Author: Elia Ben-Ari

avatar

Posts by Elia Ben-Ari

Posted on

Say Cheese

by
0 comments
Assorted cheeses
A biofilm of bacteria and fungi, commonly known as a rind, forms on the surface of traditionally aged cheeses. Credit: Elia Ben-Ari.

Biofilms—multispecies communities of microbes that live in and on us, and in the environment—are important for human health and the function of ecosystems. But studying these microbial metropolises can be challenging because many of the environments where they’re found are hard to replicate in the lab.

Enter cheese rinds. These biofilms of bacteria and fungi form on the surface of traditionally aged cheeses, and could serve as a system for understanding how microbial communities form and function. By sequencing DNA from the rinds of 137 artisan cheese varieties collected in 10 countries, Rachel Dutton and her colleagues at Harvard University identified three general types of microbial communities that live on their tasty study subjects. After individually culturing representatives of all the species found in the rind communities the scientists added them to a growth medium that included cheese curd. This approach allowed them to recreate the communities in the lab and use them to detect numerous bacterial-fungal interactions and patterns of community composition over time.

The scientists plan to use their lab-grown cheese rinds to study whether and how various microbes compete or cooperate as they form communities, as well as what molecules and mechanisms are involved. In addition to answering fundamental questions about microbial ecology, this cheesy research might ultimately yield insights that help fight infection-causing biofilms or lead to the discovery of new antibiotics.

Learn more:
Harvard University News Release Exit icon
Dutton Lab Exit icon

Posted on

On the Trail of Drug-Defying Superbugs

by
0 comments
Antibiotic-resistant strains of Staphlyococcus aureus bacteria (purple) have become the most common cause of skin infections seen in hospital emergency departments. Credit: NIH’s National Institute of Allergy and Infectious Diseases.
Antibiotic-resistant strains of Staphlyococcus aureus bacteria (purple) have become the most common cause of skin infections seen in hospital emergency departments. Credit: NIH’s National Institute of Allergy and Infectious Diseases.

In the United States alone, at least 2 million people each year develop serious infections with bacteria that have become resistant to the antibiotics we use to combat them, and about 23,000 die, according to the Centers for Disease Control and Prevention. Antibiotic resistance can turn once-manageable infections into “superbug” diseases that are difficult—and sometimes impossible—to treat.

Scientists funded by the National Institutes of Health are studying many aspects of antibiotic resistance, including how it spreads. Read this Inside Life Science article for just a few research examples and how the work could aid efforts to curb the emergence of resistance.

Posted on

Understanding Complex Diseases Through Computation

by
2 comments
Scientists developed a computational method that could help identify various subtypes of complex diseases. Credit: Stock image

Complex diseases such as diabetes, cancer and asthma are caused by the intricate interplay of genetic, environmental and lifestyle factors that vary among affected individuals. As a result, the same medications may not work for every patient. Now, scientists have shown that a computational method capable of analyzing more than 100 clinical variables for a large group of people can identify various subtypes of asthma, which could ultimately lead to more targeted and personalized treatments. The research team, led by Wei Wu Exit icon of Carnegie Mellon University and Sally Wenzel of the University of Pittsburgh, used a computational approach developed by Wu to identify several patient clusters consistent with known subtypes of asthma, as well as a possible new subtype of severe asthma that does not respond well to conventional drug treatment. If supported by further studies, the researchers’ proposed approach could help improve the understanding, diagnosis and treatment not just of asthma but of other complex diseases.

This work also was funded by NIH’s National Heart, Lung, and Blood Institute.

Learn more:
Carnegie Mellon University News Release Exit icon

Posted on

Basic Research Fuels Medical Advances

by and
0 comments
Genetic defect that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease. Credit: Ilyas Yildirim, Northwestern University.
Scientists revealed a detailed image of the genetic change that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease. Credit: Ilyas Yildirim, Northwestern University. View larger image

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.

Posted on

Anti-Clotting Drugs: The Next Generation

by
1 comment
Form of heparin
Scientists created a tailor-made form of the anti-clotting drug heparin that offers several advantages.
View larger image

The low molecular weight (LMW) form of the drug heparin is commonly used to prevent unwanted blood clots that can lead to heart attacks and strokes. It’s usually derived from pig intestines and normally cleared from the human body by the kidneys. In individuals with impaired kidney function, the drug can build up in the circulation and cause excessive bleeding. Impurities and the risk of contamination are also concerns with pig-derived heparin.

Now, Robert Linhardt of Rensselaer Polytechnic Institute and Jian Liu of the University of North Carolina at Chapel Hill have created a synthetic, tailor-made form of LMW heparin that offers several advantages over the animal-derived version, including alleviating the risk of contamination from natural sources. Studies in the test tube and in mice showed that the activity of this customized heparin molecule is easily reversible in cases of overdose or uncontrolled bleeding. And, since it is cleared from the body by the liver rather than the kidneys, this form of heparin would be safer for people with impaired kidney function. Additional research, including testing in humans, will be needed before this new version of LMW heparin can be considered for medical use.

This work also was funded by NIH’s National Heart, Lung, and Blood Institute.

Learn more:

Rensselaer Polytechnic Institute News Release Exit icon
University of North Carolina at Chapel Hill News Release
Linhardt Labs
Liu Lab

Posted on

Animal Cells ‘Reach Out and Touch’ to Communicate

by
0 comments
Cytonemes in the fruit fly tracheal system.
Threadlike cytonemes (at right) convey signals between cells in the developing fruit fly tracheal system. Credit: Sougata Roy, University of California, San Francisco. View larger image

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.

Learn more:

UCSF News Release Exit icon

Posted on

Targeting Toxic RNA Molecules in Muscular Dystrophy

by
0 comments
Genetic defect that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease. Credit: Ilyas Yildirim, Northwestern University.
Scientists revealed a detailed image of the genetic defect that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease. Credit: Ilyas Yildirim, Northwestern University. View larger image

Myotonic dystrophy type 2 (DM2) is a relatively rare, inherited form of adult-onset muscular dystrophy that has no cure. It’s caused by a genetic defect in which a short series of nucleotides—the chemical units that spell out our genetic code—is repeated more times than normal. When the defective gene is transcribed, the resulting RNA repeat forms a hairpin-like structure that binds to and disables a protein called MBNL1.

Now, research led by Matthew Disney of The Scripps Research Institute (TSRI), Florida Campus, has revealed the detailed, three-dimensional structure of the RNA defect in DM2 and used this information to design small molecules that bind to the aberrant RNA. These designer molecules, even in small amounts, significantly improved disease-associated defects in a cellular model of DM2, and thus hold potential for reversing the disorder.

Drugs that target toxic RNA molecules associated with diseases such as DM2 are few and far between, as developing such compounds is technically challenging. The “bottom-up” approach that the scientists used to design potent new drug candidates, by first studying in detail how the RNA structure interacts with small molecules, is unconventional, noted Jessica Childs-Disney of TSRI, who was lead author of the paper with Ilyas Yildirim of Northwestern University. But it may serve as an effective strategy for pioneering the use of small molecules to manipulate disease-causing RNAs—a central focus of the Disney lab.

This work also was funded by NIH’s National Cancer Institute.

Learn more:
The Scripps Research Institute News Release Exit icon
Disney Lab

Posted on

Meet Dave Cummings

by
0 comments
Dave Cummings. Credit: Marcus Emerson, PLNU.
Dave Cummings
Field: Environmental microbiology
Works at: Point Loma Nazarene University, San Diego, Calif.
Hobbies: Hiking, backpacking, fly-fishing
Dream home: One that doesn’t need a lot of work
Credit: Marcus Emerson, PLNU

In college, as a pre-med student majoring in biology and chemistry, Dave Cummings grew frustrated with the traditional “cookbook” approach to doing labs in his science classes. Turned off by having to follow step-by-step lab procedures that had little to do with scientific discovery, Cummings changed his major to English literature. Studying literature, he says, “helped me find myself” and taught him to think critically.

Ultimately, Cummings says, “I came to realize that it wasn’t the practice of medicine that got me excited, but the science behind it all.” He decided to pursue a graduate degree in biology and—after “knocking on a lot of doors”—was accepted at the University of Idaho, where he earned his master’s and doctoral degrees and discovered his passion for microbiology.

Today, Cummings applies his critical thinking skills to his work as professor of biology back at his alma mater, Point Loma Nazarene University (PLNU), a small university focused on undergraduate education. There he studies the role of urban storm water in spreading genes for antibiotic resistance in natural environments, and pursues his enthusiasm for training the next generation of scientists. He enlists his students in his research, giving them what he calls “real, live, on-the-ground” research experience that relatively few undergraduate students at larger universities receive.

Cummings’ Findings

Antibiotic resistance, which can transform once-tractable bacterial infections into diseases that are difficult or impossible to treat, is a major public health challenge of the 21st century. The most common way that bacteria become drug resistant is by acquiring genes that confer antibiotic resistance from other bacteria. Often, such drug resistance genes are found on small, circular pieces of DNA called plasmids that are readily passed from one species of bacteria to another.

Urban wetlands provide ideal conditions for bacteria to mingle, swap genes and spread antibiotic resistance, notes Cummings. He focuses on the wetlands around San Diego, which act as a giant mixing bowl for storm runoff, human sewage, animal waste, naturally occurring plant and soil microorganisms, and plasmids indigenous to the wetlands.

Cummings and his students examine sediment samples from these wetlands in search of plasmids that carry resistance genes. They’ve found that during winter rains, the San Diego wetlands receive runoff containing antibiotic-resistant bacteria and plasmids, which can persist at low, but detectable, levels into the dry summer months.

“We know that urban storm water carries with it a lot of antibiotic-resistant bacteria, and along with that the DNA instructions [or genes] that code for the resistance,” says Cummings. “We have solid evidence of genes encoding resistance to clinically important antibiotics washing … into coastal wetlands in San Diego.”

“We’re trying to understand the scope of the problem, and ultimately what threat that poses to human health,” he says. His concern is that the drug-defying bacterial genes will accumulate in the wetlands, and then “[find] their way back to us, where they will augment and amplify the problem of resistance.”

Precisely how resistance genes might move from the environment into people is not yet known. One way this could occur is through direct contact with contaminated water or sediment by anglers, swimmers, surfers and other recreational users. Fish, birds and insects could also transmit resistance genes from contaminated wetlands to humans.

“There is good evidence elsewhere that birds are important vectors of drug-resistant pathogens, and this is my favorite possibility,” says Cummings. “Hopefully someday we can test that hypothesis.”

Cummings’ studies, done in collaboration with Ryan Botts at PLNU and Eva Top at the University of Idaho, could reveal antibiotic resistance genes with the potential to move into new species of disease-causing bacteria and back into human populations. By identifying these genes and raising awareness of the problem, he hopes to aid future efforts to mitigate the spread of antibiotic resistance.

Posted on

Making Strides in Genomic Engineering of Human Stem Cells

by
1 comment
Genetically engineered human stem cells. Credit: Jeff Miller, University of Wisconsin-Madison.
Genetically engineered human stem cells hold promise for basic biomedical research as well as for regenerative medicine. Credit: Jeff Miller, University of Wisconsin-Madison.

Human pluripotent stem cells (hPSCs) can multiply indefinitely and give rise to virtually all human cell types. Manipulating the genomes of these cells in order to remove, replace or correct specific genes holds promise for basic biomedical research as well as medical applications. But precisely engineering the genomes of hPSCs is a challenge. A research team led by Erik Sontheimer of Northwestern University and James Thomson of the Morgridge Institute for Research at the University of Wisconsin-Madison developed a technique that could be a great improvement over existing, labor-intensive methods. Their approach uses an RNA-guided enzyme from Neisseria meningitidis bacteria—part of a recently discovered bacterial immune system—to efficiently target and modify specific DNA sequences in the genome of hPSCs. The technique could eventually enable the repair or replacement of diseased or injured cells in people with some types of cancer, Parkinson’s disease and other illnesses.

This work also was funded by NIH’s National Center for Advancing Translational Sciences.

Learn more:

Thomson Bio Exit icon

Posted on

New Door Opens in the Effort to Stave off Mosquito-Borne Diseases

by
1 comment
Mosquito net Pyrethroids are used in mosquito nets distributed around the globe. Credit: Kurt Stepnitz, Michigan State University.

In the past decade, mosquitoes in many countries have become increasingly resistant to pyrethroid insecticides used to fend off mosquito-borne diseases such as malaria and dengue fever. Now, Ke Dong of Michigan State University and her colleagues have discovered a second pyrethroid-docking site in the molecular doorways, or channels, that control the flow of sodium into cells. Pyrethroids paralyze and kill mosquitoes and other insects by propping open the door and causing the pests to overdose on sodium, a critical regulator of nerve function. By providing new insights on pyrethroid action at the molecular level—and how mutations in the dual docking sites cause resistance—the findings open avenues to better monitoring and management of insecticide resistance.

Learn more:
Michigan State University News Release Exit icon