(Press-News.org) Michael Woods
m_woods@acs.org
504-670-4707 (New Orleans Press Center, April 5-10)
202-872-6293
American Chemical Society
A molecular 'superglue' based on flesh-eating bacteria
NEW ORLEANS, April 11, 2013 — In a classic case of turning an enemy into a friend, scientists have engineered a protein from flesh-eating bacteria to act as a molecular "superglue" that promises to become a disease fighter. And their latest results, which make the technology more versatile, were the topic of a report here today at the 245th National Meeting & Exposition of the American Chemical Society, the world's largest scientific society.
"We've turned the tables and put one kind of flesh-eating bacterium to good use," said Mark Howarth, Ph.D., who led the research. "We have engineered one of its proteins into a molecular superglue that adheres so tightly that the set-up we used to measure the strength actually broke. It resists high and low temperatures, acids and other harsh conditions and seals quickly. With this material we can lock proteins together in ways that could underpin better diagnostic tests — for early detection of cancer cells circulating in the blood, for instance. There are many uses in research, such as probing how the forces inside cells change the biochemistry and affect health and disease."
Howarth's team at the University of Oxford in the United Kingdom genetically engineered the glue from a protein, FbaB, that helps Streptococcus pyogenes (S. pyogenes) bacteria infect cells. S. pyogenes is one of the microbes that can cause the rare necrotizing fasciitis, or flesh-eating bacteria syndrome, in which difficult-to-treat infections destroy body tissue.
They split FbaB into two parts, a larger protein and a smaller protein subunit, termed a peptide. Abbreviating S. pyogenes as "Spy," they named the small peptide "SpyTag" and the larger protein "SpyCatcher." The gluing action occurs when SpyTag and SpyCatcher meet. They quickly lock together by forming one of the strongest possible chemical bonds. SpyCatcher and SpyTag can be attached to the millions of proteins in the human body and other living things, thus gluing proteins together.
In an advance reported at the meeting, Howarth described how Jacob Fierer, a graduate student on the research team, greatly reduced the size of the SpyCatcher part of the technology. That achievement makes the technology more flexible, enabling scientists to connect proteins into new architectures, he said.
One of the applications on the horizon involves testing the technology as a new way to detect "circulating tumor cells," or CTCs. Tumors shed these cells into the bloodstream, where they may act as seeds, spreading or metastasizing cancer from the original site to other parts of the body. That spreading is the reason why cancer is such a serious health problem. Detecting CTCs is an active area of research worldwide because of its potential for early diagnosis of cancer — from blood samples rather than biopsies — and determining when new treatments may be needed to prevent the disease from spreading.
Howarth said that the Spy technology has advantages over other molecular gluing systems that are available. SpyCatcher and SpyTag, for instance, can glue two proteins together at any point in the protein. "That flexibility allows us many different ways to label proteins and gives us new approaches to assemble proteins together for diagnostic tests," Howarth explained.
Howarth and colleagues are working with Isis Innovation, the University of Oxford's technology transfer company, to find potential partners to bring the Spy system to the market.
INFORMATION:
The researchers acknowledge funding from the Clarendon Fund.
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Abstract
Peptide interactions are nearly always weak and reversible, limiting application of peptides for assembly and control of biomolecules. We have designed tools enabling irreversible peptide interaction, based on a special feature of the chemistry of the human pathogen Streptococcus pyogenes. By rational engineering of a protein from this bacterium involved with host invasion, we obtained a peptide tag (SpyTag) bearing a carboxylic acid side-chain which spontaneously reacts with an amine side-chain, to form an amide bond locking the peptide to the protein partner (SpyCatcher). This reaction is rapid, high-yielding, genetically encodable and specific on cells. Complementation of this split protein has been analyzed by NMR and advanced by rational and library-based engineering. Applications of this protein padlock will be presented to show new possibilities for mammalian cell imaging, for enhancing enzyme function, and for controlling force within living cells, such as at chromosome segregation.
END
Michael Woods
m_woods@acs.org
504-670-4707 (New Orleans Press Center, April 5-10)
202-872-6293
American Chemical Society
Cost-saving measure to upgrade ethanol to butanol -- a better alternative to gasoline
NEW ORLEANS, April 11, 2013 — Scientists today reported a discovery that could speed an emerging effort to replace ethanol in gasoline with a substantially better fuel additive called butanol, which some experts regard as "the gasoline of the future." Their report on this discovery, which holds potential to reduce the costs of converting ethanol factories ...
Gastric bypass surgery can drastically reduce the body weight of obese individuals in a short timeframe. For reasons that are not entirely clear, the surgery also leads to early remission of type 2 diabetes in the vast majority of patients. Researchers report online April 11 in Cell Reports, published by Cell Press, the discovery of gene-expression alterations in individuals who underwent the surgery compared with obese individuals who did not.
"We provide evidence that in severely obese people, the levels of specific genes that control how fat is burned and stored in ...
Chronic liver failure is a major health problem that causes about one million deaths around the world each year. A study published April 11th by Cell Press in the journal Cell reveals a new type of screen for identifying genes that promote liver repair in mouse models of both acute and chronic liver disease. The study shows that the MKK4 gene could be a promising therapeutic target to enhance liver regeneration and provides a blueprint for future studies aimed at discovering new therapies for liver disease.
"It is now conceivable to develop specific pharmacological inhibitors ...
Slow oscillations in brain activity, which occur during so-called slow-wave sleep, are critical for retaining memories. Researchers reporting online April 11 in the Cell Press journal Neuron have found that playing sounds synchronized to the rhythm of the slow brain oscillations of people who are sleeping enhances these oscillations and boosts their memory. This demonstrates an easy and noninvasive way to influence human brain activity to improve sleep and enhance memory.
"The beauty lies in the simplicity to apply auditory stimulation at low intensities—an approach that ...
Mutations found in individuals with autism block the action of molecules made by the brain that act on the same receptors that marijuana's active chemical acts on, according to new research reported online April 11 in the Cell Press journal Neuron. The findings implicate specific molecules, called endocannabinoids, in the development of some autism cases and point to potential treatment strategies.
"Endocannabinoids are molecules that are critical regulators of normal neuronal activity and are important for many brain functions," says first author Dr. Csaba Földy, of ...
An annual report from the American Cancer Society finds continuing challenges in changing behaviors and risk factors in order to reduce suffering and death from cancer. The report, Cancer Prevention & Early Detection Facts & Figures (CPED) 2013, outlines the current prevalence of tobacco use, obesity, physical inactivity, and the use of established screening tests, and emphasizes that social, economic, and legislative factors profoundly influence the individual health behaviors that contribute to cancer risk.
Since 1992, the American Cancer Society has published CPED ...
Researchers at the University of California, San Diego School of Medicine have identified a previously unknown biological mechanism involved in the regulation of pancreatic islet beta cells, whose role is to produce and release insulin. The discovery suggests a new therapeutic target for treating dysfunctional beta cells and type 2 diabetes, a disease affecting more than 25 million Americans.
Writing in the April 11, 2013 issue of Cell, Jerrold M. Olefsky, MD, associate dean for scientific affairs and distinguished professor of medicine, and colleagues say a transmembrane ...
VIDEO:
Ph.D. Student Arvid Guterstam explains how he and his colleagues at Karolinska Institutet in Sweden can evoke the illusion of having a phantom hand in non-amputated individuals.
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The sensation of having a physical body is not as self-evident as one might think. Almost everyone who has had an arm or leg amputated experiences a phantom limb: a vivid sensation that the missing limb is still present. A new study by neuroscientists at the Karolinska ...
Regulating alcohol outlet density, or the number of physical locations in which alcoholic beverages are available for purchase in a geographic area, is an effective strategy for reducing excessive alcohol consumption and associated harms. A new report from the Center on Alcohol Marketing and Youth (CAMY) at the Johns Hopkins Bloomberg School of Public Health documents how localities can address alcohol outlet density, and outlines the critical role of health departments and community coalitions in these efforts. The report, published in the journal Preventing Chronic Disease, ...
VIDEO:
The video as it appears in the JoVE article.
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On April 11th JoVE (Journal of Visualized Experiments) will publish a new video article by Dr. Aydogan Ozcan demonstrating how a cell phone camera can capture images from a fluorescent microscope and flow cytometer, which will make it possible for areas with limited resources to easily run tests such as checking for contaminated water and monitoring HIV positive patients.
In the new video ...
