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NIGMS Centers Build Relationships with Blackfeet Students and Collaborate on Inflammation Research

Wed, 2020-07-08 09:52
Credit: Murray Foubister. CC BY-SA 2.0 .

As part of its commitment to cultivate a diverse and inclusive scientific workforce, NIGMS continues to nurture relationships between teaching institutions and American Indian communities nationwide to ignite student interest in biomedical science and encourage research careers. This post highlights one such collaboration between NIGMS-supported centers at Montana State University (MSU) in Bozeman and the Blackfeet Nation, a tribe of nearly 18,000 members that’s one of the largest in the United States.

Neha John-Henderson, Ph.D., Montana State University. Credit: Kelly Gotham.

Neha John-Henderson, Ph.D. , an MSU assistant professor of psychology, first met Blackfeet Community College (BCC) students through Agnieszka Rynda-Apple, Ph.D., an MSU assistant professor of microbiology and immunology who already had a working relationship with the Blackfeet community. For about a year, Drs. John-Henderson and Rynda-Apple visited BCC interns and faculty supervisor Betty Henderson-Matthews monthly to help them interpret data collected for a student-developed project. While completing this project on the link between stress and health on the Blackfeet reservation, the researchers developed relationships with the students and faculty. They listened closely to the students’ stories, experiences, and career aspirations.

“They were all really excited about learning how to conduct research,” Dr. John-Henderson says. “I think that there’s a little bit of hesitance with outsiders coming in. At the beginning they were very quiet, but their confidence really grew when they realized they could do this work, and over time we have developed this trusting partnership.”

BCC and MSU decided to start new research projects every summer, and for one of the following year’s projects, some students wanted to investigate trauma and resilience. They said that even though the Blackfeet tribe experienced a lot of historical and ongoing trauma, they were resilient, which might be tied to a sense of belonging that community members felt. Based on these ideas, the students worked with Henderson-Matthews and the MSU researchers to design a study examining the relationship between childhood trauma (such as abuse and family dysfunction), markers of immune system inflammation, and a sense of community belonging.

Student researchers from Blackfeet Community College in 2018. Credit: Bill Stadwiser.

To conduct their research, the team developed and administered a questionnaire to 90 adult members of the Blackfeet Nation that measured feelings of community belonging, along with a questionnaire on childhood trauma. They also drew blood samples to test for levels of two inflammation markers. The findings suggested that a strong connection to the community may help protect individuals from the negative health impacts of childhood trauma.

Megan Gordon, who helped conduct the study while she was a student at BCC, says, “We were exposed to everything in the research world: starting a study, getting an institutional review board addendum approved, interacting with participants, testing the samples we gathered, analyzing them, and presenting our work at conferences.” She credits her experience as an undergrad research assistant with sparking her interest in science and is now pursuing a degree in medical lab science at the University of Montana. Ultimately, Gordon hopes to run her own research lab.

Jerry Racine, a student from the Blackfeet community who attended MSU, also helped conduct the study as an undergrad research assistant at BCC. He says BCC’s research opportunities enable students to combine their understanding of their community with “the resources and knowledge to address some of the problems and maybe help find ways to improve them.” He strongly believes that it’s important to show American Indian students the opportunities available to them in science. Racine currently works as an elementary school teacher and coach on the Fort Belknap Indian Reservation.

On working with students from the Blackfeet community, Dr. John-Henderson says, “I think it was so critical to develop that strong working relationship before, and once that groundwork was laid, it made it possible to answer so many research questions that would’ve been virtually impossible to do independently.” Drs. John-Henderson and Rynda-Apple continue to collaborate with students at BCC; they’re currently developing projects to investigate whether increasing levels of connectedness to Blackfeet history and traditions leads to more positive health outcomes.

This research was supported by NIGMS grants P20GM103474, P20GM104417, and U54GM115371. NIGMS-supported programs at MSU include:

Phosphorus: Glowing, Flammable, and Essential to Our Cells

Wed, 2020-07-01 10:49

Of the 118 known elements, scientists believe that 25 are essential for human biology. Four of these (hydrogen, oxygen, nitrogen, and carbon) make up a whopping 96 percent of our bodies. The other 21 elements, though needed in smaller quantities, perform fascinating and vital functions. Phosphorus is one such element. It has diverse uses outside of biology. For example, it can fuel festive Fourth of July fireworks! Inside our bodies, it’s crucial for a wide range of cell functions.

Phosphorus plays a vital role in life as part of DNA’s backbone. Red phosphorus helps ignite matches, and white phosphorus glows in the presence of oxygen. Credit: Compound Interest.
CC BY-NC-ND 4.0 . Click to enlarge

A Volatile and Versatile Discovery

Joseph Wright of Derby’s The Alchemist Discovering Phosphorus depicts Hennig Brand’s discovery of phosphorus.

Phosphorus is the first element with a recorded discovery story. Today, we extract it from phosphate rocks, but it was first isolated from human urine in 1669. In an attempt to create the philosopher’s stone (a substance, according to legend, that could turn metals into gold), German alchemist Hennig Brand boiled down a large amount of human urine into a paste. He then heated the paste until it produced a vapor that condensed into white, waxy droplets. Because the new substance glowed, he named it “phosphorus,” from the Greek word for “light-bearer.”

White phosphorus glows in the dark. Credit: Endimion17. CC-BY-SA 3.0 .

Phosphorus comes in two main forms. White phosphorus, the type that Brand collected, is poisonous, can cause severe burns, and spontaneously bursts into flame at around 86 degrees Fahrenheit if exposed to air. Its volatility makes it useful for flares, fireworks, and weaponry. Scientists later discovered the other main form of phosphorus, red phosphorus, which is stable, nontoxic, and doesn’t glow. You can find red phosphorus on the striking surface of safety match boxes.

These uses, along with applications in processes such as steel manufacturing and fine china production, make up a small percentage of the uses for phosphorus in the United States. The vast majority of U.S. phosphorus is used to produce fertilizers and supplements for livestock because phosphorus is an essential mineral for plants and animals.

The “Us” in Phosphorus

Phosphorus helps hold the DNA double helix together. Credit: NIGMS.

Like other living things, we need phosphorus in our diets, and getting enough of the mineral from our food is easy. Phosphorus deficiencies are very rare and are usually only seen when people are near starvation.

On average, our bodies contain about 750 grams of phosphorus, and about 85 percent of it is stored in our bones and teeth. But the phosphorus in our bodies isn’t found on its own. Instead, it’s found in compounds with other molecules. In addition to strengthening our bones, these compounds are important components of cell membranes and of our cells’ energy currency, adenosine triphosphate (ATP). Phosphorus-containing compounds also activate many enzymes and hormones, as well as help red blood cells deliver oxygen to different parts of our bodies.

Even our DNA needs phosphorus. DNA molecules look like twisted ladders; they have two long sides with rungs, called bases, in between. The bases carry hereditary information, and the long sides keep the bases organized. Phosphate, a compound made up of a phosphorus atom and four oxygen atoms, connects the sugars that make up the long sides, or backbones, of DNA.

Overall, for the small percentage of our bodies that phosphorus makes up, it has a huge impact on our biology. It doesn’t have the power of the philosopher’s stone that Brand was searching for when he discovered the element, but it’s even more valuable.

NIGMS Research Support

NIGMS funds a wide range of research focused on improving the molecular-level understanding of basic biological processes. These studies include exploring phosphorus’ role in such processes. Ultimately, understanding the function of elements and molecules in biological systems can help researchers develop ways to detect or treat diseases.

Exploring Nature’s Treasure Trove of Helpful Compounds

Wed, 2020-06-24 09:44
A cone snail shell. Credit: Kerry Matz, University of Utah.

Over the years, scientists have discovered many compounds in nature that have led to the development of medications. For instance, the molecular structure for aspirin came from willow tree bark, and penicillin was found in a type of mold. And uses of natural products aren’t limited to medicine cabinet staples and antibiotics. A cancer drug was originally found in the bark of the Pacific yew tree, and a medication for chronic pain relief was first isolated from cone snail venom. Today, NIGMS supports scientists in the earliest stages of investigating natural products made by plants, fungi, bacteria, and animals. The results could inform future research and bring advances to the field of medicine.

Seaweed Empowers Neuroscience Research

Red seaweed is the original source of kainic acid. Credit: Toshiaki Teruya, University of Ryukyus, Japan.

Helpful natural products have originated in a vast range of environments, from a golf course in Texas to the forests of India. One place researchers continue to explore because of its rich biodiversity is the ocean. Bradley Moore, Ph.D. , a professor of pharmacy and pharmaceutical sciences and a member of the Scripps Institution of Oceanography at the University of California, San Diego, studies how marine microbes produce antibiotics, anticancer agents, and other natural products. One of his areas of focus is developing new tools and approaches to identify genes that code for natural products and learning how these products are assembled.

Recently, Dr. Moore discovered a faster and more environmentally friendly way to synthesize kainic acid—a compound produced by some types of red seaweed—that’s valuable for neuroscience research. During a global shortage of this compound in 2000, researchers developed more than 70 chemical synthetic versions. However, the processes for making these synthetic versions have a minimum of six steps and low production rates. Plus, they’re expensive. Dr. Moore’s lab set out to identify the genes that code for the production of kainic acid in red seaweed and found that these genes enabled the seaweed to produce kainic acid in only two steps. By inserting the genes into bacteria, the researchers found they were able to produce gram quantities of kainic acid. This discovery could enable faster and more affordable manufacturing of kainic acid in the future.

Discovering New Antibiotics

Many antibiotics originate from natural compounds that some bacteria produce to protect themselves from other bacteria, and researchers grow a variety of bacteria in the lab to search for new, helpful natural products. But recent discoveries have shown that these bacteria are often capable of producing a greater variety of natural products, including potential antibiotics, than they do under laboratory conditions. In addition, for every bacterial species that grows easily in the lab, there are about a hundred that are difficult or impossible to grow there.

Antibiotic-resistant Staphylococcus aureus bacteria (yellow) and a dead human white blood cell (red).

Sean F. Brady, Ph.D. , tri-institutional professor at Rockefeller University in New York, New York, is developing methods to assess the natural products that bacteria, particularly bacteria in soil, create outside of the lab. He has found a way to extract the DNA that codes for these natural products from bacteria in soil and insert it into bacteria that grow well under lab conditions. This enables researchers to study many natural products that they couldn’t before. Dr. Brady hopes the new products discovered through this process will include some that can function as antibiotics and help address the current problem of antibiotic-resistant bacteria. His lab has already found a number of new antibiotics, including a class called malacidins, from soil bacteria using these methods. Early evidence suggests that malacidins could be effective in treating some antibiotic-resistant infections.

Advancing Natural Products Research with Better Libraries of Microbes

Researchers often look for new, useful natural products in microbial strain libraries, collections of microorganisms with the potential to generate natural products. However, the way scientists create these libraries is costly. In addition, the libraries sometimes have many similar microbes and, thus, many similar or identical natural products. A greater diversity of microbes would be helpful to researchers, giving them a larger range of natural products.

Brian T. Murphy, Ph.D. , associate professor of pharmaceutical sciences, and Laura Sanchez, Ph.D. , assistant professor of pharmaceutical sciences, both at the University of Illinois at Chicago, developed a way to decrease redundancy in microbial strain libraries and created a web-based tool to help other researchers do the same. Their new method enables them to quickly gather two types of data from microbial colonies: genus and species data, and data on the types of natural products different microbes of the same species produce. Having this data allows them to remove any redundant samples and reduces the cost and effort required to search the libraries later.

Replacing Plastic

The diversity of natural products means they can be used for more than just medications. Some bacteria can produce compounds called polyhydroxyalkanoates (PHAs) that can be used in certain medical applications as biodegradable alternatives to petroleum-based plastic. For instance, there are PHA-based stitches that dissolve harmlessly on their own and don’t require a doctor to remove them. However, producing PHAs is expensive, and this limits their development and commercialization.

Ping Li, Ph.D. , an associate professor of chemistry at Kansas State University in North Manhattan, Kansas, is researching how bacteria create PHAs in efforts to produce the compound more economically. His lab focuses on understanding and manipulating proteins and enzymes, and his team is currently investigating the roles and structures of two proteins that are crucial to PHA production and influence PHA’s molecular weight, an important variable when it’s used as a raw material. If scientists can produce PHAs more affordably, the compounds could replace petroleum-based plastic normally used in applications such as tissue engineering, drug delivery, and wound dressing, helping both patients and the environment.

Dr. Moore’s research is supported by NIGMS grant R01GM085770. Drs. Murphy and Sanchez’s research is supported by R01GM125943. Dr. Brady’s research is supported by U01GM110714 and R35GM122559. Dr. Li’s research is supported by R01GM117259.

Fish Shed Light on Fatherhood in the Animal Kingdom

Wed, 2020-06-17 09:52
A family of common marmosets. Credit: Francesco Veronesi. CC BY-SA 2.0 .

Fatherhood takes many forms across the animal kingdom. For instance, mammalian fathers are often uninvolved, with only about 10 percent helping to raise their offspring. However, that small percentage of males often makes valuable contributions to their offspring’s upbringing. For instance, cotton-top tamarin and common marmoset dads have the responsibility of carrying babies—which are typically born as sets of twins—almost constantly from birth until independence.

In other groups of animals, fathers are much more likely to share responsibilities with mothers or even act as sole caregivers. Male and female birds contribute equally to raising chicks in most cases. But in rheas and emus—both large, flightless birds—fathers incubate eggs and take care of hatchlings on their own.

And most fish don’t care for their young, but out of the species that do, between one-third and one-half rely on fathers parenting alone. Perhaps the most well-known example is the seahorse, where the male becomes pregnant, carrying his mate’s fertilized eggs in a pouch on his belly until they hatch. Alison M. Bell, Ph.D. , professor of evolution, ecology, and behavior at the University of Illinois at Urbana-Champaign, is investigating paternal care in another fish species where fathers raise offspring solo: the three-spined stickleback. Her work not only helps us understand the value of paternal care for sticklebacks, but also contributes to growing evidence across many species that fatherhood changes males on a physiological level.

A male three-spined stickleback fish. Credit: Rick Lucio.

Sticklebacks are small fish, typically little more than an inch long, that live in coastal or freshwater environments. Male sticklebacks build nests before courting females, and if their courtship succeeds, the female lays eggs in the nest. After fertilizing the eggs, the male keeps watch over them for 6 or 7 days until they hatch. He scares away predators, removes any eggs that begin to grow dangerous fungi, and spends up to half of his time fanning the eggs with his fins to circulate oxygen-rich water. After the eggs hatch, he continues to care for the young fish for about another week, keeping them close to the nest until they’re ready to venture out on their own.

“It’s really remarkable how many of the different stages of care are comparable to the kinds of changes that mammalian parents experience,” says Dr. Bell. This paternal care not only keeps offspring safe, it also affects how they act after they hatch. Sticklebacks raised without fathers show significantly higher levels of behaviors associated with anxiety, and they don’t respond correctly to threats from predators. Differences in individual parenting styles, such as the amount of time dads spend patrolling for predators or fanning, may also have an effect. In addition, early results suggest parenting styles may be heritable, passed down from fathers to sons.

Dr. Bell’s research also supports a conclusion that many other scientists are reaching by studying other animals: Fatherhood changes the brains of male animals. It does so by triggering a greater production of hormones like oxytocin, estrogen, prolactin, and vasopressin. Scientists have long known that these hormones surge during motherhood across many species. But now they’re finding that the hormones also increase in male animals when they care for eggs, when their mates are pregnant, or after their mates give birth. The heightened levels of hormones are believed to encourage bonding and nurturing behaviors in fathers. As strange as it may sound, Dr. Bell says, “Hormones involved in lactation in mammals are regulating paternal care in a fish.”

Studying stickleback fish and other animals that show paternal care helps us understand both how hormones are involved in fatherhood and how and why fathering affects offspring.

Dr. Bell’s research is supported by NIGMS grant R01GM082937.

Scientist Interview: Studying the Biochemistry of Insects with Michael Kanost

Wed, 2020-06-03 09:16

Insects vastly outnumber people on our planet. Some are pests, but many are key parts of their ecosystems, and some may even hold secrets for developing new materials that researchers could use in the medical field. Michael Kanost, Ph.D. , a professor of biochemistry and molecular biophysics at Kansas State University in Manhattan, Kansas, has been researching the biochemistry of insects for more than 30 years. His lab studies the tobacco hornworm, a mosquito that carries malaria, and the red flour beetle to better understand insect exoskeletons and immune systems.

In a video interview, Dr. Kanost explains why his lab’s research could help us control pests or even develop materials for medical applications.

Dr. Kanost’s research is supported by NIGMS grant R37GM041247.

Helium: An Abundant History and a Shortage Threatening Scientific Tools

Wed, 2020-05-27 09:29

Most of us know helium as the gas that makes balloons float, but the second element on the periodic table does much more than that. Helium pressurizes the fuel tanks in rockets, helps test space suits for leaks, and is important in producing components of electronic devices. Magnetic resonance imaging (MRI) machines that take images of our internal organs can’t function without helium. And neither can nuclear magnetic resonance (NMR) spectrometers that researchers use to determine the structures of proteins—information that’s important in the development of medications and other uses.

Helium’s many uses include helping deep sea divers breathe underwater, airbags in cars to inflate, and magnets in MRI scanners to work properly. Credit: Compound Interest.
CC BY-NC-ND 4.0 . Click to enlarge

Discovering an Elusive Element

Although it’s almost indispensable today, scientists initially wondered if helium even existed on Earth. French astronomer Pierre Janssen and English scientist Joseph Norman Lockyer first observed helium, independently, in 1868 using spectroscopes. These tools separate light into measurable wavelengths. Because every element has a unique wavelength, like a fingerprint, spectroscopes let scientists identify elements in stars. When Janssen and Lockyer used spectroscopes to look at the sun, they saw one bright yellow wavelength that didn’t match any known element.

Scientists in the 1800s used spectroscopes like this one to look at the sun.

Lockyer named the mystery element after Helios, god of the sun in Greek mythology. We now know that helium is the second most abundant element in the universe (with hydrogen being the first), and most of it is in stars, like the sun. But helium wasn’t spotted on Earth until 1882, when Italian physicist Luigi Palmieri reported seeing its wavelength while analyzing lava from Mount Vesuvius. Another 13 years passed before experiments on uranium-containing rock definitively proved that helium exists on our planet.

The biggest reason scientists struggled to find helium on Earth is that nearly all of it is deep underground, made when radioactive elements break down. Helium is so light that when released into the air, it quickly escapes to outer space. Because of this, scientists thought helium was very rare on Earth until 1905, when researchers at the University of Kansas discovered that it could be found in natural gas deposits and extracted in large amounts.

The U.S. Helium Stockpile

U.S. Navy blimps escorted convoys during World War II.

During World War II, the U.S. government used helium to lift blimps because, unlike hydrogen, it isn’t flammable. U.S. Navy blimps buoyed by helium escorted thousands of ships during the war and lowered listening devices into the water to scan for submarines.

The United States continued to value helium after World War II, and in 1960, Congress passed a law creating a national helium stockpile. Over the next 13 years, the U.S. government pumped 32 billion cubic feet of the gas into a natural rock chamber under a Texas field.

The stockpile has played a large role in maintaining the United States’ status as the world’s largest helium producer. Over the last 5 years, however, the helium in the reserve has gotten low. Due to this depletion and delays in developing other sources, the demand for helium over the last few years has exceeded the supply.

Supporting Researchers Through the Shortage

All industries that use helium are feeling the impact of the shortage, but its effect on MRI and NMR machines is especially worrisome. Both machines have large magnets that require very low temperatures to work, and they use liquid helium as a super coolant because it’s about -450 degrees Fahrenheit. Turning the machines off and allowing the magnets to warm up can permanently destroy them.

A nuclear magnetic resonance (NMR) spectrometer. Credit: Center for Eukaryotic Structural Genomics.

But due to the helium shortage, some researchers have had to take the risk of shutting down their NMR machines. Seeing this and other effects of the helium shortage, NIGMS created a supplementary grant that funds the purchase of helium recovery systems. These systems can capture 80 percent or more of helium as it evaporates, meaning that less is needed to keep machines running. Helium recovery systems also save money in the long run because they last for 30 to 40 years, and operating them costs less than buying the amount of helium they recycle.

With these recycling efforts, researchers can continue using NMR machines to create high-resolution images of proteins that help us understand their complex shapes, how they function, and how they interact. These discoveries can provide insight into diseases and assist in developing treatments, because drugs typically work by either blocking or supporting the activity of specific proteins in the body.

Not everyone uses helium to help solve scientific and medical mysteries. However, its vast range of uses makes this element an essential part of modern life and, hopefully, something we can continue to benefit from for a long time.

Reusable Disinfectant Developed from Mussel “Glue”

Wed, 2020-05-20 09:45
Mimicking mussels’ natural “glue” could have multiple benefits.

Many species have developed unique adaptations to help them thrive in their environments, and scientists in a field called biomimicry use these examples as the basis for tools to help humans. Biomimicry researchers have made a wide range of products, from climbing pads modeled after gecko feet to a faster, sharp-nosed bullet train based on the beak of the kingfisher bird. The animal kingdom also provides inspiration for biomedical products. For instance, scientists at Michigan Technological University in Houghton discovered that a natural “glue” produced by mussels has antimicrobial properties and are developing a way to put these properties to use.

Bruce Lee, Ph.D. Credit: University Marketing and Communications, Michigan Technological University.

This “glue” is a sticky amino acid that helps mussels stay attached to rocks or boats in the ocean. Bruce Lee, Ph.D. , associate professor of biomedical engineering at Michigan Tech, focuses on biomimicry, and a former doctoral student from his lab, Hao Meng, Ph.D., aimed to test how this amino acid interacts with living tissue to assess its promise as a medical adhesive. In the process, Dr. Meng discovered that when the amino acid is exposed to air, it produces hydrogen peroxide as a by-product. Drs. Lee and Meng found a synthetic compound with the same key chemical structure as the mussel-produced one and decided to develop it as a wound disinfectant.

Hao Meng, Ph.D. Credit: Lengfei Han.

Dr. Meng and an interdisciplinary team of researchers turned the synthetic compound into a microgel. Despite the “gel” in its name, the microgel is a powder. Once added to a neutral pH solution such as distilled water, the microgel starts creating hydrogen peroxide and can act as a disinfectant. It will continue to release hydrogen peroxide for up to 4 days, so if it is proven safe for human skin, it could protect a wound much longer than an application of liquid hydrogen peroxide typically used in first aid.

The research team tested the effects of the microgel on two types of bacteria and two types of viruses and found that it killed all the bacteria within 24 hours and reduced both viruses’ ability to infect the body by more than 99 percent. Also, unlike liquid hydrogen peroxide, the microgel is “rechargable” when soaked in an acidic solution. Once dry, it can be stored as a stable powder for future use.

Because liquid hydrogen peroxide is bulky and can be hazardous to transport depending on its concentration, the microgel could be useful in many situations, from space travel to camping. But first, the researchers need to test the concentration of hydrogen peroxide produced by the microgel on different cell types and fine-tune it to ensure safety and efficacy. The team also plans to test the microgel against antibiotic-resistant strains of bacteria.

Dr. Lee’s research is supported in part by NIGMS grant R15GM104846.

Scientist Interview: Exploring the Promise of RNA Switches with Christina Dawn Smolke

Wed, 2020-05-13 09:36

Whether animals are looking for food or mates, or avoiding pathogens and predators, they rely on biosensors—molecules that allow them to sense and respond to their environments. Christina Dawn Smolke, Ph.D. , a professor of bioengineering at Stanford University in California, focuses her research on creating new kinds of biosensors to receive, process, and transmit molecular information. Her lab has built RNA molecules, or switches, that can alter gene expression based on biochemical changes they detect.

In a video interview, Dr. Smolke describes the way RNA switches act like light switches, turning gene expression completely on or off, or only “dimming” it. In the future, Dr. Smolke says, her lab hopes to create RNA switches that can program stem cell differentiation in human patients and make cell therapies that treat cancer more effective, among other applications.

Dr. Smolke also discussed her research in the 2019 DeWitt Stetten, Jr. Lecture.

NIGMS has supported Dr. Smolke’s work under grants F32GM064953, R21GM074767, R01GM077347, R01GM086663, RC1GM091298, and U01GM110699, the first of which was awarded in 2002. She also has received support from the National Center for Complementary and Integrative Health and the National Cancer Institute.

The Maternal Magic of Mitochondria

Wed, 2020-05-06 09:45
Mitochondria (purple) in a rodent heart muscle cell. Credit: Thomas Deerinck, National Center for Microscopy and Imaging Research.

Mitochondria (mitochondrion in singular) are indispensable. Every cell of our bodies, apart from mature red blood cells, contains the capsule-shaped organelles that generate more than 90 percent of our energy, which is why they’re often called “the powerhouse of the cell.” They produce this energy by forming adenosine triphosphate (ATP), our cells’ most common energy source. But mitochondria also support cells in other ways. For example, they help cells maintain the correct concentration of calcium ions, which are involved in blood clotting and muscle contraction. Mitochondria are also the only structure in our cells with their own unique DNA, which with rare exceptions, is inherited only from mothers. That’s why, in honor of Mother’s Day, we’re exploring this special cellular connection to moms.

Mitochondrial DNA Basics

Most scientists believe that mitochondria have their own DNA because they originated as free-living bacteria that were engulfed by primitive eukaryotic cells but not digested about 1.5 billion years ago. Instead, the two cells benefited each other and eventually developed a relationship that would evolve into more complex life, such as plants and animals.

Mitochondrial DNA forms circles, unlike the rest of our DNA. Credit: National Human Genome Research Institute.

Mitochondria’s involvement in cellular processes requires direction from both the DNA found in our cells’ nuclei and mitochondrial DNA. Mitochondrial DNA forms a circle and contains 37 genes. This makes it tiny compared to our nuclear DNA, which contains about 20,000 genes.

Mitochondrial genes provide instructions for building proteins and RNA molecules that are essential to mitochondria’s function. Although they can multiply independently of their cell, mitochondria have been part of other cells for so long that they can’t function correctly without nuclear DNA because it contains the instructions for many proteins they need. Errors in the nuclear DNA genes for these proteins or in mitochondrial DNA can cause rare, severe disorders called mitochondrial diseases. Abnormal mitochondria have also been linked to more common diseases, including several associated with aging.

Mitochondria as a Maternal Inheritance

Unlike nuclear DNA, which is inherited from both parents, mitochondrial DNA is usually inherited only from our mothers. Both egg and sperm cells contain mitochondria with mitochondrial DNA, but after fertilization the mitochondria from the sperm are almost always destroyed. Mitochondrial DNA changes very little across generations, so scientists can use it to trace maternal lineage through hundreds of thousands of years. Some studies have looked at the mitochondrial DNA of modern-day populations to help determine the migration patterns of early humans after they left Africa.

Mitochondrial DNA can be helpful for other investigations, too, such as identifying human remains when researchers don’t have DNA from the person they’re searching for but do have access to family members’ DNA. For example, Russia’s last ruling family, the Romanovs, were executed and buried in unmarked graves during the Russian Revolution, and mitochondrial DNA played a key role in identifying their remains more than 75 years later.

NIGMS Support of Mitochondria Research

Currently, NIGMS funds many scientists who study mitochondria and their DNA. Research ranges from how these organelles synthesize proteins to how they’re altered in diseases associated with aging. These studies will increase our understanding of mitochondria and could ultimately help find treatments for some diseases.

The Science of Infectious Disease Modeling

Wed, 2020-04-29 09:56

What Is Computer Modeling and How Does It Work?

Recent news headlines are awash in references to “modeling the spread” and “flattening the curve.” You may have wondered what exactly this means and how it applies to the COVID-19 pandemic. Infectious disease modeling is part of the larger field of computer modeling. This type of research uses computers to simulate and study the behavior of complex systems using mathematics, physics, and computer science. Each model contains many variables that characterize the system being studied. Simulation is done by adjusting each of the variables, alone or in combination, to see how the changes affect the outcomes. Computer modeling is used in a wide array of applications, from weather forecasting, airplane flight simulation, and drug development to infectious disease spread and containment.

In weather forecasting, for example, models are built by feeding data such as pressure, wind, temperature, and moisture into mathematical equations to predict what may happen in the future. For any given weather projection, there are many different models created that use various mathematical equations. Sometimes the models closely align with each other while other times they disagree. In either case, they need to be interpreted by an expert to provide a reliable, though not perfect, forecast. While it would be ideal to have a single model applicable to all scenarios, we have yet to develop one. Each model is complex and has strengths and weaknesses for a given scenario based on the mathematical formulas that were used and the availability and quality of relevant data.

How Do Models Help Forecast the Spread of Infectious Diseases?

In a similar fashion, multiple models exist for forecasting the spread of infectious diseases. These models use existing data related to disease transmission, symptoms and health complications, and other factors to estimate the number of people who will become infected and, in some cases, die from the disease. This helps public health professionals predict needs for critical supplies, such as clinical staff, hospital beds, and protective equipment. Developing such models becomes more complicated when data is inaccessible, unavailable, or incomplete, particularly in the case of a completely new infectious agent such as COVID-19. The effects of interventions to lessen the impact of the disease, such as access to supportive care, stringent containment measures, timely response, restriction of mobility, and diagnostic and therapeutic resources, can also be incorporated into the models. More information about mitigation strategies can be found in the Centers for Disease Control’s Community Mitigation Guidelines to Prevent Pandemic Influenza — United States, 2017.

Multiple data sources are used in conjunction with different scenarios for spread within the community to create models, leading to projections of factors such as the path of the outbreak, disease burden, and cost. As policies are adopted and the real-life situation changes, the model can be updated over and over again, thus optimizing policies. Credit: Reprinted by permission from Springer Nature: Nature Microbiology. Modelling microbial infection to address global health challenges, Meagan C. Fitzpatrick et al., 2019. Click to enlarge

Given incomplete knowledge or a gap in historical data and information, modeling can give decision-makers some level of justification for taking certain steps to mitigate risk to the general public. It is important, however, to avoid overinterpreting models. For example, in the early stages of an outbreak with very limited data, models often predict large impacts, but the reality turns out to be less dire. This phenomenon is illustrated in the pandemic influenza model below. Rather than indicating that the model was wrong, this often means that interventions had the intended effect. Continually feeding models with updated and accurate data is essential to improving their accuracy and thus their usefulness.

The graph shows the potential effects of mitigation strategies on pandemic influenza. Click to enlarge

What Is NIGMS Doing to Support Computer Modeling Research?

NIGMS funds the research of many individual scientists who are using computer modeling to understand how infectious diseases spread and to develop improved methods for detecting and mitigating infectious disease threats. In addition, the Institute supports the Models of Infectious Disease Agent Study (MIDAS) coordinating center , based at the University of Pittsburgh’s Graduate School of Public Health. The center is tasked with facilitating and coordinating infectious disease modeling research. It provides researchers in the MIDAS Network with access to datasets, experimental models, algorithms, computer code, and model parameters. It also supports cloud-computing resources for infectious disease modeling research. In addition, the center promotes the training of the next generation of infectious disease modeling researchers and maintains communication between public health agencies and the modeling research community. The goal of all of this work is to accelerate the rate of discoveries and innovation for the detection and control of infectious diseases. The MIDAS Network currently has more than 300 members, and any infectious disease scientist, practitioner, or student can request to join the network and get access to the coordinating center’s information and resources. Many of the network members are conducting research on COVID-19 and are contributing to an extraordinary international collection of data and information regarding the outbreak. In response to the COVID-19 pandemic, the coordinating center created a central online repository  for the scientific community—a clearinghouse for sharing data and data-driven discoveries about COVID-19. The more we’re able to openly share insights, data, and resources, the better positioned we’ll be to respond to this and future disease outbreaks.

Now Watch This: PBS NewsHour Student Reporting Labs Interview with Wilbert Van Panhuis
Professor and epidemiologist Wilbert Van Panhuis, M.D., Ph.D., from the MIDAS National Center of Excellence, University of Pittsburgh, discusses how he’s collecting data on COVID-19.

Cool Images: The Hidden Beauty Inside Plants

Wed, 2020-04-15 09:23

Spring brings with it a wide array of beautiful flowers, but the interior structures of plants can be just as stunning. Using powerful microscopes, researchers can peek into the many molecular bits and pieces that make up plants. Check out these cool plant images from our Image and Video Gallery that NIGMS-funded scientists created while doing their research.

Credit: Arun Sampathkumar and Elliot Meyerowitz, California Institute of Technology.

In plants and animals, stem cells can transform into a variety of different cell types. The stem cells at the growing tip of this Arabidopsis plant will soon become flowers. Cellular and molecular biologists frequently study Arabidopsis because it grows rapidly (its entire life cycle is only 6 weeks), produces lots of seeds, and has a genome that’s easy to manipulate.

Credit: Edna, Gil, and Amit Cukierman, Fox Chase Cancer Center, Philadelphia, PA.

Those of us who get sneezy and itchy-eyed every spring or fall may have pollen grains, like those shown here, to blame. Pollen grains are the male germ cells of plants, released to fertilize the corresponding female plant parts. When they are inhaled into human nasal passages, they can trigger allergies. 

Credit: Suzana Car and Mary Lou Guerinot, Dartmouth College.

Zinc is required for the function of more than 300 enzymes, including those that help regulate gene expression, in various organisms and humans. Researchers study how plants acquire and distribute zinc, and seek ways to increase the zinc content of crops to improve human health. This image, created with synchrotron X-ray fluorescence technology, shows a heat map of zinc levels in an Arabidopsis thaliana plant leaf.

Visit our Image and Video Gallery for more fascinating images.

All About Grants: Basics 101

Wed, 2020-04-08 09:22

Note to our Biomedical Beat readers: Echoing the sentiments NIH Director Francis Collins made on his blog, NIGMS is making every effort during the COVID-19 pandemic to keep supporting the best and most powerful science. In that spirit, we’ll continue to bring you stories across a wide range of NIGMS topics. We hope these posts offer a respite from the coronavirus news when needed.

Scientific research requires many resources, which all require funding.
Credit: Michele Vaughan.

Scientific inspiration often strikes unexpectedly. The Greek mathematician and inventor Archimedes first thought of the principles of volume while taking a bath. Otto Loewi designed an important experiment on nerve cells based on a dream involving frog hearts.

But going from an initial moment of inspiration to a final answer can be a long and complex process. Scientific research requires many resources, including laboratory equipment, research organisms, and scientists’ time. And all of this requires funding. Government grants support the majority of research in the United States, and the main source of these grants for biomedical researchers is the National Institutes of Health (NIH). NIH is the primary federal agency for conducting and supporting basic, clinical, and translational medical research. It investigates the causes, treatments, and cures for both common and rare diseases.

NIGMS, one of NIH’s 27 institutes and centers, funds researchers who investigate how living systems work at a range of levels, from molecules and cells to tissues and organs, in both research organisms and humans. Understanding how living systems work is crucial for determining how they malfunction in disease, and understanding the causes of disease is essential for developing treatments. That’s why the type of research that NIGMS funds is the starting point of all modern disease prevention and treatment. NIGMS currently supports more than 3,000 researchers through more than 5,000 grants.

NIGMS offers a variety of grants that serve different purposes. The most common type of grant funds a single research project over several years. But others fund small businesses, research resources, and educational products. NIGMS also provides grants that encourage diversity and support student research. Applying for a grant is a highly competitive process, and the following steps provide an overview.

NIGMS grant recipients have made many valuable discoveries that affect people’s health every day. For example, they’ve:
  • Increased the survival rate from burn injuries by improving methods of wound care, nutrition, and infection control
  • Explained how genes affect the way a person responds to certain medications, including those to treat cancer and prevent blood clots
  • Shed light on the critical functions of carbohydrates, sugar molecules found on all living cells that are vital to fertilization, inflammation, blood clotting, and viral infection
  • Modeled infectious disease outbreaks and the impact of interventions through computer simulations to provide valuable information to public health policymakers

NIGMS continues to support thousands of researchers so that even greater discoveries can be made in the future. And since the Institute is part of the federal government, we all help support important scientific discoveries as well when we pay taxes.

In an upcoming series of posts, we’ll be exploring different types of grants and some of the research they’re funding.

Twisting and Turning: Unraveling What Causes Asymmetry

Thu, 2020-04-02 09:39

Note to our Biomedical Beat readers: Echoing the sentiments NIH Director Francis Collins made on his blog, NIGMS is making every effort during the COVID-19 pandemic to keep supporting the best and most powerful science. In that spirit, we’ll continue to bring you stories across a wide range of NIGMS topics. We hope these posts offer a respite from the coronavirus news when needed.

Asymmetry in our bodies plays an important role in how they work, affecting everything from function of internal systems to the placement and shape of organs. Take a look at your hands. They are mirror images of each other, but they’re not identical. No matter how you rotate them or flip them around, they will never be the same. This is an example of chirality, which is a particular type of asymmetry. Something is chiral if it can’t overlap on its mirror image.

Our hands are chiral: They’re mirror images but aren’t identical.

Scientists are exploring the role of chirality and other types of asymmetry in early embryonic development. Understanding this relationship during normal development is important for figuring out how it sometimes goes wrong, leading to birth defects and other medical problems.

Decoding the Causes of Chirality

Michael Ostap, Ph.D., University of Pennsylvania. Credit: Elizabeth H. Ostap.

Michael Ostap , Ph.D., a professor of physiology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, is studying how molecules interact to build cell structures that contribute to chirality in living things. His research focuses on the motors in cells, including a motor protein called myosin 1D, which plays an important role in generating chirality.

Dr. Ostap and his lab, along with Stéphane Noselli’s team  in France, examined how myosin 1D triggers chirality during the development of fruit flies. Dr. Noselli’s lab stimulated the production of myosin 1D during the early development of fruit fly organs that usually exhibit symmetry, including the epidermis (outer skin layer) and the trachea (similar to the windpipe). They found that the presence of this protein caused the cells to wind around each other in a spiral shape. The whole fly larva twisted into this spiral, and the spirals were chiral—they always turned in the same direction.

Understanding a Protein’s Push and Pull

Further examination by the Ostap lab revealed that myosin 1D induced spiraling of another protein called actin. Actin proteins form filaments required for cells to move and change shape. In this case, the researchers found that motor activity of the myosin changes the shapes of the cells, so they form tissues in a circular, counterclockwise geometry. How these molecular interactions lead to changes in cell shape, structure, and form remains a fascinating mystery, Dr. Ostap says. Unraveling these mysteries is an important step in developing better ways to treat certain diseases. 

The Ostap lab is continuing to study myosin 1D in flies with a bottom-up approach—from protein to cell to tissue. “We know that this protein is important for chirality,” Dr. Ostap explains. “We’re focused on the biophysical properties of why that’s the case. For example, we are studying myosin 1D’s biochemical and structural properties to try to learn more about how it makes these actin filaments turn.”

Dr. Ostap says studying myosin 1D’s activity in vertebrate research organisms such as mice, chickens, and zebrafish is important as well. A vertebrate’s body has many more components and more complicated interactions than a fruit fly’s body. But some of the same proteins may be important across organisms. “How similar these chiral cues are is not known yet known, and something we plan to study,” he says.

Dr. Ostap’s research is supported in part by NIGMS grant R37GM057247.

Check Out Our Pinterest Board of Virtual Learning STEM Resources

Tue, 2020-03-31 10:39

The National Institute of General Medical Sciences (NIGMS) has new resources on Pinterest! Follow NIGMS  and access engaging science education materials, including virtual learning activities, scientific images, basic science articles, and more.

Virtual Learning Center

A collection of materials for educators, students, and curious minds

Our latest Virtual Learning Resources board  provides links to lessons and activities that can help classroom teachers, home-schoolers, and parents with remote education. Our new board makes it easy to identify age-appropriate STEM materials from elementary through high school, in addition to science activities for curious minds of all ages. Our resources include apps, interactives, online books, curricula and lesson plans, and short movies.

Let us know on social media which of our resources you’re using with the hashtag #NIGMSVirtualLearning.

How Errors in Divvying Up Chromosomes Lead to Defects in Cells

Wed, 2020-03-25 09:32

Note to our Biomedical Beat readers: Echoing the sentiments NIH Director Francis Collins made on his blog, NIGMS is making every effort during the COVID-19 pandemic to keep supporting the best and most powerful science. In that spirit, we’ll continue to bring you stories across a wide range of NIGMS topics. We hope these posts offer a respite from the coronavirus news when needed.

Mitosis is fundamental among all organisms for reproduction, growth, and cell replacement. When a cell divides, it’s vital that the two new daughter cells maintain the same genes as the parent.

In one step of mitosis, chromosomes are segregated into two groups, which will go into the two new daughter cells. But if the chromosomes don’t divide properly, one daughter cell may have too many and the other too few. Having the wrong number of chromosomes, a condition called aneuploidy, can trigger cells to grow out of control.

An illustration of chromosomes being segregated equally and unequally during mitosis. Credit: Deluca Lab, Colorado State University.

How chromosome segregation errors disrupt cell division is an important area of research. Although it’s been studied for decades, new aspects are still being uncovered and much remains unknown. NIGMS-funded scientists are studying different aspects of mitosis and chromosome segregation. Understanding the details can provide vital insight into an essential biological process and may also be the key to developing better drugs for cancer and other diseases.

Decoding the Mechanics of Chromosome Segregation

Sophie Dumont, University of California, San Francisco.

Sophie Dumont, Ph.D.  of the University of California, San Francisco, originally trained in physics, but fell in love with biology during graduate school. Her background in physics continues to inform her work, which focuses largely on the mechanical forces that help cells organize themselves during mitosis.

In particular, she’s studying the mitotic spindle (the structure of microtubule filaments that pulls the chromosome pairs apart) and the kinetochore (the protein structure that attaches the chromosome to the spindle).

The mitotic spindle and kinetochores are essential to cell organization during mitosis. Credit: Judith Stoffer and NIGMS.

“We’re trying to figure out how these structures, which are made of many small parts, robustly generate and respond to the force that’s needed to move the chromosomes over large distances in the cell,” she explains.

Dr. Dumont’s lab works with human cells, but she also uses a surprising model—kidney cells from rat kangaroos, a small marsupial. Rat kangaroo cells can be helpful because they have many fewer chromosomes than human cells, which makes it easier to follow a single chromosome’s trajectory during mitosis.

“Over millions of years, evolution has found a lot of clever solutions to the challenges of proper chromosome segregation,” she says. “What’s exciting to me about my research is that not only are we making discoveries that have implications for human health, but we are gaining an understanding of how nature can build a diversity of complex structures with very simple parts.”

Recreating Important Processes in the Lab

Chip Asbury, University of Washington.

Chip Asbury, Ph.D. , a scientist at the University of Washington in Seattle, also studies the mechanics of mitosis and chromosome segregation.

“I think of the mitotic spindle as a kind of machine,” he says. “Its job is to move the chromosomes in the appropriate way, while at the same time detecting any errors that may have occurred.”

Dr. Asbury’s lab conducts experiments with the spindle and related components that have been isolated or reconstructed outside the cell. Because kinetochores are made of hundreds of proteins, isolating individual parts of them allows the lab to do experiments they couldn’t do with whole cells.

Two Trypanosoma brucei seen through a microscope. Credit: Jeffrey DeGrasse, Rockefeller University.

One experiment introduces tiny artificial cargoes to the kinetochores, enabling Dr. Asbury to recreate and observe how the microtubules form attachments. In addition, Dr. Asbury has a project focusing on mitosis in trypanosomes, a unicellular organism that causes sleeping sickness. This work is a collaboration with Bungo Akiyoshi, Ph.D. , and it may lead to new drugs for targeting these parasites.

“I’m drawn to studying these kinds of fundamental processes because not only are they fascinating, but all life depends on them,” Dr. Asbury says. “Ultimately, our ability to fight complex diseases is limited by our fundamental lack of understanding about what’s happening inside the cell. Understanding how kinetochores work will eventually enable us to develop smarter drugs.”

Linking Chromosomal Errors with Cancer

Jennifer (Jake) DeLuca, Colorado State University.

Jennifer (Jake) DeLuca, Ph.D. , a researcher at Colorado State University in Fort Collins, is looking at how errors in chromosome segregation can lead to cancer. She aims to determine whether it’s possible to develop cancer drugs that target defective segregation.

“The strength of the attachment of the microtubules at the kinetochore must be very tightly controlled,” she explains. “We know that these attachments are misregulated in cancer cells, so we’re working backwards to find out why that is the case.”

A human cell undergoing mitosis with the microtubules shown in green, chromosomes shown in blue, and kinetochores shown in red.

To study the chromosome malfunctions seen in cancer, Dr. DeLuca and her team recreate them in human cell models. They transform the cells with cancer-causing genes and then use a number of imaging techniques to watch mitosis in the cells. This allows them to get at the heart of how different proteins regulate microtubule connections in cancer cells.

One of the long-term goals of this research is to figure out how to target these proteins with drugs. “Although we are a basic research lab, not a cancer lab, our work has opened up a huge toolbox of targets to explore,” Dr. DeLuca concludes. “The integration of basic research with clinical research is critical for developing effective new therapies.”

Dr. Dumont’s research is supported by NIGMS grants DP2GM119177 and R01GM134132. Dr. Asbury’s research is supported by R01GM079373 and P01GM105537. Dr. DeLuca’s research is supported by R35GM130365.

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