Genes control the most basic functions of the cell, including what proteins to make and when. In 2003, the Human Genome Project created a draft map of our genes, and now researchers have completed a draft map of the human proteome—the set of all our proteins. The map, which includes proteins encoded by more than 17,000 genes as well as ones from regions of the genome previously thought to be non-coding, will help advance a broad range of research into human health and disease.
This rainbow-hued image shows the isolated feeding tube, or pharynx, of a tiny freshwater flatworm called a planarian, with the hairlike cilia in red and muscle fibers in green. Scientists use these wondrous worms, which have an almost infinite capacity to regrow all organs, as a simple model system for studying regeneration. A research team led by Alejandro Sánchez Alvarado of the Stowers Institute for Medical Research exploited a method known as selective chemical amputation to remove the pharynx easily and reliably. This allowed the team to conduct a large-scale genetic analysis of how stem cells in a planaria fragment realize what’s missing and then restore it. The researchers initially identified about 350 genes that were activated as a result of amputation. They then suppressed those genes one by one and observed the worms until they pinpointed one gene in particular—a master regulator called FoxA—whose absence completely blocked pharynx regeneration. Scientists believe that researching regeneration in flatworms first is a good way to gain knowledge that could one day be applied to promoting regeneration in mammals.
Roughly half the world’s population is now at risk for mosquito-borne diseases other than malaria, such as yellow fever, West Nile virus and dengue fever. These three diseases are caused by flaviviruses, a type of virus that carries its genetic material as a single strand of RNA.
Flaviviruses have found a way not only to thwart our bodies’ normal defenses, but also to harness a human enzyme—paradoxically, one normally used to destroy RNA—to enhance their disease-causing abilities. A team of scientists led by Jeffrey Kieft at the University of Colorado at Denver found that flaviviruses accomplish both feats by bending and twisting a small part of their RNA into a knot-like structure.
The scientists set out to learn more about this unusual ability. First, they determined the detailed, three-dimensional architecture of the convoluted flaviviral RNA. Then, they examined several different variations of the RNA. In doing so, they pinpointed parts that are critical for forming the knot-like shape. If researchers can find a way to prevent the RNA from completing its potentially dangerous twist, they’ll be a step closer to developing a treatment for flaviviral diseases, which affect more than 100 million people worldwide.
This work also was supported by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute.
Nerve cells (neurons) in the brain use small molecules called neuropeptides to converse with each other. Disruption of this communication can lead to problems with learning, memory and other brain functions. Through genetic studies in a model organism, the tiny worm C. elegans, a team led by Kenneth Miller of the Oklahoma Medical Research Foundation has uncovered a previously unknown mechanism that nerve cells use to package, move and release neuropeptides. The researchers found that a protein called CaM kinase II, which plays many roles in the brain, helps control this mechanism. Neuropeptides in worms lacking CaM kinase II spilled out from their packages before they reached their proper destinations. A more thorough understanding of how neurons work, provided by studies like this, may help researchers better target drugs to treat memory disorders and other neurological problems in humans.
This work also was funded by NIH’s National Institute of Mental Health.
Hannele Ruohola-Baker and a team of researchers at the University of Washington recently discovered that two proteins responsible for regulating how cells break down glucose are also essential for stem cell development. The scientists showed that the proteins HIF1 alpha and HIF2 alpha are both required to reprogram adult human cells into pluripotent stem cells, which have the ability to mature into any cell type in the body. Taking a closer look at what each protein does on its own, the researchers found that HIF1 alpha was beneficial for reprogramming throughout the process, whereas HIF2 alpha was required at early stages but was detrimental at later stages of reprogramming. Because the two proteins also play a role in transforming normal cells into cancer cells, the findings could lead to future advances in cancer research.
University of Washington News Release
Once Upon a Stem Cell Article from Inside Life Science
Learning About Cancer by Studying Stem Cells Article from Inside Life Science
Sticky Stem Cells Article from Inside Life Science
This image may look complicated, but it tells a fairly straightforward tale about basic research: Learning more about basic life processes can pave the way for medical and other advances.
In this example, researchers led by Matthew Disney of the Scripps Research Institute’s Florida campus focused on better understanding the structural underpinnings of myotonic dystrophy type 2, a relatively rare, inherited form of adult-onset muscular dystrophy. While this work is still in the preliminary stages, it may hold potential for someday treating the disorder.
Some 300,000 NIH-funded scientists are working on projects aimed at improving disease diagnosis, treatment and prevention, often through increasing understanding of basic life processes.
Read the complete Inside Life Science article.
After eating, we don’t do all the work of digestion on our own. Trillions of gut bacteria help us break food down into the simple building blocks our cells need to function. New research from an international team co-led by Eric Martens of the University of Michigan Medical School has uncovered how a strain of beneficial gut bacteria, Bacteroides ovatus, digests complex carbohydrates called xyloglucans that are found in fruits and vegetables. The researchers traced the microorganism’s digestive ability to a single piece of the genome. They also examined a publicly available set of genomic data, which included information from both humans and their resident bacteria, and found that more than 90 percent of 250 adults harbored at least one Bacteroides strain with xyloglucan-digesting capabilities. These results underscore the importance of the bacteria to human health and nutrition.
This work also was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.
University of Michigan News Release
University of Michigan Host Microbiome Initiative
Gut Reactions and Other Findings About Our Resident Microbes from Inside Life Science
Body Bacteria from Findings Magazine
Springing clocks forward by an hour this Sunday, traveling across time zones, staring at a computer screen late at night or working the third shift are just a few examples of activities that can disrupt our daily, or circadian, rhythms. These roughly 24-hour cycles influence our physiology and behavior, and they’re driven by our body’s network of tiny timekeepers. If our daily routines fall out of sync with our body clocks, sleep, metabolic and other disorders can result.
Researchers funded by the National Institutes of Health have spent decades piecing together the molecular mechanisms of our biological clocks. Now, they’re building on that basic knowledge to better understand the intricate relationship among these clocks, circadian rhythms and physiology—and ultimately, find ways to manipulate the moving parts to improve our modern-day lives.
Continue reading this new Inside Life Science article
Scientists have long known that multicellular organisms use biological molecules produced by one cell and sensed by another to transmit messages that, for instance, guide proper development of organs and tissues. But it’s been a puzzle as to how molecules dumped out into the fluid-filled spaces between cells can precisely home in on their targets.
Using living tissue from fruit flies, a team led by Thomas Kornberg of the University of California, San Francisco, has shown that typical cells in animals can talk to each other via long, thin cell extensions called cytonemes (Latin for “cell threads”) that may span the length of 50 or 100 cells. The point of contact between a cytoneme and its target cell acts as a communications bridge between the two cells.
Until now, only nerve cells (neurons) were known to communicate this way. “This is an exciting finding,” says NIGMS’ Tanya Hoodbhoy. “Neurons are not the only ‘reach out and touch someone’ cells.”
This work also was funded by NIH’s National Heart, Lung, and Blood Institute.
Jasmine Johnson and Gabe Vela might still be teenagers, but they are also seasoned scientists. It all started 3 years ago, when, as high school juniors, they took the research course Independent Studies in Computational Biology at The Jackson Laboratory in Bar Harbor, Maine. They were hooked. They continued to do research until they graduated, working part-time for 2 academic years and full-time for 2 summers.
They worked with statistical geneticist Gary Churchill, using computational biology to explore the relationship between sleep and obesity. They focused on finding genes that regulate sleep and understanding how sleep affects the body. One goal of the research is to tease out a genetic explanation for why sleep deprivation increases the risk of obesity.
Working in a lab “completely changed what I thought I was going to do with my life,” said Vela. “Now I’m going to focus more on research than anything else.”
For Johnson, the experience provided the opportunity to present her research at the 2013 White House Science Fair, where she hobnobbed with some political hot shots.
“It was an amazing experience,” she said. Having “important White House officials be interested in my project … inspired me.”
Johnson and Vela visited NIH a few months ago and talked with us about their research experiences, their lives and their future goals. Jasmine Johnson & Gabriel Vela on their experience as high school researchers at The Jackson Laboratory in Bar Harbor, Maine.
Article about Johnson and Vela and other young researchers, from The Jackson Laboratory’s magazine The Search.
Article about the work of Gary Churchill, from NIH’s Findings magazine.