Saturday, March 20, 2010

“Biology May Not Be So Complex After All, Physicist ... - Science Daily” plus 3 more

“Biology May Not Be So Complex After All, Physicist ... - Science Daily” plus 3 more

Biology May Not Be So Complex After All, Physicist ... - Science Daily

Posted: 20 Mar 2010 02:30 AM PDT

ScienceDaily (Mar. 19, 2010) — 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 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.

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?

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.

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."

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.

Story Source:

Adapted from materials provided by Emory University.

Journal Reference:

  1. Golan Bel, Brian Munsky, Ilya Nemenman. The simplicity of completion time distributions for common complex biochemical processes. Physical Biology, 2009; 7 (1): 016003 DOI: 10.1088/1478-3975/7/1/016003

Note: If no author is given, the source is cited instead.

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Would You Pay $20 for Access to a Breast Cancer Cure? - New York Times Blogs

Posted: 20 Mar 2010 08:50 AM PDT

It seems safe to describe Andrew Hessel as an unbridled optimist. After all, he's selling $20 shares in a journey towards a personalized cure for breast cancer, which he says could be feasible in the next few years.

Mr. Hessel serves as the managing director of the Pink Army Cooperative. This Canadian organization has set out to lower the cost of cancer treatments, while also making them more effective by embracing a new wave of synthetic biology technology (a field that was recently the subject of a piece in The New York Times Magazine).

In particular, the group hopes to build a relatively cheap virus in its labs that could be tweaked on an individual basis to hunt down and kill breast cancer cells.

While there are plenty of start-ups chasing this same, very challenging goal, Mr. Hessel has set up the first "biotech company that is owned by the people," as he puts it.

A payment of 20 Canadian dollars (about 20 American dollars at current exchange rates) will buy you a spot in this cooperative. That fee entitles you to have access to the cancer cure created by the cooperative — if the organization can solve a host of massive technological, legal and economic issues first, of course. Breast cancer patients receiving the cure would also have to pay extra money for tests and treatment.

"You would be getting drug development as a subscription service," Mr. Hessel said. "You have to be a member of the co-op to get access to the drug pipeline."

Since the cooperative is a not-for-profit entity, it would not seek to make money from the testing and procedures. Mr. Hessel pitches this approach, where members would own the intellectual property around a cure, as being in stark contrast to the norms of the biotech industry today.

"Right now, we have a biotech industry that can only go after multibillion-dollar drug blockbusters," Mr. Hessel said. "That limits what they can work on, and frankly, the biotech companies have made very little progress when it comes to curing cancer over the past few decades.

Mr. Hessel admits that his project hasn't made much progress itself so far. Recruiting members has been difficult. When I joined the co-op a couple of weeks ago so I could learn more about what it was telling members, I was Member No. 106.

Mr. Hessel said that he is planning on launching a large social networking campaign to drum up support. "If an onion ring can get 1 million Facebook backers, we can," he joked.

Mr. Hessel spent seven years working as a research operations manager for Amgen, one of the world's largest biotech companies. He left the company, in part due to frustrations about its approach to drug discovery.

Amgen, like most of its peers, continues to develop generalized drugs and then push them through the arduous approval process.

Mr. Hessel and others contend that current drug development fails to adapt to the rapid changes sweeping through biotech. The cost of sequencing genetic data continues to fall at exponential rates. Meanwhile, the tools needed for synthetic biology continue to fall in price as well, giving more people a means of basically typing out genetic code on a machine.

"The drugs coming to market today were started 10 years ago and are pre-genomic," Mr. Hessel said. "They are obsolete. We understand considerably more about living organisms now."

Under the Pink Army Cooperative's plan, the group will start with one breast cancer patient. It will pay to sequence the DNA of her tumor and compare that to her overall DNA profile.

Then, the company would need to program a virus to hunt down the woman's specific cancer cells.

"Five years ago, it would cost about $25 million for that kind of personalized therapy," Mr. Hessel said. "Today, it would cost about $2 million."

Companies trying out personalized medicine have had limited success thus far, and Mr. Hessel has tried to set the initial expectations low.

"The first time through, we will have basically a toy therapeutic," he said. "It won't kill the cancer very effectively. But we are out to prove and refine a process."

Mr. Hessel is convinced that people will succeed with this type of therapy and reduce the cost of personalized cures to the $5,000 range, possibly in a few years. The Pink Army Cooperative was set up to try to make sure the public has access to such cures, should they actually arrive.

People participating in this program will be encouraged to make their genetic data public so that the researchers could gather a large body of information around the breast cancer cells.

The legal questions around personalized medicine are not even close to being answered. But Mr. Hessel has decided to push forward and hope the legal chips fall in his favor.

"We're looking at a number of things," Mr. Hessel said. "What if I made the drug for you, but I don't expressly guarantee it do anything? And, if I am not actually selling anything to you, do I even have to worry about the approval process? These are some of the unanswered questions."

The group plans to begin sequencing its first patient once it secures $50,000 in donations.

"That's what it will take to get this rolling," he said. "That's when we will start on the open-source viral kernel design."

Dr. Rob Carlson, the author of "Biology is Technology: The Promise, Peril, and New Business of Engineering Life," has followed the synthetic biology movement closely and said there's merit behind Mr. Hessel's ideas.

Mr. Carlson said he did not know enough about the specifics of the Pink Army Cooperative's plans but agreed that this area of science appears to show great promise and that falling costs for the underlying technology are putting very powerful tools in the hands of entrepreneurs.

"If they're talking about $50,000 to get going, that seems entirely reasonable to me in terms of an experiment," Mr. Carlson said. "All of a sudden these types of approaches have become feasible."

Mr. Carlson added that the synthetic biology movement appears to be following the traditions of past technology movements, where do-it-yourself enthusiasts are pushing the limits of what's possible.

"It really seems to me that biology will follow along the path of everything else I can find, where this bubbles up from a garage setting one way or another," he said. "I mean, it could be different from cars, computers and aviation, but I haven't found any reason to believe it's different."

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Top home-school texts dismiss Darwin, evolution - Hattiesburg American

Posted: 20 Mar 2010 04:25 AM PDT

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The textbook delivers a religious ultimatum to young readers and parents, warning in its "History of Life" chapter that a "Christian worldview ... is the only correct view of reality; anyone who rejects it will not only fail to reach heaven but also fail to see the world as it truly is."

When the AP asked about that passage, university spokesman Brian Scoles said the sentence made it into the book because of an editing error and will be removed from future editions.

The size of the business of home-school texts isn't clear because the textbook industry is fragmented and privately held publishers don't give out sales numbers. Slatter said home-school material sales reach about $1 billion annually in the U.S.

Publishers are well aware of the market, said Jay Wile, a former chemistry professor in Indianapolis who helped launch the Apologia curriculum in the early 1990s.

"If I'm planning to write a curriculum, and I want to write it in a way that will appeal to home-schoolers, I'm going to at least find out what my demographic is," Wile said.

In Kentucky, Lexington home-schooler Mia Perry remembers feeling disheartened while flipping through a home-school curriculum catalog and finding so many religious-themed textbooks.

"We're not religious home-schoolers, and there's somewhat of a feeling of being outnumbered," said Perry, who has home-schooled three of her four children after removing her oldest child from a public school because of a health condition.

Perry said she cobbled together her own curriculum after some mainstream publishers told her they would not sell directly to home-schooling parents.

Wendy Womack, another Lexington home-school mother, said the only scientifically credible curriculum she's found is from the Maryland-based Calvert School, which has been selling study-at-home materials for more than 100 years.

Apologia and Bob Jones University Press say their science books sell well. Apologia's "Exploring Creation" biology textbook retails for $65, while Bob Jones' "Biology" Third Edition lists at $52.

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Chemical competition: Research identifies new mechanism ... - Science Centric

Posted: 20 Mar 2010 08:14 AM PDT

A Princeton University-led research team has discovered that protein competition over an important enzyme provides a mechanism to integrate different signals that direct early embryonic development. The work suggests that these signals are combined long before they interact with the organism's DNA, as was previously believed, and also may inform new therapeutic strategies to fight cancer.

The fought-over enzyme, known as the mitogen-activated protein kinase (MAPK), is found in all complex organisms, ranging from yeast to humans. MAPK signalling pathways, or chemical networks that involve the enzyme, are critical for normal development, and defects in these pathways can lead to severe developmental disorders and cancer.

During early embryonic development, a single undifferentiated cell becomes a complex and highly specialised organism containing a variety of different cell types arranged in very precise patterns. These patterns, which ensure that the body structures from head-to-tail and front-to-back develop correctly and in the appropriate places, are created when cells respond to a series of chemical signals from different signalling pathways. The different patterning signals received by any given cell are ultimately combined to govern its future fate and tell it what kind of cell it should become.

Until now, scientists believed these pathways operated largely independently of one another to produce protein signals that travelled to the nuclei of the embryo's cells where DNA is stored. There, coordination of these signals was thought to occur when they interacted with cell DNA to influence and control the expression of genes. Results published March 9 in the journal Current Biology, however, suggest that competition for the MAPK enzyme among proteins in different pathways influences which signals are sent to cells, establishing a biochemical mode of signal integration that adds a previously unrecognised layer of complexity and control to embryonic development.

'It appears that different proteins in different pathways are competing for the MAPK enzyme inside these living organisms,' said Stanislav Shvartsman, associate professor in the Department of Chemical Engineering and the Lewis-Sigler Institute for Integrative Genomics who earned his Ph.D. from Princeton in 1999. 'Since these proteins are fighting for the same limited resource - the enzyme - they indirectly control one another, which in turn coordinates the developmental signals.'

Conventional biology teaches that enzymes like MAPK act on certain molecules, called substrates, to regulate chemical reactions. The new findings are surprising because it appears that, through competition with one another, the substrates of MAPK are, in fact, influencing the enzyme's activity.

'In a way, it's like the tail wagging the dog,' Shvartsman said. 'The substrates are regulating the enzyme, and, by extension, mediating the chemical reactions.'

Eric Wieschaus, Princeton's Squibb Professor in Molecular Biology who received the 1995 Nobel Prize in medicine for his pioneering work in developmental biology, said, 'Their results argue convincingly that these signalling molecules are interacting with each other in a competitive way such that even before anything gets to the DNA, they've already made decisions. Essentially the decisions aren't just made in terms of DNA, but also in terms of proteins working together. This is, in a way, revolutionary.'

The research team, led by Princeton chemical engineering graduate student Yoosik Kim, focused its attention on the interaction between MAPK and two proteins involved in two different signalling pathways for head-to-tail pattern formation. The first of these proteins is part of the pathway that governs the development of the head. The second protein plays a significant role in the chemical circuit that controls the development of the ends of the embryo, including the tail.

Using special techniques to visualise whether the proteins had interacted with the MAPK enzyme, the team found that the relative amount of the first protein controlled how much enzyme was available to interact with the second protein. For example, in the portion of the embryo that would become the head, where the concentration of the first protein was high, much less enzyme was available to act on the second protein than at the other end of the embryo, where the tail would ultimately develop.

'This competition makes sure that the same enzyme signals are interpreted differently in the head and in the tail, thereby allowing for the integration of multiple signals,' Shvartsman said.

Based on how the enzyme interacted with the proteins in the head region of the embryo, the team predicted that a third protein also might be competing for the MAPK enzyme in that area. To test the hypothesis, research team members at the Institute for Medical Research Israel-Canada at Hebrew University in Jerusalem used a series of experimental techniques to verify that their proposed protein could bind to the enzyme, an ability that was previously unknown. These findings suggest that the competition model may provide a novel way to identify proteins that are involved in signalling pathways.

Beyond advancing the fundamental understanding of mechanisms that control embryonic patterning, the work has implications for how to target cancer cells, which often exhibit hyperactive MAPK signalling.

'According to our substrate competition idea, MAPK signalling activity directed toward any given substrate decreases when you introduce a competing substrate,' Kim said. 'In theory, you can lower the activity of MAPK if you introduce a protein whose sole function is to bind to MAPK and thus act as a competitive inhibitor of MAPK signalling to all other substrates.' This strategy might one day allow scientists to slow or stop MAPK signalling pathways in cancer cells by adding a protein that monopolises the MAPK enzyme, effectively disrupting the chemical circuitry of a cancer cell.

In future work, the researchers plan to conduct experiments to investigate competition among other proteins that bind to MAPK and to investigate how this competition for the MAPK enzyme manifests itself in other organisms. The group also intends to explore how certain proteins are able to outcompete other proteins for the enzyme's attention, perhaps by binding more strongly or efficiently to the molecule. In time, the group may expand its work to consider whether similar competition models affect the activity of different enzymes in other signalling pathways.

Source: Princeton University

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