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Center for Theoretical Biological Physics

San Diego, CA, United States

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News Article | November 2, 2016
Site: www.sciencedaily.com

Protein pairs that control stimulus response in bacteria maintain a sensitive balance between interaction specificity and promiscuity, according to Rice University scientists. A computational model developed at Rice's Center for Theoretical Biological Physics will help biologists take advantage of the homologous nature of bacterial signaling systems to reveal the minimal mutations that allow a signaling protein to be efficiently reprogrammed to prefer a nonpartner signaling protein. Their open-access paper on the topic published online by the Oxford University Press journal Molecular Biology and Evolution will be featured on the cover of the December issue. The research led by Rice biophysicist and protein-folding pioneer José Onuchic, postdoctoral researcher Ryan Cheng and alumnus Faruck Morcos, now of the University of Texas at Dallas, expands upon previous work to model two-component systems that co-evolve amino acids at their binding surfaces to recognize each other. Those systems consist of proteins in bacterial cells that signal each other to sense and respond to stimuli. The new work extends the team's models to cover how mutating a signaling protein affects its interaction with its partner, as well as its interaction with other signaling systems. The extended model connects the fact that partner proteins are able to find each other in a crowd while also preventing unnecessary crosstalk. "We're showing for the first time that the method has enormous power for designing new stimulus-response mechanisms in organisms," said Onuchic, who predicted that the research will bring the disciplines of synthetic biology and systems biology closer together. Synthetic biologists engineer organisms like bacteria to produce chemicals or act as components in biological circuits. The Rice team's goal is to simplify their work by allowing them to model many possibilities before taking a project to the lab. "There are three goals in synthetic biology," Onuchic said. "The first is to force an organism to do something it's not supposed to do, like make insulin. The second is to change a mechanism to respond differently to a particular stimulus. There may be many reasons, and that may affect the phenotype of how an organism behaves. The third is to rewire different parts of an organism to understand what the parts are and what happens if we switch them. That's what our project is about," he said. "We want to understand sequence selection for two-component systems but we also want to demonstrate that our model can predict mutational phenotypes," said Cheng, the paper's lead author. "With this method, we're telling people that if they want 20 functional mutants, they can just pick the top 20 produced by our model. We're simply ranking them. Someone who wants to design novel interactions could use our model, select mutations and generate those mutations." Every cell contains thousands of two-component signaling proteins programmed to find each other and serve as sensors that trigger a cell to act, most often through the activation or repression of genes. "These systems have lots of response-raising kinases (the sensor component) and there's a lot of promiscuity," Onuchic said. "That's important, because a system doesn't have one copy of each thing; it has multiple copies of everything, and they're interacting with each other all the time. "Proteins are so similar, with minor variations between them, because you want them to see everything in their environments," he said. "If they were meant to be completely partner-specific, with no promiscuity, they would be very different from each other. The problem when you make these mutations is that you may offset the balance between interacting with its signaling partner versus interacting with other signaling proteins in a deleterious way." "We've constructed a co-evolutionary landscape that can predict which mutants lead to functional signaling in bacteria," Cheng said. Co-evolutionary landscapes allow for the prediction of how mutations affect signaling in bacteria and, consequently, an organism's fitness. He said the open-access model will make it faster and easier for researchers to plug in mutations and determine whether and how they will function. "Now we can apply these models to predict how mutations affect phenotypes (an organism's characteristics). The direct connection between sequence-level mutations and how they lead to the emergent properties of an organism is a holy grail of molecular biology," he said.


News Article | October 31, 2016
Site: www.eurekalert.org

Protein pairs that control stimulus response in bacteria maintain a sensitive balance between interaction specificity and promiscuity, according to Rice University scientists. A computational model developed at Rice's Center for Theoretical Biological Physics will help biologists take advantage of the homologous nature of bacterial signaling systems to reveal the minimal mutations that allow a signaling protein to be efficiently reprogrammed to prefer a nonpartner signaling protein. Their open-access paper on the topic published online by the Oxford University Press journal Molecular Biology and Evolution will be featured on the cover of the December issue. The research led by Rice biophysicist and protein-folding pioneer José Onuchic, postdoctoral researcher Ryan Cheng and alumnus Faruck Morcos, now of the University of Texas at Dallas, expands upon previous work to model two-component systems that co-evolve amino acids at their binding surfaces to recognize each other. Those systems consist of proteins in bacterial cells that signal each other to sense and respond to stimuli. The new work extends the team's models to cover how mutating a signaling protein affects its interaction with its partner, as well as its interaction with other signaling systems. The extended model connects the fact that partner proteins are able to find each other in a crowd while also preventing unnecessary crosstalk. "We're showing for the first time that the method has enormous power for designing new stimulus-response mechanisms in organisms," said Onuchic, who predicted that the research will bring the disciplines of synthetic biology and systems biology closer together. Synthetic biologists engineer organisms like bacteria to produce chemicals or act as components in biological circuits. The Rice team's goal is to simplify their work by allowing them to model many possibilities before taking a project to the lab. "There are three goals in synthetic biology," Onuchic said. "The first is to force an organism to do something it's not supposed to do, like make insulin. The second is to change a mechanism to respond differently to a particular stimulus. There may be many reasons, and that may affect the phenotype of how an organism behaves. The third is to rewire different parts of an organism to understand what the parts are and what happens if we switch them. That's what our project is about," he said. "We want to understand sequence selection for two-component systems but we also want to demonstrate that our model can predict mutational phenotypes," said Cheng, the paper's lead author. "With this method, we're telling people that if they want 20 functional mutants, they can just pick the top 20 produced by our model. We're simply ranking them. Someone who wants to design novel interactions could use our model, select mutations and generate those mutations." Every cell contains thousands of two-component signaling proteins programmed to find each other and serve as sensors that trigger a cell to act, most often through the activation or repression of genes. "These systems have lots of response-raising kinases (the sensor component) and there's a lot of promiscuity," Onuchic said. "That's important, because a system doesn't have one copy of each thing; it has multiple copies of everything, and they're interacting with each other all the time. "Proteins are so similar, with minor variations between them, because you want them to see everything in their environments," he said. "If they were meant to be completely partner-specific, with no promiscuity, they would be very different from each other. The problem when you make these mutations is that you may offset the balance between interacting with its signaling partner versus interacting with other signaling proteins in a deleterious way." "We've constructed a co-evolutionary landscape that can predict which mutants lead to functional signaling in bacteria," Cheng said. Co-evolutionary landscapes allow for the prediction of how mutations affect signaling in bacteria and, consequently, an organism's fitness. He said the open-access model will make it faster and easier for researchers to plug in mutations and determine whether and how they will function. "Now we can apply these models to predict how mutations affect phenotypes (an organism's characteristics). The direct connection between sequence-level mutations and how they lead to the emergent properties of an organism is a holy grail of molecular biology," he said. Co-authors of the paper are Olle Nordesjö and Samuel Flores of Uppsala University, Sweden; Ryan Hayes of the University of Michigan, Ann Arbor; and Herbert Levine, the Karl F. Hasselmann Professor of Bioengineering and a professor of physics and astronomy and of biochemistry and cell biology at Rice. Morcos is an assistant professor of biological sciences at the University of Texas at Dallas. Onuchic is Rice's Harry C. and Olga K. Wiess Chair of Physics and professor of physics and astronomy, of chemistry and biosciences. Onuchic and Levine are co-directors of the Center for Theoretical Biological Physics. The National Science Foundation, Uppsala University and the Swedish Foundation for International Cooperation in Research and Higher Education supported the research. Download the data sets and code used in the study at http://utdallas. This news release can be found online at http://news. Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,910 undergraduates and 2,809 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for happiest students and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl. .


News Article | March 3, 2017
Site: www.greencarcongress.com

« Oil Majors’ Costs Have Risen 66% Since 2011 | Main | Senate bill would enable sales of E15 and higher ethanol blends year round; RVP waiver » Scientists at Rice University, the University of Illinois at Urbana-Champaign and the University of Chile are proposing that quantum-controlled motion of nuclei, starting from the nanometer-size ground state of a molecule, can potentially overcome some of the difficulties of thermonuclear fusion by compression of a fuel pellet or in a bulk plasma. Their report on quantum-controlled fusion suggests that rather than heating atoms to temperatures found inside the sun or smashing them in a collider, it might be possible to nudge them close enough to fuse by using shaped laser pulses: ultrashort, tuned bursts of coherent light. Fusion reactions also can be induced by non-thermal means. For example, charged particle beams can be collided at appropriately high energy to carry out fusion reactions in the laboratory. Alternatively, fusion can be catalyzed by achieving a high spatial density, as happens for the nuclei within a muonic molecule. When a muon replaces the electron, it brings the nuclei ~200 times closer together than in an ordinary molecule, greatly enhancing the spontaneous nuclear reaction rate even at low temperature. In many ways, the ground state of such a molecule is the ideal situation for fusion because the phase space density of the reacting species takes on the largest possible value consistent with quantum mechanics. While greeted by much excitement when it was discovered in the 1950s, muon-catalyzed fusion still just falls a bit short of practicality because of the insufficient lifetime of the muon. Peter Wolynes of Rice, Martin Gruebele of Illinois and Illinois alumnus Eduardo Berrios of Chile simulated reactions in two dimensions that, if extrapolated to three, might just produce energy efficiently from deuterium and tritium or other elements. Their paper appears in the festschrift edition of Chemical Physical Letters dedicated to Ahmed Zewail, Gruebele’s postdoctoral adviser and a Nobel laureate for his work on femtochemistry, in which femtosecond-long laser flashes trigger chemical reactions. The femtochemical technique is central to the new idea that nuclei can be pushed close enough to overcome the Coulomb barrier that forces atoms of like charge to repel each other. When that is accomplished, atoms can fuse and release heat through neutron scattering. When more energy is created than it takes to sustain the reaction, sustained fusion becomes viable. The trick is to do all this in a controlled way, and scientists have been pursuing such a trick for decades, primarily by containing hydrogen plasmas at sun-like temperatures (at the US Department of Energy’s National Ignition Facility and the International Thermonuclear Experimental Reactor effort in France) and in large facilities. The new paper describes a basic proof-of-principle simulation that shows how, in two dimensions, a shaped-laser pulse would push a molecule of deuterium and tritium, its nuclei already poised at a much smaller internuclear distance than in a plasma, nearly close enough to fuse. … we performed quantum wavepacket propagation in a 2-D toy model of two field-bound nuclei in the presence of a time-dependent 800 nm laser pulse that was shaped to exert coherent control over the nuclear wavepacket. The collision probability is enhanced by about 3 orders of magnitude by the best coherent control pulse, and by up to 20 orders of magnitude relative to an electron-bound molecule. Since muonic fusion is already not far from break-even for net energy production, shaped VUV laser pulses, when they become available, could also be an efficient means of enhancing muonic fusion by coherent control. Wolynes said 2-D simulations were necessary to keep the iterative computations practical, even though doing so required stripping electrons from the model molecules. Without the electrons, it was still possible to bring nuclei within a small fraction of an angstrom by simulating the effects of shaped 5-femtosecond, near-infrared laser pulses, which held the nuclei together in a “field-bound” molecule. Because the model works at the quantum level—where subatomic particles are subject to different rules and have the characteristics of both particles and waves—the Heisenberg uncertainty principle comes into play. That makes it impossible to know the precise location of particles and makes tuning the lasers a challenge, Wolynes said. Wolynes said he and Gruebele, whose lab studies protein folding, cell dynamics, nanostructure microscopy, fish swimming behavior and other topics, have been thinking about the possibilities for about a decade, even though nuclear fusion is more of a hobby than a profession for both. Berrios, lead author of the paper, is a research scientist at the University of Chile, Santiago. Wolynes is the D.R. Bullard-Welch Foundation Professor of Science, a professor of chemistry, of biochemistry and cell biology, of physics and astronomy and of materials science and nanoengineering at Rice and a senior investigator at Rice's National Science Foundation-funded Center for Theoretical Biological Physics. Gruebele is the head of chemistry, the James R. Eiszner Endowed Chair in Chemistry and a professor of physics, biophysics and computational biology at Illinois.


News Article | December 16, 2016
Site: www.eurekalert.org

Physicists in Israel and the US have proposed a new type of travelling wave pattern -- one that can adapt to the size of physical system in which it is embedded - reporting the work in the New Journal of Physics. According to the theory, all of the key characteristics of the oscillation (the number of maxima, minima and nodes) remain the same, over a very wide range of host sizes, which turns out to be an exciting result. The scientists, David Kessler from Bar Ilan University and Herbert Levine from Rice University, share an interest in the dynamics of non-equilibrium systems - a topic that can often shed light on intricate processes such as those found in nature. "This work started as an attempt to generate an interesting example of wave patterns for a book we are writing on the overall field of pattern formation," said Herbert Levine of Rice University's Center for Theoretical Biological Physics. "Wave patterns are one of the general classes of non-equilibrium structures that can form when systems are driven far from equilibrium." Familiar examples include travelling wave patterns that describe the convection of fluid mixtures in response to temperature gradients. However, the researchers were drawn to the oscillatory behaviour displayed by the MIN system - a group of proteins involved in the cell division of bacteria such as E.Coli. "The MIN system is used to demarcate the center of a cell so that it divides into two symmetric daughters," said Levine. "Having a mechanism that allows the wave pattern to 'stretch' without changing all that much is a logical way to deal with this cell growth." By modelling the behaviour, the researchers found that - unlike other examples of pattern forming processes - the process at work here does not appear to be governed by a precise length scale. "Because of this, the waves seem to be more adaptable to the size of the region in which they live," Levine said. "This is an interesting finding from a pure physics perspective, but it may also have some implications from a biological point of view." The result could pave the way for new insights into how proteins are able to self-organize and accurately 'map' the surface of a cell as it grows. And, in principle, this knowledge may one day help in drug development by alerting scientists to ways of interfering with the spread of harmful bacteria.


News Article | December 16, 2016
Site: phys.org

According to the theory, all of the key characteristics of the oscillation (the number of maxima, minima and nodes) remain the same, over a very wide range of host sizes, which turns out to be an exciting result. The scientists, David Kessler from Bar Ilan University and Herbert Levine from Rice University, share an interest in the dynamics of non-equilibrium systems - a topic that can often shed light on intricate processes such as those found in nature. "This work started as an attempt to generate an interesting example of wave patterns for a book we are writing on the overall field of pattern formation," said Herbert Levine of Rice University's Center for Theoretical Biological Physics. "Wave patterns are one of the general classes of non-equilibrium structures that can form when systems are driven far from equilibrium." Familiar examples include travelling wave patterns that describe the convection of fluid mixtures in response to temperature gradients. However, the researchers were drawn to the oscillatory behaviour displayed by the MIN system - a group of proteins involved in the cell division of bacteria such as E.Coli. "The MIN system is used to demarcate the center of a cell so that it divides into two symmetric daughters," said Levine. "Having a mechanism that allows the wave pattern to 'stretch' without changing all that much is a logical way to deal with this cell growth." By modelling the behaviour, the researchers found that - unlike other examples of pattern forming processes - the process at work here does not appear to be governed by a precise length scale. "Because of this, the waves seem to be more adaptable to the size of the region in which they live," Levine said. "This is an interesting finding from a pure physics perspective, but it may also have some implications from a biological point of view." The result could pave the way for new insights into how proteins are able to self-organize and accurately 'map' the surface of a cell as it grows. And, in principle, this knowledge may one day help in drug development by alerting scientists to ways of interfering with the spread of harmful bacteria. Explore further: Scientists spot genes that make some sarcomas less aggressive More information: David A Kessler et al, Nonlinear self-adapting wave patterns, New Journal of Physics (2016). DOI: 10.1088/1367-2630/18/12/122001


News Article | March 2, 2017
Site: www.eurekalert.org

Controlled nuclear fusion has been a holy grail for physicists who seek an endless supply of clean energy. Scientists at Rice University, the University of Illinois at Urbana-Champaign and the University of Chile offered a glimpse into a possible new path toward that goal. Their report on quantum-controlled fusion puts forth the notion that rather than heating atoms to temperatures found inside the sun or smashing them in a collider, it might be possible to nudge them close enough to fuse by using shaped laser pulses: ultrashort, tuned bursts of coherent light. Authors Peter Wolynes of Rice, Martin Gruebele of Illinois and Illinois alumnus Eduardo Berrios of Chile simulated reactions in two dimensions that, if extrapolated to three, might just produce energy efficiently from deuterium and tritium or other elements. Their paper appears in the festschrift edition of Chemical Physical Letters dedicated to Ahmed Zewail, Gruebele's postdoctoral adviser and a Nobel laureate for his work on femtochemistry, in which femtosecond-long laser flashes trigger chemical reactions. The femtochemical technique is central to the new idea that nuclei can be pushed close enough to overcome the Coulomb barrier that forces atoms of like charge to repel each other. When that is accomplished, atoms can fuse and release heat through neutron scattering. When more energy is created than it takes to sustain the reaction, sustained fusion becomes viable. The trick is to do all this in a controlled way, and scientists have been pursuing such a trick for decades, primarily by containing hydrogen plasmas at sun-like temperatures (at the U.S. Department of Energy's National Ignition Facility and the International Thermonuclear Experimental Reactor effort in France) and in large facilities. The new paper describes a basic proof-of-principle simulation that shows how, in two dimensions, a shaped-laser pulse would push a molecule of deuterium and tritium, its nuclei already poised at a much smaller internuclear distance than in a plasma, nearly close enough to fuse. "What prevents them from coming together is the positive charge of the nuclei, and both of these nuclei have the smallest charge, 1," Wolynes said. He said 2-D simulations were necessary to keep the iterative computations practical, even though doing so required stripping electrons from the model molecules. "The best way to do it would be to leave the electrons on to help the process and control their motions, but that is a higher-dimensional problem that we -- or someone -- will tackle in the future," Wolynes said. Without the electrons, it was still possible to bring nuclei within a small fraction of an angstrom by simulating the effects of shaped 5-femtosecond, near-infrared laser pulses, which held the nuclei together in a "field-bound" molecule. "For decades, researchers have also investigated muon-catalyzed fusion, where the electron in the deuterium/tritium molecule is replaced by a muon," Gruebele said. "Think of it as a 208-times heavier electron. As a result, the molecular bond distance shrinks by a factor of 200, poising the nuclei even better for fusion. "Sadly, muons don't live forever, and the increased fusion efficiency just falls short of breaking even in energy output," he said. "But when shaped vacuum ultraviolet laser pulses become as available as the near-infrared ones we simulated here, quantum control of muonic fusion may get it over the threshold." Because the model works at the quantum level -- where subatomic particles are subject to different rules and have the characteristics of both particles and waves -- the Heisenberg uncertainty principle comes into play. That makes it impossible to know the precise location of particles and makes tuning the lasers a challenge, Wolynes said. "It's clear the kind of pulses you need have to be highly sculpted and have many frequencies in them," he said. "It will probably take experimentation to figure out what the best pulse shape should be, but tritium is radioactive, so no one ever wants to put tritium in their apparatus until they're sure it's going to work." Wolynes said he and Gruebele, whose lab studies protein folding, cell dynamics, nanostructure microscopy, fish swimming behavior and other topics, have been thinking about the possibilities for about a decade, even though nuclear fusion is more of a hobby than a profession for both. "We finally got the courage to say, 'Well, it's worth saying something about it.' "We're not starting a company ... yet," he said. "But there may be angles here other people can think through that would lead to something practical even in the short term, such as production of short alpha particle pulses that could be useful in research applications. "I'd be lying if I said that when we started the calculation, I didn't hope it might just solve mankind's energy problems," Wolynes said. "At this point, it doesn't. On the other hand, I think it's an interesting question that starts us on a new path." Berrios, lead author of the paper, is a research scientist at the University of Chile, Santiago. Wolynes is the D.R. Bullard-Welch Foundation Professor of Science, a professor of chemistry, of biochemistry and cell biology, of physics and astronomy and of materials science and nanoengineering at Rice and a senior investigator at Rice's National Science Foundation-funded Center for Theoretical Biological Physics. Gruebele is the head of chemistry, the James R. Eiszner Endowed Chair in Chemistry and a professor of physics, biophysics and computational biology at Illinois. This news release can be found online at http://news. Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,879 undergraduates and 2,861 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for happiest students and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl. .


News Article | December 8, 2016
Site: www.eurekalert.org

What could cancer cells and drug-resistant bacteria possibly have in common with Stone Age settlers of the Americas? They're all migratory, and at one time or other, each finds the going a bit easier in a specific direction. For cancer cells, the path of least resistance is often along tissue boundaries rather than through them, and studies have found that bacteria can become drug-resistant more quickly in nonhomogenous environments. In the case of humans settling America, a new study from Rice University finds that migration was easier moving east-west as opposed to north-south, largely because the knowledge needed to live in the same climate zones was easily transferable. The research is available online in the Journal of the Royal Society Interface. Lead researcher Michael Deem said he conceived the study while reading Jared Diamond's "Guns, Germs and Steel," a 1998 Pulitzer Prize-winning book that argued that differences in power and technology between human societies stem more from environmental and geographic factors than from intellectual, genetic or cultural attributes. "One hypothesis he put forward was that migration was more rapid in the east-west direction than in the north-south direction because the crops and animals people relied upon tended to remain the same if the people migrated east-west within climate zones and tended to change if they moved north-south between climate zones," said Deem, Rice's John W. Cox Professor in Biochemical and Genetic Engineering and a senior scientist at Rice's Center for Theoretical Biological Physics. "The idea is that it takes extra time and effort to develop the techniques and knowledge necessary to survive in a new climate, and that creates more of an obstacle to north-south migration. I thought that was really interesting, and I always wanted to do something a little more quantitative on that problem," he said. Deem, who chairs Rice's Department of Bioengineering and is a professor of physics and astronomy, specializes in using statistical mechanics to design computer simulations that accurately capture the complexity of nature. His work has led to mathematical laws of biology and includes computer models that predict how well next year's flu vaccine will work, how globalization affects the world economy and how the speed of biological evolution increases with time because of evolution. A common theme throughout Deem's research is "modularity," a feature of data that can be revealed through various techniques. For migrating bacteria, a specific gene could be a module of information, and an analogous module for the first humans in America would be specific knowledge about local environments or effective techniques for farming or raising animals. "A big aspect that we're interested in is how modularity accelerates the adaptation of biological systems, and more specifically in this case, how the modularity of knowledge interacts with asymmetry during migration," Deem said. "What we learn can be broadly applied, because the physical dynamics are similar in the case of the east-west verses north-south migration of people in the Americas and in the case of bacteria migrating in a Petri dish where there's a right-left versus up-down antibiotic gradient. One could also envision analogous scenarios with invasive species or metastatic cancer." In designing the model of human migration in the Americas, Deem and graduate student Dong Wang incorporated variables related to environment, the timing and speed of migration, knowledge creation and communication, genetics and the overall "fitness" or health of populations. The model predicts how populations expand across a 9-by-25 grid that simulates the length and approximate width of the Americas. Archaeological evidence shows that the first Americans arrived from Asia via a land bridge across the present-day Bering Strait during a glacial ice age about 20,000 years ago. In keeping with the dominant theory among archeologists, Deem and Wang's model begins with humans entering the Americas from the far north. "Once a population reaches the carrying capacity on their site, and the fitness is above a threshold, they will attempt to migrate to a new site," Wang said. "What we will see is that there is a front of migration, an east-west line that moves south over time." The likelihood of migration into an adjacent site depends partly on how similar the environment is, and the environment in the east-west direction changes less, on average, than it does north-south. "The more modular knowledge is, the easier it is to optimize, and the easier it is to transmit that information to other individuals and the easier it is to pioneer new sites," Deem said. "If tasks are interdependent -- perhaps the corpus of knowledge required to grow a particular crop also interacts with knowledge about how to make tools or when the seasons change -- the easier it is to pioneer new sites. The more things interact, the more difficult it is to optimize that problem, and that's a situation with less modularity of knowledge." Wang said the model was confirmed with empirical data where possible. "The model includes genetics, and we can examine the genes of individuals," he said. "That allows us to look at the genetic distance between different populations at different places and times, and when we compare those actual measures from the archeological record, we find that they match pretty well. Another empirical check is the actual rates of migration and the asymmetry of the rates of migration in the archeological record." Deem said the model is the first to both explicitly quantify the effect of modularity on fitness and examine how environmental asymmetry affects human migration. "We learned that Jared Diamond's idea makes sense," Deem said. "It is the case that when the asymmetry in the north-south direction of the environments is larger than in the east-west direction, then it is harder to migrate in the north-south direction." He and Wang will next focus on modifying the model to focus specifically on cancer metastasis. "In solid tumor cancers, for example, there's an asymmetry in the radial direction, away from the tumor versus on the surface of the tumor," Deem said. "There also is an asymmetry as the cells metastasize and go through different tissues in the body. So, there's an asymmetry along membranes versus through membranes, and there are recent empirical studies that provide new data that we can use to help examine the effect of these asymmetries in greater detail." The DOI of the Interfaces paper is: 10.1098/rsif.2016.0778 A copy of the paper is available at: http://rsif. New materials could slash energy costs for CO2 capture -- May 30, 2012 http://news. New way of predicting dominant seasonal flu strain -- Nov. 15, 2010 http://news. Forced evolution: Can we mutate viruses to death? -- Nov. 10, 2008 http://news. This release can be found online at news.rice.edu. Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,910 undergraduates and 2,809 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for happiest students and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl. .


News Article | December 8, 2016
Site: phys.org

For cancer cells, the path of least resistance is often along tissue boundaries rather than through them, and studies have found that bacteria can become drug-resistant more quickly in nonhomogenous environments. In the case of humans settling America, a new study from Rice University finds that migration was easier moving east-west as opposed to north-south, largely because the knowledge needed to live in the same climate zones was easily transferable. The research is available online in the Journal of the Royal Society Interface. Lead researcher Michael Deem said he conceived the study while reading Jared Diamond's "Guns, Germs and Steel," a 1998 Pulitzer Prize-winning book that argued that differences in power and technology between human societies stem more from environmental and geographic factors than from intellectual, genetic or cultural attributes. "One hypothesis he put forward was that migration was more rapid in the east-west direction than in the north-south direction because the crops and animals people relied upon tended to remain the same if the people migrated east-west within climate zones and tended to change if they moved north-south between climate zones," said Deem, Rice's John W. Cox Professor in Biochemical and Genetic Engineering and a senior scientist at Rice's Center for Theoretical Biological Physics. "The idea is that it takes extra time and effort to develop the techniques and knowledge necessary to survive in a new climate, and that creates more of an obstacle to north-south migration. I thought that was really interesting, and I always wanted to do something a little more quantitative on that problem," he said. Deem, who chairs Rice's Department of Bioengineering and is a professor of physics and astronomy, specializes in using statistical mechanics to design computer simulations that accurately capture the complexity of nature. His work has led to mathematical laws of biology and includes computer models that predict how well next year's flu vaccine will work, how globalization affects the world economy and how the speed of biological evolution increases with time because of evolution. A common theme throughout Deem's research is "modularity," a feature of data that can be revealed through various techniques. For migrating bacteria, a specific gene could be a module of information, and an analogous module for the first humans in America would be specific knowledge about local environments or effective techniques for farming or raising animals. "A big aspect that we're interested in is how modularity accelerates the adaptation of biological systems, and more specifically in this case, how the modularity of knowledge interacts with asymmetry during migration," Deem said. "What we learn can be broadly applied, because the physical dynamics are similar in the case of the east-west verses north-south migration of people in the Americas and in the case of bacteria migrating in a Petri dish where there's a right-left versus up-down antibiotic gradient. One could also envision analogous scenarios with invasive species or metastatic cancer." In designing the model of human migration in the Americas, Deem and graduate student Dong Wang incorporated variables related to environment, the timing and speed of migration, knowledge creation and communication, genetics and the overall "fitness" or health of populations. The model predicts how populations expand across a 9-by-25 grid that simulates the length and approximate width of the Americas. Archaeological evidence shows that the first Americans arrived from Asia via a land bridge across the present-day Bering Strait during a glacial ice age about 20,000 years ago. In keeping with the dominant theory among archeologists, Deem and Wang's model begins with humans entering the Americas from the far north. "Once a population reaches the carrying capacity on their site, and the fitness is above a threshold, they will attempt to migrate to a new site," Wang said. "What we will see is that there is a front of migration, an east-west line that moves south over time." The likelihood of migration into an adjacent site depends partly on how similar the environment is, and the environment in the east-west direction changes less, on average, than it does north-south. "The more modular knowledge is, the easier it is to optimize, and the easier it is to transmit that information to other individuals and the easier it is to pioneer new sites," Deem said. "If tasks are interdependent—perhaps the corpus of knowledge required to grow a particular crop also interacts with knowledge about how to make tools or when the seasons change—the easier it is to pioneer new sites. The more things interact, the more difficult it is to optimize that problem, and that's a situation with less modularity of knowledge." Wang said the model was confirmed with empirical data where possible. "The model includes genetics, and we can examine the genes of individuals," he said. "That allows us to look at the genetic distance between different populations at different places and times, and when we compare those actual measures from the archeological record, we find that they match pretty well. Another empirical check is the actual rates of migration and the asymmetry of the rates of migration in the archeological record." Deem said the model is the first to both explicitly quantify the effect of modularity on fitness and examine how environmental asymmetry affects human migration. "We learned that Jared Diamond's idea makes sense," Deem said. "It is the case that when the asymmetry in the north-south direction of the environments is larger than in the east-west direction, then it is harder to migrate in the north-south direction." He and Wang will next focus on modifying the model to focus specifically on cancer metastasis. "In solid tumor cancers, for example, there's an asymmetry in the radial direction, away from the tumor versus on the surface of the tumor," Deem said. "There also is an asymmetry as the cells metastasize and go through different tissues in the body. So, there's an asymmetry along membranes versus through membranes, and there are recent empirical studies that provide new data that we can use to help examine the effect of these asymmetries in greater detail." More information: Dong Wang et al. Modular knowledge systems accelerate human migration in asymmetric random environments, Journal of The Royal Society Interface (2016). DOI: 10.1098/rsif.2016.0778


News Article | November 10, 2016
Site: www.sciencedaily.com

Rice University scientists have uncovered new details about how a repeating nucleotide sequence in the gene for a mutant protein may trigger Huntington's and other neurological diseases. Researchers at Rice's Center for Theoretical Biological Physics used computer models to analyze proteins suspected of misfolding and forming plaques in the brains of patients with neurological diseases. Their simulations confirmed experimental results by other labs that showed the length of repeating polyglutamine sequences contained in proteins is critical to the onset of disease. The study led by Rice bioscientist Peter Wolynes appears in the Journal of the American Chemical Society. Glutamine is the amino acid coded for by the genomic trinucleotide CAG. Repeating glutamines, called polyglutamines, are normal in huntingtin proteins, but when the DNA is copied incorrectly, the repeating sequence of glutamines can become too long. The result can be diseases like Huntington's or spinocerebellar ataxia. The number of repeats of glutamine can grow as the genetic code information is passed down through generations. That means a healthy parent whose huntingtin gene encodes proteins with 35 repeats may produce a child with 36 repeats. A person having the longer repeat is likely to develop Huntington's disease. Aggregation in Huntington's typically begins only when polyglutamine chains reach a critical length of 36 repeats. Studies have demonstrated that longer repeat chains can make the disease more severe and its onset earlier. The paper builds upon techniques used in an earlier study of amyloid beta proteins. That study was the lab's first attempt to model the energy landscape of amyloid aggregation, which has been implicated in Alzheimer's disease. This time, Wolynes and his team were interested in knowing how the varying length of repeats -- as few as 20 and as many as 50 -- influenced how aggregates form. "The final form of the protein detected in people who have Huntington's disease is a macroscopic aggregate made of many molecules, much like an ice crystal formed out of water has many molecules in it," Wolynes said. "This process needs to start somewhere, and that would be with a nucleus, the smallest-size cluster that will then be able to finish the process and grow to macroscopic size. "People knew that the length of the repeats is correlated with the severity of a disease, but we wanted to know why that matters to the critical nucleus size," he said. Experiments had demonstrated that sequences of 20 repeats or less remained unfolded -- or "noodle-y," as Wolynes described them; they were able to clump into a nucleus only when four or more were gathered together in proximity. The researchers' simulations showed how sequences with 30 repeats or more are able to fold by themselves without partners into hairpin shapes, which are the building blocks for troublesome aggregates. Thus, for the longer sequences, even a single protein can begin the aggregation process, especially at high concentrations. The Rice team found that at intermediate lengths between 20 and 30 repeats, polyglutamine sequences can choose between straight or hairpin configurations. While longer and shorter sequences form aligned fiber bundles, simulations showed intermediate sequences are more likely to form disordered, branched structures. "We don't know if branching is good or bad," Wolynes said. "But it explains the weird shapes the experimentalists get in the test tube." Mutations that would encourage polyglutamine sequences to remain unfolded would raise the energy barrier to aggregation, they found. "What's ironic is that while Huntington's has been classified as a misfolding disease, it seems to happen because the protein, in the bad case of longer repeats, carries out an extra folding process that it wasn't supposed to be doing," Wolynes said. The team's ongoing study is now looking at how the complete huntingtin protein, which contains parts in addition to the polyglutamine repeats, aggregates.


News Article | November 10, 2016
Site: www.eurekalert.org

HOUSTON - (Nov. 10, 2016) - Rice University scientists have uncovered new details about how a repeating nucleotide sequence in the gene for a mutant protein may trigger Huntington's and other neurological diseases. Researchers at Rice's Center for Theoretical Biological Physics used computer models to analyze proteins suspected of misfolding and forming plaques in the brains of patients with neurological diseases. Their simulations confirmed experimental results by other labs that showed the length of repeating polyglutamine sequences contained in proteins is critical to the onset of disease. The study led by Rice bioscientist Peter Wolynes appears in the Journal of the American Chemical Society. Glutamine is the amino acid coded for by the genomic trinucleotide CAG. Repeating glutamines, called polyglutamines, are normal in huntingtin proteins, but when the DNA is copied incorrectly, the repeating sequence of glutamines can become too long. The result can be diseases like Huntington's or spinocerebellar ataxia. The number of repeats of glutamine can grow as the genetic code information is passed down through generations. That means a healthy parent whose huntingtin gene encodes proteins with 35 repeats may produce a child with 36 repeats. A person having the longer repeat is likely to develop Huntington's disease. Aggregation in Huntington's typically begins only when polyglutamine chains reach a critical length of 36 repeats. Studies have demonstrated that longer repeat chains can make the disease more severe and its onset earlier. The paper builds upon techniques used in an earlier study of amyloid beta proteins. That study was the lab's first attempt to model the energy landscape of amyloid aggregation, which has been implicated in Alzheimer's disease. This time, Wolynes and his team were interested in knowing how the varying length of repeats -- as few as 20 and as many as 50 -- influenced how aggregates form. "The final form of the protein detected in people who have Huntington's disease is a macroscopic aggregate made of many molecules, much like an ice crystal formed out of water has many molecules in it," Wolynes said. "This process needs to start somewhere, and that would be with a nucleus, the smallest-size cluster that will then be able to finish the process and grow to macroscopic size. "People knew that the length of the repeats is correlated with the severity of a disease, but we wanted to know why that matters to the critical nucleus size," he said. Experiments had demonstrated that sequences of 20 repeats or less remained unfolded - or "noodle-y," as Wolynes described them; they were able to clump into a nucleus only when four or more were gathered together in proximity. The researchers' simulations showed how sequences with 30 repeats or more are able to fold by themselves without partners into hairpin shapes, which are the building blocks for troublesome aggregates. Thus, for the longer sequences, even a single protein can begin the aggregation process, especially at high concentrations. The Rice team found that at intermediate lengths between 20 and 30 repeats, polyglutamine sequences can choose between straight or hairpin configurations. While longer and shorter sequences form aligned fiber bundles, simulations showed intermediate sequences are more likely to form disordered, branched structures. "We don't know if branching is good or bad," Wolynes said. "But it explains the weird shapes the experimentalists get in the test tube." Mutations that would encourage polyglutamine sequences to remain unfolded would raise the energy barrier to aggregation, they found. "What's ironic is that while Huntington's has been classified as a misfolding disease, it seems to happen because the protein, in the bad case of longer repeats, carries out an extra folding process that it wasn't supposed to be doing," Wolynes said. The team's ongoing study is now looking at how the complete huntingtin protein, which contains parts in addition to the polyglutamine repeats, aggregates. Rice graduate student Mingchen Chen is lead author of the paper. Co-authors are Rice postdoctoral researcher Min-Yeh Tsai and research scientist Weihua Zheng. Wolynes is the D.R. Bullard-Welch Foundation Professor of Science, a professor of chemistry, of biochemistry and cell biology, of physics and astronomy and of materials science and nanoengineering at Rice and a senior investigator of the NSF-funded Center for Theoretical Biological Physics at Rice. The National Institute of General Medical Sciences and the Ministry of Science and Technology, Taiwan, supported the research. The researchers used the NSF-supported DAVinCI supercomputer administered by Rice's Ken Kennedy Institute for Information Technology. This news release can be found online at http://news. A simulation shows 20-repeat polyglutamines aggregating. These low-repeat proteins require four or more in close proximity to form a nucleus around which aggregates can form. (Credit: Wolynes Research Lab/Rice University) A simulation shows 30-repeat polyglutamines aggregating. These higher-repeat proteins require only one to nucleate aggregates of the type implicated in Huntington's disease. (Credit: Wolynes Research Lab/Rice University) Rice University researchers built computer simulations of mutated proteins implicated in Huntington's and other neurological diseases to see how they develop. From left, Weihua Zheng, Min-Yeh Tsai, Peter Wolynes and Mingchen Chen. (Credit: Jeff Fitlow/Rice University) Simulations at Rice show how a repeating sequence in a mutant protein may trigger Huntington's and other neurological diseases. They confirmed the number of repeats is critical to how many proteins are needed to start an aggregate. Here, 20-and 30-repeat proteins take different forms to nucleate fibers. Graphic by Mingchen Chen

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