Amazing Organisms and the Lessons They Can Teach Us

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

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

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PREP Scholar’s Passion for Understanding Body’s Defenses

Photo of Charmaine Nganje, with curly red shoulder-length hair and eyeglasses, smiling..

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

Charmaine N. Nganje

Hometown: Montgomery Village, Maryland

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

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

Languages: English (and a bit of Patois)

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

Hobbies: Off-peak traveling

Q. Which NIGMS program are you involved with?

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

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Five Fabulous Fats

Happy Fat Tuesday!

On this day, celebrated in many countries with lavish parties and high-fat foods, we’re recognizing the importance of fats in the body.

You’ve probably heard about different types of fat, such as saturated, trans, monounsaturated, omega-3, and omega-6. But fats aren’t just ingredients in food. Along with similar molecules, they fall under the broad term lipids and serve critical roles in the body. Lipids protect your vital organs. They help cells communicate. They launch chemical reactions needed for growth, immune function, and reproduction. They serve as the building blocks of your sex hormones (estrogen and testosterone).

Here we feature five of the hundreds of lipids that are essential to health.

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Our Complicated Relationship With Viruses

Illustration of Influenza Virus H1N1. Swine Flu.
Nearly 10 percent of the human genome is derived from the genes of viruses. Credit: Stock image.

When viruses infect us, they can embed small chunks of their genetic material in our DNA. Although infrequent, the incorporation of this material into the human genome has been occurring for millions of years. As a result of this ongoing process, viral genetic material comprises nearly 10 percent of the modern human genome. Over time, the vast majority of viral invaders populating our genome have mutated to the point that they no longer lead to active infections. But they are not entirely dormant.

Sometimes, these stowaway sequences of viral genes, called “endogenous retroviruses” (ERVs), can contribute to the onset of diseases such as cancer. They can also make their hosts susceptible to infections from other viruses. However, scientists have identified numerous cases of viral hitchhikers bestowing crucial benefits to their human hosts—from protection against disease to shaping important aspects of human evolution, such as the ability to digest starch.

Protecting Against Disease

Geneticists Cedric Feschotte Exit icon, Edward Chuong Exit icon and Nels Elde Exit icon at the University of Utah have discovered that ERVs lodged in the human genome can jump start the immune system.

For a virus to successfully make copies of itself inside a host cell, it needs molecular tools similar to the ones its host normally uses to translate genes into proteins. As a result, viruses have tools meticulously shaped by evolution to commandeer the protein-producing machinery of human cells. Continue reading “Our Complicated Relationship With Viruses”

Nature’s Medicine Cabinet

More than 70 percent of new drugs approved within the past 30 years originated from trees, sea creatures and other organisms that produce substances they need to survive. Since ancient times, people have been searching the Earth for natural products to use—from poison dart frog venom for hunting to herbs for healing wounds. Today, scientists are modifying them in the laboratory for our medicinal use. Here’s a peek at some of the products in nature’s medicine cabinet.

Vampire bat

A protein called draculin found in the saliva of vampire bats is in the last phases of clinical testing as a clot-buster for stroke patients. Vampire bats are able to drink blood from their victims because draculin keeps blood from clotting. The first phases of clinical trials have shown that the protein’s anti-coagulative properties could give doctors more time to treat stroke patients and lower the risk of bleeding in the brain.

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Digging Deeply Into Data for the Causes of Disease

Hunting for the cause of a disease can be like tracing a river back to its many sources. Myriad factors, large and small, may contribute to a condition. One approach to the search focuses on the massive amounts of genomic and other biological data that scientists are gathering in the course of their studies. To examine this data and look for meaningful patterns and other clues, scientists turn to bioinformatics, a field focused on the development of analytical methods and software tools.

Here are a few examples of how National Institutes of Health-funded scientists are using bioinformatics to dig deeply into data and learn more about the development of diseases, including Huntington’s, preeclampsia and asthma.

Huntington’s Disease

Network of proteins that interact with huntingtin

Researchers have mapped a network of 2,141 proteins that all interact either directly or through one other protein with huntingtin (red), the protein associated with Huntington’s disease. Credit: Cendrine Tourette, Buck Institute for Research on Aging, J Biol Chem 2014 Mar 7;289(10):6709-26 Exit icon.

The cause of Huntington’s disease, a degenerative neurological disorder with no known cure, may appear simple. It begins with a change in a single gene that alters the shape and functioning of the huntingtin protein. But this protein, whether in its normal or altered form, does not act alone. It interacts with other proteins, which in turn interact with others.

A research team led by Robert Hughes of the Buck Institute for Research on Aging set out to understand how this ripple effect contributes to the breakdown in normal cellular function associated with Huntington’s disease. The scientists used experimental and computational approaches to map a network of 2,141 proteins that interact with the huntingtin protein either directly or through one other protein. They found that many of these proteins were involved in cell movement and intercellular communication. Understanding how the huntingtin protein leads to mistakes in these cellular processes could help scientists pursue new approaches to developing treatments. Continue reading “Digging Deeply Into Data for the Causes of Disease”

Correcting a Cellular Routing Error Could Treat Rare Kidney Disease

AGT protein and peroxisomes in untreated and treated cells.
The altered AGT protein (red) and peroxisomes (green) appear in different places in untreated cells (top), but they appear together (shown in yellow) in cells treated with DECA (bottom). Credit: Carla Koehler/Reproduced with permission from Proceedings of the National Academy of Sciences USA. View larger image.

Our cells have organized systems to route newly created proteins to the places where they’re needed to do their jobs. For some people born with a rare and potentially fatal genetic kidney disorder called PH1, a genetically altered form of a particular protein mistakenly ends up in mitochondria instead of in another organelle, the peroxisome. This cellular routing error of the AGT protein results in the harmful buildup of oxalate, which leads to kidney failure and other problems at an early age.

In new work led by UCLA biochemist Carla Koehler Exit icon, researchers used a robotic screening system to identify a compound that interferes with the delivery of proteins to mitochondria. Koehler’s team Exit icon showed that adding a small amount of the compound, known as DECA, to cells grown in the laboratory prevented the altered form of the AGT protein from going to the mitochondria and sent it to the peroxisome. The compound also reduced oxalate levels in a cell model of PH1.

The team’s findings suggest that DECA, which is already approved by the Food and Drug Administration for treating certain bacterial infections, could be a promising candidate for treating children affected by PH1. And, Koehler notes, the screening strategy that she and her team used to identify DECA as a potential therapy may help researchers identify other new therapies for the disorder.

This work was funded in part by NIH under grant R01GM061721.

Mighty Mitochondria

Mitochondria from the heart muscle cell of a rat.
Mitochondria (red) from the heart muscle cell of a rat. Nearly all our cells have these structures. Credit: Thomas Deerinck, National Center for Microscopy and Imaging Research Exit icon.

Meet mitochondria: cellular compartments, or organelles, that are best known as the powerhouses that convert energy from the food we eat into energy that runs a range of biological processes.

As you can see in this close-up of mitochondria from a rat’s heart muscle cell, the organelles have an inner membrane that folds in many places (and that appears here as striations). This folding vastly increases the surface area for energy production. Nearly all our cells have mitochondria, but cells with higher energy demands have more. For instance, a skin cell has just a few hundred, while the cell pictured here has about 5,000.

Scientists are discovering there’s more to mitochondria than meets the eye, especially when it comes to understanding and treating disease.

Read more about mitochondria in this Inside Life Science article.

Restoring the Function of an Immune Receptor Involved in Crohn’s Disease

Gut bacteria
Receptor proteins bind to bacterial cell wall fragments, initiating an immune response to remove bad gut bacteria. Credit: S. Melanie Lee, Caltech; Zbigniew Mikulski and Klaus Ley, La Jolla Institute for Allergy and Immunology.

Our bodies depend on a set of immune receptors to remove harmful bacteria and control the growth of helpful bacteria in our guts. Genetic changes that alter the function of the receptors can have an adverse effect and result in chronic inflammatory diseases like Crohn’s disease. Catherine Leimkuhler Grimes and Vishnu Mohanan of the University of Delaware researched a Crohn’s-associated immune receptor, NOD2, to figure out how it can lose the ability to respond properly to bacteria. In the process, they identified the involvement of a protective protein called HSP70. Increasing HSP70 levels in kidney, colon and white blood cells appeared to restore NOD2 function. This work represents a first step toward developing drugs to treat Crohn’s disease.

This work was funded in part by an Institutional Development Award (IDeA) Network of Biomedical Research Excellence (INBRE) grant.