit: Wei Lin and Richard H. Ebright.

A year earlier, in 2017, Ebright and his team examined another antibiotic, called pseudouridimycin (PUM), which is produced by a microbe isolated from a soil sample collected in Italy. They showed that PUM kills bacteria by mimicking a chemical building block called uridine triphosphate. RNAP uses that building block to make RNA, so it’s a key component of the instructions for the final protein. PUM prevents RNAP from making RNA by taking the place of uridine triphosphate and preventing it from binding to RNAP.

In another 2017 study, Ebright and his team looked at the antibiotic rifampin. Rifampin has always been essential for the treatment of tuberculosis but, over time, tuberculosis bacteria have become increasingly resistant to this antibiotic. The scientists traced this resistance to RNAP. They found that tuberculosis RNAP has learned how to make changes to prevent rifampin from binding to it, rendering the drug less effective. However, at the same time, the researchers found potentially new types of drugs, called AAPs (Nα-aroylN-aryl-phenylalaninamides), that kill tuberculosis bacteria by binding to a different, completely separate, binding site on RNAP. Because AAPs target this new site, they are proving effective, even against rifampin-resistant tuberculosis bacteria.

Even with promising stories such as these, the battle against disease-causing bacteria is far from over, and RNAP research will be a big part of this next chapter. “Bacteria will always acquire resistance,” Ebright says. “But for large, complex protein machines such as RNA polymerase that carry out complex tasks, there are many ways to interfere with their function and, thus, many opportunities to find new drugs.”

Ebright’s research is supported in part by NIGMS under grant number R37GM041376.

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