NIGMS Biomedical Beat

Cool Image: Bacterial Glue

Thu, 19 Jan 2012 14:00:00 EST

The tiny water bacterium Caulobacter crescentus secretes a sugary substance so sticky that just a tiny bit could hold several cars together. First, it attaches to a surface at the end of its cell body, which has a propeller-like flagellum. On contact, the flagellum stops moving with help from nearby cable-like structures called pili. This arrest stimulates production of the sugary adhesive, which then is released at the attachment site and immediately binds the cell to the surface. Since binding helps some bacteria form slimy residues and hard-to-treat infections, knowing how this occurs could help us better understand how to treat and prevent such outcomes.

HIV’s Pathogenic Landscape

Thu, 19 Jan 2012 14:00:00 EST

While HIV has only a handful of proteins of its own, a new study shows that the virus makes the most of its small repertoire. Researchers used a comprehensive approach to uncover nearly 500 interactions between HIV and human proteins. The study has produced one of the most detailed surveys to date of how HIV interacts with human cells. Most of these interactions were previously unknown, opening up a vast new territory of potential drug targets for treating people infected with HIV.

Malodorous Molecule an Accessory in Cellular Suicide

Thu, 19 Jan 2012 14:00:00 EST

A factory’s assembly line goes haywire, and products in various stages of completion spill out until the line shuts down. When cells, most of which are constantly making proteins, face this challenge, they have two choices: slow down production or, if the situation is bad enough, commit suicide. Cells decide using a tightly controlled process that involves the nasty-smelling molecule hydrogen sulfide (H₂S). Better known as an explosive, highly toxic gas that reeks like rotten eggs, H₂S might help researchers understand diseases linked to excess cellular suicide like Alzheimer’s and Parkinson’s.

Riboswitch Prevents Fluoride from Fighting Bacteria

Thu, 19 Jan 2012 14:00:00 EST

The fluoride in toothpaste and tap water helps protect teeth from cavity-causing bacteria. Scientists recently learned about the events that happen when bacteria come into contact with fluoride. By mixing bacterial RNA with a variety of chemicals in a test tube, scientists discovered a group of riboswitches (sections of RNA) in bacteria that bind to fluoride. When this occurs, the fluoride-sensing riboswitch activates genes coding for ion channels that pump fluoride back out of the cell. The finding may help scientists increase the potency of fluoride and make it more toxic to bacteria.

mRNA: Marked for Destruction

Thu, 19 Jan 2012 14:00:00 EST

Many of the proteins that control cell division appear for a single step of the process and then vanish until the next round of division. A team of researchers working in yeast has now discovered how certain transient proteins are marked for destruction. As soon as they’re made, the messenger RNA molecules that serve as the proteins’ blueprints get tagged with a special protein. These tagged mRNAs later degrade in response to a cellular signal, triggering the disappearance of the proteins they encode. This work offers new insights into how cells control division and may lead to new ways to combat the runaway cell division that characterizes cancer.

Cool Image: Bet-Hedging Bacteria

Thu, 15 Dec 2011 14:00:00 EST

This time of year, to many people, blinking lights and stress mean the holidays are upon us. But to scientists at Caltech, they reveal a new understanding of how bacteria respond—at the genetic level—to a certain type of stress. To track this response, scientists studied the sigma B protein in bacterial cells. When triggered by extreme temperature, starvation or other stressors, sigma B can activate more than 150 genes. The researchers inserted a fluorescent sensor into bacterial cells so that the cells would glow green when sigma B sprang into action. Then they doused the bacteria with a chemical stressor that essentially saps the cells’ energy. As expected, sigma B flipped on. But then, just as quickly, it flipped off, even though the chemical remained in the environment. This on-off behavior, which appeared as a blinking green light, reveals that bacteria may “hedge their bets” when exposed to energy stress. Rather than dedicating all their resources for an extended period, the cells offer a brief, dramatic response, then return to their normal state, ready for a different environmental stressor. This could help bacterial populations survive in changing conditions. Because sigma B controls the disease-causing abilities of some bacteria, this research could help us better understand the genetics—and potential weaknesses—of organisms that cause a host of potentially deadly infections.

Growing Without Cell Division

Thu, 15 Dec 2011 14:00:00 EST

While some cells divide into copies to increase their numbers, others double their genetic material to increase their actual size. To better understand this process called endocycling, researchers studied fruit fly salivary gland cells, which endocycle about 10 times during the fly’s lifetime and increase in size by more than 1,000-fold. The scientists identified how specific proteins function as a molecular oscillator to drive the process. Since endocycling occurs in most plants and invertebrate animals, the findings could lead to improved agricultural methods. They also are relevant to human diseases that involve cells that endocycle, such as placental, heart, blood and liver cells.

New Therapeutic Target for Aggressive Lymphoma

Thu, 15 Dec 2011 14:00:00 EST

Diffuse Large B-cell Lymphoma is the most common type of lymphoma in adults. It has been linked to an overabundance of BCL6—a protein that binds DNA and regulates gene activities, including genes that control B-cell differentiation. Researchers have now uncovered one reason for the excess. A protein called FBXO11 normally helps keep BCL6 levels low by targeting it for degradation. But when the FBXO11 gene is mutated or deleted, BCL6 levels rise and cells can turn malignant. The discovery of FBXO11’s role offers a promising new therapeutic target for treating the disease.

Faster, Less Expensive Way to Make Heparin

Thu, 15 Dec 2011 14:00:00 EST

For more than 70 years, doctors have relied on a class of drugs called heparins to decrease the risk of blood clots in their patients. But heparins, which are made of carbohydrate subunits, are tricky to manufacture. Synthesis of one version of the drug requires 50 steps and generates large quantities of hazardous waste. A new method that uses a combination of chemical and enzymatic processes enables drug production in just 10 or 12 steps. This more efficient approach is expected to significantly reduce the cost of the medicine and may even be adapted to the synthesis of other drugs.

Hydrogen Peroxide Channel Sheds Light on Wound Healing, Tumors

Thu, 15 Dec 2011 14:00:00 EST

In response to a cut or other wound, the human body produces its own hydrogen peroxide to ward off infection and start the healing process. Scientists found that such wound-induced hydrogen peroxide triggers a protein, called Lyn, that routes white blood cells and immune cells down a particular cellular pathway. While this process is ideal for healing infections, it can stimulate tumor growth and cause inflammation. By blocking Lyn, researchers reduced the recruitment of white blood cells to wounds. The finding could provide a better understanding of cancer and wound healing.

Cool Image: Moving Questions

Thu, 17 Nov 2011 08:00:00 EST

Two worm sperm shimmy across a microscope slide. Unlike most cells that rely on motor proteins to propel themselves forward, worm sperm use tiny fibers at their front ends. Putting the fibers together and taking them apart sets the cells in motion. In a new advance, researchers disassembled the worm sperm cell and rebuilt the parts used for motion so that they worked just as they do in a live cell. This approach may serve as a model for studying how other cells, including cancerous ones, get around.

Stem Cells Enable Adaptive Resizing of Fly Intestine

Thu, 17 Nov 2011 08:00:00 EST

Many tissues and organs, such as muscles or the liver, grow or shrink with usage. Even the intestine can be affected, shrinking to a third of its normal size in hibernating animals. Scientists have uncovered a mechanism by which this type of “organ adaptation” occurs. Working in fruit flies, they found that food intake causes the intestine to produce insulin, stimulating the division of intestinal stem cells and the expansion of the gut. The findings may suggest new approaches for treating obesity and diabetes in humans.

Protein Zelda Flips Mother’s Genes Off, Zygote’s Genes On

Thu, 17 Nov 2011 08:00:00 EST

For a short time, a fertilized egg (zygote) relies on maternal molecules before its own genetic processes kick in. Researchers have now identified a protein, called Zelda, that appears to coordinate this transition. Zelda turns off maternal genes and activates zygotic genes that form body parts, grow nerve cells and control other processes in the developing embryo. Although the research was done in fruit flies, the scientists suspect that molecules like Zelda also regulate the maternal to zygotic transition in humans. If so, studies of the protein could shed light on the molecular causes of certain birth defects.

Gut Bacteria May Play a Part in Cholesterol Drug’s Effectiveness

Thu, 17 Nov 2011 08:00:00 EST

Cholesterol-lowering drugs can be effective for some people, yet ineffective for others. A team of researchers recently discovered that the type of bacteria that reside in our gut may partly explain the variable response. The scientists found that three bile acids produced by certain bacteria in the gut appear to play a role in a person’s response to simvastatin, a common cholesterol-lowering medicine. These findings suggest that understanding the impact of the microbes that inhabit us on the medicines we take will be essential for personalizing medical therapies.

Impaired RNA Editing Linked to Fragile X Syndrome

Thu, 17 Nov 2011 08:00:00 EST

Disrupting the FMR1 gene causes Fragile X syndrome, the most common form of inherited intellectual disability and the most common genetic cause of autism. Now, new research in fruit flies shows that FMRP, the protein encoded by FMR1, is involved in RNA editing, a process that tweaks a gene’s sequence much like a newspaper editor might modify a reporter’s first draft. Fruit fly larvae lacking FMRP demonstrated impaired editing of certain RNAs and structural defects in the neuromuscular junction, an important communication channel between nerves and muscles. FMRP’s newly discovered role in RNA editing provides insight into the molecular basis of Fragile X syndrome and offers new strategies for treating the condition.

Cool Image: A Possible New Way to Ease Pain

Thu, 20 Oct 2011 08:00:00 EST

In this image, a mass of spinal nerve cells (green) includes the enzyme COX-2 (red). Drugs called NSAIDs—including ibuprofen (such as Advil®) and naproxen (such as Aleve®)—relieve pain and inflammation in part by acting on COX-2. Scientists thought that NSAIDs with a "left-handed" molecular structure do the hard work by stopping COX-2 from making prostaglandins. On the downside, NSAIDs can increase the risk of gastrointestinal and possibly cardiovascular problems. A recent study revealed that right-handed NSAIDs may reduce pain by stopping COX-2 from breaking down natural painkillers called endocannabinoids. The finding could lead to effective new drugs that have fewer side effects.

Why Some Flu Viruses are Species Specific

Thu, 20 Oct 2011 08:00:00 EST

Unlike A strains of the influenza virus, B strains usually only infect humans. Structural data may reveal the basis for this species specificity. Using X-ray crystallography, researchers created a three-dimensional snapshot of an influenza B virus protein bound to a human host protein. They found that only human and non-human primate versions of the protein—not those from other species—have a unique feature that makes this binding possible. The discovery could offer new insights into how influenza A strains infect and cross species, allowing them to mutate into more virulent forms, as well as aid in the development of flu-fighting drugs.

Genetic Information Sheds Light on Family’s Disease Risks

Thu, 20 Oct 2011 08:00:00 EST

It may one day become routine practice for doctors to review a patient’s genetic information before writing a prescription. Scientists recently studied a family of four’s genome sequences to better understand their genetic predisposition to diseases, including blood clotting. Using computational tools, the researchers compared the family members’ genomes to genetic data from people with similar ethnic backgrounds. They located variants associated with blood clotting and determined the exact dosage of a medicine taken by the father to prevent blood clots and predicted the dosage the daughter could one day need. These studies may bring doctors closer to personalizing medical treatments for patients.

Switching Off Cancer

Thu, 20 Oct 2011 08:00:00 EST

A challenge faced by cancer drug developers is that many candidates also affect normal cells, causing unwanted side effects. Working with human cells, a team of scientists sidestepped this problem by engineering a protein switch that only gets flipped in cancer cells. When one part of the toggle detects a protein found in cancer cells, it activates the other part—an enzyme that converts an inactive compound into a drug that kills the cells. While the technique needs more testing, it represents a novel way to approach the design of anti-cancer medicines.

Nobel Prize for Research on Immune System

Thu, 20 Oct 2011 08:00:00 EST

NIGMS grantee Bruce Beutler will share the 2011 Nobel Prize in physiology or medicine with two other scientists for research into how the body senses and defends against bacteria, viruses and other invaders. Beutler discovered the long-sought trigger of the body’s first-response system. When this trigger, a protein called TLR4, senses foreign bacteria, it mobilizes defenses—including inflammation—to kill the microbes. Further work by Beutler and others has led to improved vaccines, immune-based cancer therapies and new approaches to treating chronic inflammatory diseases like rheumatoid arthritis and Crohn’s disease.

Cool Image: Microscopic Mood Rings

Thu, 15 Sep 2011 11:00:00 EST

These glowing capsules shine in stressful situations--literally. Called polymersomes, the round, man-made membranes are studded with light-emitting pigments called porphyrins. When the membrane encounters stress, like tension or heat, the pigments change their configuration. Since shape determines how the porphyrins absorb and release light, the pigments glow in different hues. Here, the stressed region is evident before the membrane ruptures. Only a few microns in size, these miniscule mood rings could be used in body scanning or injected into the bloodstream to provide clues about nearby stresses, such as arterial blockages. Image courtesy of Neha Kamat, University of Pennsylvania.

DeCYPORing a Genetic Disorder

Thu, 15 Sep 2011 11:00:00 EST

Scientists are a step closer to understanding, and possibly preventing, Antley-Bixler syndrome. Children born with the rare genetic disorder don't produce enough of an enzyme called CYPOR, resulting in facial deformities and ambiguous sex organs. New research has uncovered CYPOR's structure in humans, as well as the structural changes responsible for Antley-Bixler syndrome. The scientists showed in basic lab studies that the B-vitamin riboflavin can reverse the activity of defective CYPOR enzymes. Knowing CYPOR's structure will help them and others investigate riboflavin therapy's potential to prevent or treat the syndrome.

How Salmonella Succeeds

Thu, 15 Sep 2011 11:00:00 EST

The bacterium Salmonella infects about 1.4 million Americans every year, causing fevers, diarrhea and abdominal cramps. A new study shows that Salmonella uses a compound called beta lysine in its protein-modifying machinery, rather than the virtually universal alpha lysine. When genes coding for beta lysine were knocked out or replaced with the alpha version during experiments, Salmonella lost its ability to cause disease. This property makes the beta version, never before seen in protein synthesis, an attractive target for antibiotics.

The Flip Side of Synthesis

Thu, 15 Sep 2011 11:00:00 EST

One way to create complex molecules and medicines is to join simple chemical building blocks in repetitive reactions, like assembling Lego bricks. But until recently, this technique--iterative cross-coupling--has been limited to molecules with one type of polarity. Now chemists have developed a reverse-polarity version of the technique, opening doors to a whole new batch of building blocks. The approach helped the research team synthesize synechoxanthin, a powerful antioxidant potentially useful for human health.

Rise of the Virtual Rat

Thu, 15 Sep 2011 11:00:00 EST

At a new systems biology center in Milwaukee, lab rats are going virtual. Drawing on genetic data and tissue samples, researchers are creating computer models of how the rat cardiovascular system works in health and disease. The work will shed light on how genetics and environmental factors interact to cause disease, a question that has long puzzled scientists. The ultimate goal is to use genes to predict a rat's heart health, which could lead to a similar approach for predicting complex human health conditions like high blood pressure and heart failure.

Cool Video: How Cilia Do the Wave

Thu, 18 Aug 2011 12:00:00 EST

Thin, hair-like biological structures called cilia are tiny but mighty. Notice how they beat in synchronized, self-organized motion like an audience doing "the wave." Working together, cilia play essential roles in human health, such as sweeping debris from the lungs. But scientists haven't cracked the mechanism controlling how the structures beat in unison. Now researchers have created the first-ever artificial cilia using motor proteins, structural parts and a bundling compound. The models, which synchronize spontaneously, offer a new approach for studying cilia and other self-organizing processes. Video courtesy of Zvonimir Dogic.

New Uses for Old Drugs

Thu, 18 Aug 2011 12:00:00 EST

Developing a new drug and bringing it to market can take 15 years and cost over $1 billion. But new research shows that many medicines already on the market may have unexpected therapeutic uses. Using computers and public databases, researchers analyzed gene activity in diseased cells and in drug-treated cells. They looked for activity patterns that complemented each other, because therapies theoretically reverse activity in diseased cells. The study confirmed some known pairings and turned up new ones, like an anticonvulsant to treat Crohn's disease.

Plants with Rhythm

Thu, 18 Aug 2011 12:00:00 EST

A tiny plant called Arabidopsis thaliana just helped scientists unearth new clues about daily behavioral cycles called circadian rhythms. Investigating why Arabidopsis does its major stem-growing in the dark, researchers found that a trio of proteins—the "evening complex"—interacts in early evening to silence two genes that usually promote plant growth. When the complex's activity trails off a few hours before dawn, the plants start their nightly stem elongation. Often used as model organism, Arabidopsis can shed light on human processes, like cell division and embryonic development, that are governed by circadian rhythms.

Lighting up Internal Organs

Thu, 18 Aug 2011 12:00:00 EST

Colored fluorescent proteins from jellyfish and corals can give scientists a detailed look at cells and molecules, but using them to visualize organs in live mammals has been challenging. For instance, some proteins in the blood, like hemoglobin, absorb the visible light that standard glowing probes emit, masking their fluorescent colors. Using a bacterial protein, researchers have engineered a new fluorescent probe, dubbed iRFP, that emits near-infrared light. Since mammalian tissues are nearly transparent in this light, it's easy to peer inside of them. The nontoxic, noninvasive method with no radiation risk has great potential for whole-body imaging.

HIV on the Brain and A Light on Life's Rhythms

Thu, 18 Aug 2011 12:00:00 EST

In the 10th anniversary issue of Findings, read about George Hightower, a graduate student in California who uses DNA sequencing to investigate HIV, especially how the virus attacks the human brain to affect some people's ability to think and remember. Also meet Cara Altimus, a Maryland neuroscientist who probes how light and darkness regulate the body's master clock, which could help illuminate the effects of sleep loss. Catch a glimpse into these scientists' busy lives outside the lab as well.

Comments (0) - Read and Add your own Comments