Protein that delays cell division in bacteria may lead to the identification of new antibiotics

Scientists at Washington University have worked out how two bacterial strains delay cell division when food is abundant, an understanding that might be used to design drugs that stop division entirely

Levin lab

In a rapidly dividing chain of bacterial cells (top), constriction rings that will pinch the cells in two appear in red. The red doughnut to the bottom right of the image is a constriction ring seen head on rather than from the side. In the middle, an image of the constriction rings (red) has been overlaid on one of the cell walls (green), The bottom image shows the constriction rings (red) and the bacterial DNA (blue). Scientists at Washington University in St. Louis are learning exactly how the bacteria control the assembly of the constriction rings and thus the timing of cell division.

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Creating plants that make their own fertilizer

Washington University biologists are undertaking an ambitious project to engineer tiny nitrogen-fixing devices within photosynthetic cells.

James Byard/WUSTL

Nancy Duan (left), Michelle Liberton and Lingxia Zhao are members of Himadri Pakrasi’s team, which has taken the first proof-of-principle steps toward inserting the genes needed to fix nitrogen — otherwise found only in bacteria and the bacteria-like Archae — into the cells of crop plants.

Since the dawn of agriculture, people have exercised great ingenuity to pump more nitrogen into crop fields. Farmers have planted legumes and plowed the entire crop under, strewn night soil or manure on the fields, shipped in bat dung from islands in the Pacific or saltpeter from Chilean mines and plowed in glistening granules of synthetic fertilizer made in chemical plants.

No wonder biologist Himadri Pakrasi’s team is excited by the project they are undertaking. If they succeed, the chemical apparatus for nitrogen fixation will be miniaturized, automated and relocated within the plant so nitrogen is available when and where it is needed — and only then and there.

“That would really revolutionize agriculture,” said Pakrasi, PhD, the Myron and Sonya Glassberg/Albert and Blanche Greensfelder Distinguished University Professor in Arts & Sciences and director of the International Center for Advanced Renewable Energy and Sustainability (I-CARES) at Washington University in St. Louis.

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Blood-clotting disorders

New center to study bleeding disorders and clot formation

Researchers at Washington University School of Medicine have received a $9 million grant to investigate blood-clotting disorders. From heart attacks and strokes to uncontrolled bleeding, clotting disorders cause more deaths each year in the United States than all types of cancer combined.




Strands of a protein called von Willebrand Factor (orange) play a key role in blood clotting. Secreted by cells lining the blood vessels, the strands capture platelets and initiate the formation of blood clots



“Blood clots in veins and arteries remain one of the great killers,” says principal investigator J. Evan Sadler, MD, PhD, professor of medicine and chief of the Division of Hematology. “The goal of this grant is to shorten the time between a new discovery in blood clotting or bleeding disorders and the application of that knowledge to help patients.”

Washington University is one of only five universities across the country receiving funding from the National Heart, Lung, and Blood Institute (NHLBI) to support a new Translational Research Center in Thrombotic and Hemostatic Disorders.

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DBBS faculty member Lihong Wang receives $3.8 million NIH Director’s Pioneer Award.

Lihong Wang, PhD, has received a National Institutes of Health (NIH) Director’s Pioneer Award to explore novel imaging techniques using light that promise significant improvements in biomedical imaging and light therapy.

Lihong Wang

One of only 11 recipients of the highly competitive award, Wang was selected from among 600 applicants. The award supports individual scientists of exceptional creativity who propose pioneering — and possibly transforming — approaches to major challenges in biomedical and behavioral research, according to the NIH.

The award will provide Wang with a total budget of $3.8 million over five years.

Wang, the Gene K. Beare Distinguished Professor of Biomedical Engineering at Washington University in St. Louis, says his research will explore transporting light into the body’s tissues far beyond the classical penetration limits for high-sensitivity imaging and low-side-effect therapy.

“I am honored to have received this award from among such a competitive group,” Wang says. “This award will allow us the intellectual freedom and resources to develop a brand new technology. If successfully implemented, it would impact many disciplines of biomedicine with applications, including imaging, such as functional brain imaging and reporter gene imaging; sensing (oximetry and glucometry); manipulation (optogenetics and nerve stimulation); and therapy (photodynamic therapy and photothermal therapy).”

A leading researcher on new methods of cancer imaging, Wang has received more than 30 research grants as the principal investigator with a cumulative budget of more than $38 million. His research on non-ionizing biophotonic imaging has been supported by the NIH, National Science Foundation (NSF), the U.S. Department of Defense, The Whitaker Foundation and the National Institute of Standards and Technology.

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Scientists read monkeys’ inner thoughts

By decoding brain activity, scientists were able to “see” that two monkeys were planning to approach the same reaching task differently — even before they moved a muscle.

Moran/Pearce

In the classic center-out reaching task, a monkey reaches from a central location to targets on a circle surrounding the starting position. This task does not allow the neural encoding for hand position to be separated from the neural encoding for hand velocity. If the starting position varies, however, as in the task shown here, hand position and initial hand velocity can be disambiguated.

Anyone who has looked at the jagged recording of the electrical activity of a single neuron in the brain must have wondered how any useful information could be extracted from such a frazzled signal.

But over the past 30 years, researchers have discovered that clear information can be obtained by decoding the activity of large populations of neurons.

Now, scientists at Washington University in St. Louis, who were decoding brain activity while monkeys reached around an obstacle to touch a target, have come up with two remarkable results.

Their first result was one they had designed their experiment to achieve: they demonstrated that multiple parameters can be embedded in the firing rate of a single neuron and that certain types of parameters are encoded only if they are needed to solve the task at hand.

Their second result, however, was a complete surprise. They discovered that the population vectors could reveal different planning strategies, allowing the scientists, in effect, to read the monkeys’ minds.

By chance, the two monkeys chosen for the study had completely different cognitive styles. One, the scientists said, was a hyperactive type, who kept jumping the gun, and the other was a smooth operator, who waited for the entire setup to be revealed before planning his next move. The difference is clearly visible in their decoded brain activity.

The study was published in the July 19 advance online edition of the journal Science.

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Unraveling the Brain’s Process for Predicting the Future



Associate Professor Jeffrey M. Zacks studies
 the brain’s process for predicting the future. (David Kilper)


Every day we make thousands of tiny predictions — when the bus will arrive, who is knocking on the door, whether the dropped glass will break. Now researchers are unraveling the process by which the brain makes these prognostications.

Predicting the near future is vital in guiding behavior, says Jeffrey M. Zacks, PhD, associate professor of psychology.

“It’s valuable to be able to run away when the lion lunges at you, but it’s ­super valuable to be able to hop out of the way before the lion jumps,” he says.

Zacks and his colleagues believe that a good part of predicting the future is maintaining a mental model of what is happening now. Occasionally this model needs updating, especially when the environment changes unpredictably.

In the study, volunteers watched movies of everyday events such as washing a car or building a LEGO model. When researchers stopped the movie, participants predicted what would happen next.

Sometimes the movie stopped when a new occurrence was about to take place. Other times, the researchers stopped the movie in the middle of an event. They found that participants correctly ­predicted activity within the event more than 90 percent of the time; they correctly predicted across the event boundary less than 80 percent of the time.

Zacks says the experiments offer hope of targeting prediction-based ­updating mechanisms to better diagnose early stage neurological diseases and provide tools to help patients.

Read more about this study in the university’s Newsroom

World’s largest hunk of cancer genome data released

To speed progress against cancer and other diseases, the St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project has announced the largest release to date of comprehensive human cancer genome data for free access by the global scientific community.

The amount of information released more than doubles the volume of high-coverage, whole-genome data currently available from all human genome sources combined. This information is valuable not just to cancer researchers, but also to scientists studying almost any disease.

The release of this data was announced as a part of a perspective published online May 29 in Nature Genetics.

The 520 genome sequences released are matched sets of normal and tumor tissue samples from 260 pediatric cancer patients. The Pediatric Cancer Genome Project is expected to sequence more than 1,200 genomes by year’s end. Each sample is sequenced at a quality control level known as 30-fold coverage, ensuring maximum accuracy. The St. Jude and Washington University researchers are analyzing the genomic sequences to determine the differences between each child’s normal and cancerous cells to pinpoint the causes of more than a half-dozen of the most deadly childhood cancers, an effort which has already produced a number of key discoveries reported in top scientific journals.
 
“This effort has generated more discoveries than we thought possible,” says James Downing, MD, St. Jude scientific director who leads the project at St. Jude. “We want to make this information available to the broader scientific community so that, collectively, we can explore new treatment options for these children. By sharing the information even before we analyze it ourselves, we’re hoping that other researchers can use this rich resource for insights into many other types of diseases in children and adults,” he said.

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