machalek

About Alisa Zapp Machalek

Alisa, who’s trained in biochemistry, writes articles, fact sheets, and publications about a variety of areas that include genetics, pharmacology, chemistry, and the body’s response to traumatic injury. She also edits Findings magazine, which aims to stoke students’ interest in biology and research careers.

Nobel Prize for Powerful Microscopy Technology

Fibroblasts
The cells shown here are fibroblasts, one of the most common cells in mammalian connective tissue. These particular cells were taken from a mouse. Scientists used them to test the power of a new microscopy technique that offers vivid views of the inside of a cell. The DNA within the nucleus (blue), mitochondria (green) and cellular skeleton (red) is clearly visible. Credit: Dylan Burnette and Jennifer Lippincott-Schwartz, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.

William E. Moerner was at a conference in Brazil when he learned he’d be getting a Nobel Prize in chemistry. “I was incredibly excited and thrilled,” he said of his initial reaction.

An NIGMS grantee at Stanford University, Moerner received the honor for his role in achieving what was once thought impossible—developing super-resolution fluorescence microscopy, which is so powerful it allows researchers to see and track individual molecules in living organisms in real time.

Nobel recipients usually learn of the prize via a phone call from Stockholm, Sweden, in early October. For those in the United States, the call typically comes between 2:30 a.m. and 5:45 a.m.

Every year, the NIGMS communications office prepares for the Nobel Prize announcements in physiology or medicine and chemistry, the categories in which our grantees are most likely to be recognized. If the Institute played a significant role in funding the prize-winning research, we work quickly to provide information and context to reporters covering the story on tight deadlines. We issue a statement, identify an in-house expert on the research and arrange interviews with reporters. It’s all to help get the word out about the research and the taxpayers’ role in supporting it.

This year’s in-house expert, Cathy Lewis, shared her thoughts on the prize to Moerner in an NIGMS Feedback Loop post. You can also read this year’s statement and see a full list of NIGMS-supported Nobel laureates.

Cool Image: Training Cells to Devour Dying Neighbors

A healthy cell that has ingested dying cells.
A healthy cell (green) that has ingested dying cells (purple). Credit: Toru Komatsu, University of Tokyo.

In this image, a healthy cell (green) has engulfed a number of dying cells (purple) just as a predator might ingest wounded or dying prey. A team of researchers is hoping to use this same strategy at the cellular level to help treat infection, neurodegenerative diseases or cancer.

Our bodies routinely use a process called phagocytosis to rid themselves of unhealthy cells. Takanari Inoue Exit icon at Johns Hopkins University and collaborators at the University of Tokyo set out to investigate the molecular underpinnings of phagocytosis. Their goal was to endow laboratory-grown human cells with phagocytotic skills, namely the ability to recognize, swallow and digest dying cells. The scientists tried to do this by inserting into the cells two molecules known to play a role in phagocytosis.

The engineered cells accomplished the first two tasks—they recognized and surrounded dying cells. But they didn’t digest what they’d engulfed. Now the researchers are looking for a molecular trigger to get the engineered cells to complete this last task.

Eventually, the scientific team aims to build artificial cells that are programmed to target and destroy abnormal cells, such as those ravaged by bacteria, cancer or other diseases.

Learn more:
Johns Hopkins News Release Exit icon
How Cells Take Out the Trash Article from Inside Life Science
Cellular Suicide: An Essential Part of Life Article from Inside Life Science

An Insider’s Look at Life: Magnified, an Airport Exhibit of Stunning Microscopy Images

Bubonic plague bacteria on part of the digestive system in a rat flea
What looks like pollen on petals is actually bubonic plague bacteria on the digestive spines of a flea, viewed through a powerful microscope. Credit: B. Joseph Hinnebusch, Elizabeth Fischer and Austin Athman, NIH’s National Institute of Allergy and Infectious Diseases.

Science. Art. Airports. I’ve never used those three words together before. But I’ve been doing it a lot lately while working on Life: Magnified, an exhibit of 46 striking scientific images created by scientists around the country using state-of-the-art microscopes.

The show is at Washington Dulles International Airport, where more than a million travelers will see it over its 6-month run. As our director said in a recent post on another NIGMS blog, “What a great way to share the complexity and beauty of biomedical science with such a large public audience!”

We’ve also set up an online gallery, where the colorful images can be viewed and freely downloaded for research, educational and news media purposes.

The project itself was quite an adventure. When we asked scientists to send us images, our fears of not getting enough attractive, high-resolution options were drowned by a deluge of more than 600 submissions. Then we worried how to sort through them all and make final selections. Doing so required several rounds of online viewing, various ranking systems and a panel of experts. Then the images were printed as large, digital negatives on transparency film.

Artist's rendition of a network diagram. Credit: Allison Kudla, Institute for Systems Biology.
The midnight installation of Life: Magnified involved five people (that’s me in pink), a ladder and lots of rags and glass cleaner. Credit: Woody Machalek.

Dulles is a pretty busy place, so we set up the exhibit when it was quietest—the middle of the night (10 p.m. to 1:30 a.m., to be exact). We swapped out images from the previous photography exhibit and installed the Life: Magnified ones in LED lightboxes mounted in the airport’s Gateway Gallery. It was an eerie and exhilarating feeling to be in a noiseless, nearly empty airport without heavy bags and a long walk to a departure gate.

Less than 12 hours later, I was surprised to receive an e-mail from someone who had passed through the exhibit and sent a few photos. He called the images “stunning.” Similar sentiments were expressed by Science Exit icon, NBC News online Exit icon, The Atlantic Exit icon, The Washington Post Exit icon, National Geographic Exit icon and other publications.

Now I’m being asked about next steps, including whether the exhibit will travel. We’re investigating a variety of options. For now, I hope you’re able to see the exhibit in person. If not, take a look at the images online and see which ones you enjoy most.

Learning How Mosquito-Borne Viruses Use Knot-like RNA to Cause Disease

A knot-like structure in a section of RNA from a flavivirus
A knot-like structure in RNA enables flaviviruses to cause diseases like yellow fever, West Nile virus and dengue fever, which threaten roughly half the world’s population. Credit: Jeffrey Kieft.

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.

Learn more:
University of Colorado News Release exit icon
Kieft Lab exit icon

Study Comparing Sepsis Treatment Methods Shows Equivalent Survival Rates

Doctors and a patient in a hospital
A 5-year, randomized clinical trial helped resolve a long-standing debate about how best to manage sepsis patients.

For years, doctors have debated the best ways to identify, predict and treat sepsis. The condition, which is usually triggered by infection, is marked by body-wide inflammation and can lead to a dangerous drop in blood pressure known as septic shock. Sepsis affects more than 800,000 people each year and kills about 20 to 30 percent of them. It’s the most expensive condition treated in U.S. hospitals, costing more than $20 billion a year.

Now, a nationwide, 5-year clinical trial that set out to compare three different treatment approaches has shown that survival of patients with septic shock was the same regardless of whether they received treatment based on structured, standardized medical plans (protocols) or the usual high-level standard of care. If patients were diagnosed shortly after the onset of sepsis and treated promptly with fluids and antibiotics, they did equally well whether they received treatment based on either of two specific protocols—one less invasive than the other—or got the usual, high-level care provided by the academic hospitals where the study was conducted.

According to the study’s leaders, the trial “helps resolve a long-standing clinical debate about how best to manage sepsis patients, particularly during the critical first few hours of treatment,” and shows that “there is not a mandated need for more invasive care in all patients.”

Learn more:
NIGMS News Release
University of Pittsburg News Release Exit icon
New England Journal of Medicine Article Exit icon
Sepsis Fact Sheet

Visualizing Vessels

Blood vessels in a mouse retina
Blood vessels in a mouse retina visualized using cutting-edge imaging technology. Credit: Tom Deerinck and Mark Ellisman, NCMIR.

For poets and lovers, the eyes are the windows of the soul. For scientists and doctors, blood vessels at the back of the eye are windows into many diseases.

Blood vessel abnormalities can indicate a variety of serious conditions such as atherosclerosis (hardening of the arteries), heart attacks and strokes. But most vessels are buried beneath skin and other tissues, making them difficult to examine without surgery.

There’s one exception—in the eye. Unlike anywhere else in the body, larger vessels on the retina at the back of the eye are directly visible through the pupil, requiring essentially only light and magnifying lenses to view.

These vessels are used to diagnose glaucoma and diabetic eye disease. Because they display characteristic changes in people with high blood pressure, some researchers hope retinal vessels might one day help predict an impending stroke, congestive heart failure or other diseases stemming from dangerously high blood pressure.

The medical importance of retinal vessels piqued the interest of scientists funded by the National Institutes of Health at the National Center for Microscopy and Imaging Research (NCMIR) at the University of California, San Diego, who captured this micrograph image of mouse retinal vessels.

Continue reading this new Inside Life Science article

Meet Jasmine Johnson and Gabe Vela

Jasmine Johnson and Gabriel 'Gabe' Vela
Jasmine Johnson and Gabriel “Gabe” Vela
Field: Genetics of sleep and obesity
Worked as researchers at: The Jackson Laboratory, Bar Harbor, Maine
Graduated from high school at: Rockdale Magnet School for Science and Technology in Conyers, Ga.
Now freshman at: Stanford University in Palo Alto, Calif. (Johnson) and Southern Polytechnic State University in Marietta, Ga. (Vela)
Fascinating fact: Johnson presented her research at the 2013 White House Science Fair
Credit: Joe Piergrossi

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 Exit icon 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.

Learn More
Article Exit icon about Johnson and Vela and other young researchers, from The Jackson Laboratory’s magazine The Search Exit icon.
Article about the work of Gary Churchill, from NIH’s Findings magazine.

Neanderthal DNA—Still Among Us

Map of Europe and Asia showing the presumed range of where Neanderthals lived.
For tens of thousands of years, Neanderthals lived in Europe and Asia (presumed range shown in blue) and interbred with humans, passing on some DNA to present-day people. Credit: Ryulong, Wikimedia Commons.
View larger image

Many of us have some Neanderthal genes. Before Neanderthals went extinct about 30,000 years ago, they interbred with humans living in Europe and Asia. Today’s descendants of those pairings inherited about 2 percent of their genomes from the big-brained hominids.

A research group led by David Reich at Harvard Medical School recently completed an analysis to determine the extent and identity of Neanderthal DNA in modern-day human populations. The group found that many traits in present-day people—including skin characteristics and susceptibility to various diseases—can be traced to Neanderthal DNA.

It also appears that, genetically speaking, Neanderthals and humans weren’t completely compatible. Based on the uneven distribution of Neanderthal DNA in today’s genomes, the scientists concluded that many of the male offspring of Neanderthal-human unions were infertile. In the animal world, this phenomenon is known as hybrid infertility, where the offspring of a male from one subspecies and a female from another have low or no fertility.

Studying human genes passed down through Neanderthals—as well as regions of the human genome notably devoid of Neanderthal DNA—provides an increasingly complete picture of the genetic landscape that contributed to health, disease and diversity among humans today.

Learn more:
Harvard Medical School News Release Exit icon
Evolution and Health Article from Inside Life Science
Reich Lab Exit icon

One Mutation Leads to Another—At Least in Yeast

DNA mutation. Credit: Stock image.
Newly discovered genetic effect in yeast could shed light on carcinogenesis. Credit: Stock image.

Cancer cells typically include many gene mutations, extra or missing genes, or even the wrong number of chromosomes. Scientists know that certain genetic changes lead to ones elsewhere. But they’ve had a chicken-and-egg problem trying to figure out which changes trigger which others—or whether mutations accumulate randomly in tumors.

New research led by J. Marie Hardwick Exit icon of Johns Hopkins University sheds light on the issue. She found that incapacitating a single gene in yeast cells—regardless of which gene it was—spurred mutations in one or two other genes. The process was anything but random: If, say, gene X was knocked out, yeast cells almost always developed a secondary mutation in gene Y. It’s as if knocking out one gene disrupts the genomic balance enough that the cell must alter a different gene to compensate.

Significantly, the secondary mutations—but not the original ones—caused altered yeast cell characteristics, including traits linked to cancer. Also, many of the secondary mutations occurred in genes associated with cancer in humans, further suggesting that these secondary changes might play a role in carcinogenesis.

This new information will help researchers better understand the chain of genetic events that lead to cancer. It might also prompt scientists to reevaluate years of research that attributed changes in cell behavior or appearance to a given gene knockout.

This work also was funded by NIH’s National Institute of Neurological Disorders and Stroke.

Learn more:
Johns Hopkins University News Release Exit icon

Genetic Discovery Could Enable More Precise Prescriptions

Prescription pad with DNA illustration on it. Credit: Jane Ades, NIH’s National Human Genome Research Institute.
New insight into the genes that affect drug responses may help doctors prescribe the medications and doses best suited for each individual. Credit: Jane Ades, NIH’s National Human Genome Research Institute.

Scientists know that variations in certain genes can affect the way a person responds to medications. New research by Wolfgang Sadee Exit icon at Ohio State University shows that drug responses also depend on previously overlooked parts of DNA—sections that regulate genes, but are not considered genes themselves. This study focused on an important enzyme abbreviated CYP2D6 that processes about one-fourth of all prescription drugs. Differences in the enzyme’s performance, which range from zilch to ultra-rapid, can dramatically alter the effectiveness and safety of certain medications. Researchers discovered two new genetic variants that impact CYP2D6 performance. One of these, located in a non-gene, regulatory region of DNA, doubles or even quadruples enzyme activity. Coupling these findings with genetic tests could help doctors better identify each patient’s CYP2D6 activity level, enabling more precise prescriptions. The findings also open up a whole new area of investigation into genetic factors that impact drug response.

This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Learn more:

Ohio State University News Release Exit icon
Using Genes to Guide Prescriptions Article from Inside Life Science Series