Monday, March 1, 2010

“Biology may not be so complex after all, Emory physicist finds - Genetic Engineering News” plus 3 more

“Biology may not be so complex after all, Emory physicist finds - Genetic Engineering News” plus 3 more


Biology may not be so complex after all, Emory physicist finds - Genetic Engineering News

Posted: 01 Mar 2010 07:15 AM PST

Mar 1 2010, 10:20 AM EST

Biology may not be so complex after all, Emory physicist finds

EUREKALERT

Contact: Beverly Clark
beverly.clark@emory.edu
404-712-8780
Emory University

Biophysicist identifies parameters for biochemical networks, distills system behavior into simple equivalent dynamics

Centuries ago, scientists began reducing the physics of the universe into a few, key laws described by a handful of parameters. Such simple descriptions have remained elusive for complex biological systems until now.

Emory University biophysicist Ilya Nemenman has identified parameters for several biochemical networks that distill the entire behavior of these systems into simple equivalent dynamics. The discovery may hold the potential to streamline the development of drugs and diagnostic tools, by simplifying the research models.

The resulting paper, now available online, will be published in the March issue of Physical Biology.

"It appears that the details of the complexity of these biological systems don't matter, as long as some aggregate property, which we've calculated, remains the same," says Nemenman, associate professor of physics and biology. He conducted the analysis with Golan Bel and Brian Munsky of the Los Alamos National Laboratory.

'A beautiful result'

The simplicity of the discovery makes it "a beautiful result," Nemenman says. "We hope that this theoretical finding will also have practical applications."

He cites the air molecules moving about his office: "All of the crazy interactions of these molecules hitting each other boils down to a simple behavior: An ideal gas law. You could take the painstaking route of studying the dynamics of every molecule, or you could simply measure the temperature, volume and pressure of the air in the room. The second method is clearly easier, and it gives you just as much information."

Nemenman wanted to find similar parameters for the incredibly complex dynamics of cellular networks, involving hundreds, or even thousands, of variables among different interacting molecules. Among the key questions: What determines which features in these networks are relevant? And if they have simple equivalent dynamics, did nature choose to make them so complex in order to fulfill a specific biological function? Or is the unnecessary complexity a "fossil record" of the evolutionary heritage?

A KPR scheme

For the Physical Biology paper, Nemenman and co-authors investigated these questions in the context of a kinetic proofreading (KPR) scheme.

KPR is the mechanism a cell uses for optimal quality control as it makes protein. KPR was predicted during the 1970s and it applies to most cellular assembly processes. It involves hundreds of steps, and each step may have different parameters.

A key aggregate rate

Nemenman and his colleagues wondered if the KPR scheme could be described more simply. "Our calculations confirmed that there is, in fact, a key aggregate rate," he says. "The whole behavior of the system boils down to just one parameter."

That means that, instead of painstakingly testing or measuring every rate in the process, you can predict the error and completion rate of a system by looking at a single aggregate parameter.

Charted on a graph, the aggregate behavior appears as a straight line amid a tangle of curving ones. "The larger and more complex the system gets, the more the aggregate behavior is visible," Nemenman says. "The completion time gets simpler and simpler as the system size goes up."

In addition to the KPR scheme, the paper reports similar results for other biochemical kinetics networks, including a reversible linear pathway and a general multi-step completion process.

Simplified models

Nemenman is now collaborating with Emory theoretical biologist Rustom Antia, to see if the discovery can shed light on the processes of immune cells. In particular, they are interested in the malfunction of certain immune receptors involved in most allergic reactions.

"We may be able to simplify the model for these immune receptors from about 3,000 steps to three steps," Nemenman says. "You wouldn't need a supercomputer to test different chemical compounds on the receptors, because you don't need to simulate every single step just the aggregate."

Just as the discovery of an ideal gas law led to the creation of engines and automobiles, Nemenman believes that such simple biochemical aggregates could drive advancements in health.

For Emory University research news in the natural and social sciences: www.emory.edu/esciencecommons

Emory University is known for its demanding academics, outstanding undergraduate experience, highly ranked professional schools and state-of-the-art research facilities. Perennially ranked as one of the country's top 20 national universities by U.S. News & World Report, Emory encompasses nine academic divisions as well as the Carlos Museum, The Carter Center, the Yerkes National Primate Research Center and Emory Healthcare, Georgia's largest and most comprehensive health care system.


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If you take simvastatin to control cholesterol, watch out for ... - EurekAlert

Posted: 01 Mar 2010 05:42 AM PST

[ Back to EurekAlert! ] Public release date: 1-Mar-2010
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Contact: Cody Mooneyhan
cmooneyhan@faseb.org
301-634-7104
Federation of American Societies for Experimental Biology

New research published in the Journal of Leukocyte Biology suggests that simvastatin negatively impacts the immune system's ability to clear infection and control inflammation in the presence of bacteria

Simvastatin might help us control our cholesterol, but when it comes to infection, it's an entirely different story says a new research study published in the Journal of Leukocyte Biology (http://www.jleukbio.org). In the research report, scientists from Italy show that simvastatin delivers a one-two punch to the immune system. First it impairs the ability of specialized immune cells, called macrophages, to kill pathogens. Then, it enhances production of molecules, called cytokines, which trigger and sustain inflammation.

"Statins are key drugs in the primary and secondary prevention of cardiovascular disease," said Cosima T. Baldari, Ph.D., a scientist from the Department of Evolutionary Biology at the University of Siena in Siena, Italy, who was involved in the research. "Our understanding of how these drugs affect the immune system should help maximize the benefits of these excellent drugs."

To make this discovery, the researchers conducted experiments using human cells and then followed up by conducting additional experiments in mice. They used human macrophages derived from blood samples of healthy donors and murine (mouse) macrophages. The macrophages were incubated with Staphlococcus aureus, a pathogen commonly found on the skin and in the upper airways. Once the infection manifested, researchers analyzed the bactericidal response of macrophages treated with simvastatin. Results showed that the treated macrophages were significantly impaired in both the removal of the pathogen and related cell debris and the killing of ingested bacteria compared to untreated cells. Additionally, the treated cells produced higher amounts of cytokines, which are responsible for triggering and sustaining inflammation. The same experiment was conducted in vivo, using mouse models, with similar results.

"Statins are lifesavers, but there might be room for improvement," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "Studies like this help pave the way for researchers to develop newer versions of drugs like statins that are more specific for their intended effect increasing the benefits of these pharmaceuticals."

The Journal of Leukocyte Biology (http://www.jleukbio.org) publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.



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Insect Character Recognition: Computers See Bees Like We Can’t - Wired News

Posted: 01 Mar 2010 06:32 AM PST




Studying animal behavior used to mean traveling into the wild and making detailed notes about gorillas. Now, biologist-coders are figuring out how to use computer vision techniques to convert the myriad motions of creatures big and small into crunchable data.

Researchers are figuring out how track the movements of insects like Drosophila, the fruit fly, in order to answer the question: How do we define behavior?

"A fundamental problem that we haven't done that much work on in biology is quantifying behavior," said Kristin Branson, a fellow at Howard Hughes Medical Institute's Janelia Farm Research Campus. "We have a much better handle on the very low-level things, molecular, genetic, and neural than we do at the global, large-scale level of behavior."

We know what behavior is: It's what animals do. But quantifying it isn't easy, even for tiny creatures with equally tiny brains. Big data came to branches of science like particle physics many years ago, but some realms of biology have remained resistant to the computational techniques that mark so many other disciplines. The data for a lot of behavioral biology remains simple human observations — or results from ingenious Rube Goldbergian experimental apparatus. Either way, it's hard to do what Branson calls high-throughput behavioral experiments.

So, while researchers mapped the fruit fly's genome in 2000 and know its genetics better than almost any other creature, the relationship between its genes, its brain, and its behavior is still hard to understand.

At Janelia, Branson's lab head, Gerry Rubin, is mapping out the circuits in the fruit fly brain. His team has created thousands of transgenic flies that allow them to test the individual circuits. But while we know what we've done, it's hard to tell what it makes the the flies do.

Let's say some genetic change is made to the fruit flies and they chase each other around 20 percent more often than an unaltered specimen. If you're the fly, that's the an important change, but how could a human researcher ever detect that 20 percent? It's not like counting how many times a monkey mother nurses.

"How do we say in a quantitative way how the behavior has changed?" Branson said. "You wouldn't notice that if you were just watching."

To solve that problem, Branson and collaborators in Michael Dickinson's lab at Caltech, where she was a postdoc, built the Caltech Multiple Fly Tracker. It's a piece of software that converts infrared video of up to 50 flies inside a special arena into movement data. The flies become small triangles in space and their behavior is plotted and recorded.

Another Dickinson lab postdoc, Andrew Straw, has even designed a 10-camera system he calls Flydra to track free moving, flying insects.

Some of what they've found is odd and unexpected. After recording male and female flies at Caltech, they mined the data for interesting differences between them.

"And if you looked at how often the fly turned, you could tell the gender of the fly with better than 90 percent accuracy," Branson said.

It's unclear why such a behavioral difference exists, but it does, and likely always has, hidden within the masses of data that our eyes receive when we watch a bunch of flies moving around.

All sorts of other behaviors emerge from the data, if you just watch for long enough.

"Fruit flies may not be as interesting as gorillas on the surface to humans. They just seem like little gnat sized things," said Serge Belongie, a computer vision specialist at the University of California San Diego, who was Branson's PhD advisor. "But you run this tracker long enough and there is some pretty interesting courtship competitiveness behavior. It's basically reality TV for fruit flies with some interesting stuff happening."

"We're finding subtle differences between individual flies now," Branson agreed. "If you're being not very technical about things, you can say that these flies have different personalities. In biology we try not to do it, but it's a fun way to think of it."

While computer vision is more familiar to people as the technology behind Optical Character Recognition or social media applications, it may work better with animal tracking than it does in some other settings. That's because researchers can design experiments that make acquiring clean data easier.

By designing the algorithms and the image acquisition apparatus together, it makes the most difficult computer vision problems disappear.

"If you think about people tracking, you can solve it at the 80 percent solved level because you don't have complete control of your environment," Branson said. "I want things to work at 99 or 100 percent. I feel like we can really solve the problem well enough that people will use these programs, and it will be a very clean solution."

While Branson's work qualifies as basic science, computer vision insect monitoring could have more immediate implications. Take beekeeping, which has been plagued by colony collapse disorder. Intel researcher Lily Mummert, a backyard apiarist, built a tracking tool that could identify bees coming and going from her own hive. Counting the number of bees coming into and out of it, and perhaps some other data, could yield important insights about the life and times of a beehive, she said.

Ideally, all the equipment could be miniaturized and stuck into a little unit that would beam data up.

"I'd like to see a little unit, a camera, full on board processor, and a little wireless transmitter so you could just mule off the count," Mummert said. "That thing could be a really versatile platform for all kinds of environmental monitoring. You could apply it to bees, you could apply it to anything."

All kinds of insect and animal monitoring experts got together for a workshop in late 2008, and they plan to do it again this year in Istanbul during the International Conference on Pattern Recognition.

With video cameras and computational ability getting cheaper and better, quantifying animal behavior will undoubtedly improve. It's possible that before too long, there will be a new encyclopedia of knowledge on the biology block: the behaviorome.

WiSci 2.0: Alexis Madrigal's Twitter, Tumblr, and green tech history research site; Wired Science on Twitter and Facebook.

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Local residents present research - Press & Sun-Bulletin

Posted: 01 Mar 2010 04:23 AM PST

Wilkes University students Naseem Mian and Jay Shah presented their scientific research at the American Society of Plant Biologists in Honolulu, Hawaii.

Their first project dealt with the differential gene regulation in Japonica and Indica rice and their F1 hybrids. Their second project dealt with antisense transcripts of light-regulated rice genesat. The information was offered in a special session for undergraduates and also in two general sessions for all scientists. The students were accompanied by Dr. William Terzaghi, a Wilkes University professor of biology.

Mian, a biochemistry major, is a resident of Johnson City. Shah, a biology major, is a resident of Vestal.

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