Curtis Gove Callan, Jr. - US grants

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9802484
Callan
A broad program of research centered on the foundations of string and quantum field theory is proposed. Much of the effort is devoted to the nonperturbative dynamics of strings and the applications of these advances to quantum gravity, black hole entropy and information loss problems. A second focus is to increase understanding of nonabelian gauge theory in order to examine physics beyond the standard model. Finally, research will be carried out using the tools of conformal field theory to problems in turbulence.
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Theoretical physics is the search for concise mathematical models of Nature. It has had great success in dealing with the inanimate world: we can now predict in quantitative detail what the most sensitive experiments will observe inside the nucleus and in the cosmos at large. By contrast, even as our ability to observe and measure improves dramatically, the phenomena of life remain largely unpredictable, even in their most qualitative aspects. In this project, a group of theoretical physicists will engage with students and postdoctoral scholars in an effort to close this gap; in short, to construct a theoretical physics of biological systems. The proponents have explored phenomena that span the tree of life: from metabolism in bacteria, through the determination of cell fate in embryonic development, to coding and computation of sensory information in brain. They have identified broad theoretical problems which cut across the traditional biological divisions of organism and system: Do living organisms operate near the limits set by the laws of physics as they gather and process information? Can we learn the detailed microscopic "model" of an organism, its "wiring diagram", from the finite set of observations we can make on how it behaves? How do organisms set the parameters that govern their function (i.e. how do they learn from experience)? These questions can all be given a mathematical form which guides a search for answers in terms of general principles, in the tradition of physics that will apply across disparate biological domains. The time is right to bring the beautiful phenomena of life under the powerful predictive umbrella of theoretical physics. Just as cosmology has progressed, in roughly one generation, from wild speculation to a precise framework for analyzing a rapidly expanding set of observations, the proponents believe that the intimate interaction between theory and experiment can lead to a new and deeper physics of biological systems. It is the creation of this scientific culture, where theory and experiment are equal partners in the exploration of life that is the fundamental intellectual merit of the project. It is not just the boundaries of academic disciplines, but our view of ourselves, which is at stake. A very important aspect of this project will be the training of a new generation of physicists for whom the development of a theoretical understanding of biological systems is a central part of their discipline. The graduate students and postdoctoral scholars who pass through the group will learn by example how to pursue that goal in a way consistent with the intellectual rigor and traditions of physics. They will eventually move on to faculty positions of their own, where they will transmit this attitude to new generations of students. More broadly, all project personnel are deeply engaged with new educational initiatives, addressing levels from the first year of college to advanced PhD students, which provide a more complete guide to the evolving, multidisciplinary intellectual landscape.

The participants in the project will assemble into subgroups to attack instances of these problems. The individual projects will have unusual scope: as an example, the question whether we can capture the complex statistics of biological behavior in a learnable mathematical model can be asked in very similar terms both of spiking retinal neurons, and of the antibody sequence repertoire of individual zebrafish. If the answer is yes and the models have similar mathematical structure, one will have learned something novel and deep about what makes evolved, living, systems different from the inanimate world. Since these questions can only be answered in the light of accurate data, the work will involve a close partnership with many experimental groups in fields ranging from bacteriology to human perceptual psychology. The product of these interactions will be the design of novel experiments and the creation of novel data analysis methods in order to address clearly formulated mathematical questions of broad significance.

This project is being jointly supported by the Physics of Living Systems program in the Division of Physics, the Cellular Cluster and the Systems and Synthetic Biology in the Division of Molecular and Cellular Biosciences, and the Neural Systems Cluster in the Division of Integrative Organismal Systems.

This collaborative research project, consisting of four institutions (Rice, Yale, UIUC and Princeton) aims to continue the Physics of Living Systems Student Research Network (PoLS SRN). This network has been in existence for four years and has had a dramatic impact on many graduate students, both in the US and abroad, working on the application of physical science techniques to living systems. These students now can participate in a global community that can help deal with the many complex issues involved in conducting research in such a new and inherently multidisciplinary field. These issues range from proper training, to gaining a broad perspective, to accessing technical expertise that may not be available at their home institution. In addition to the obvious broader impacts related to training of a research workforce, there are other broad impacts of this plan. Via the interaction of one of the PoLS nodes (Rice) with the biomedical community in Houston, students and faculty will be exposed to possible avenues whereby physics can contribute to human health issues. Funds to attract students from under-represented groups to network meetings will be available through the new funds administered by the newly proposed network coordinator. Also deas vetted by the PoLS SRN will be adapted to create student networks in other areas of science and engineering.

There is by now little disagreement with the general notion that concepts and methods from physics have been a critical contributor to the increased understanding of the living world, and that its importance will be growing as the scientific world moves toward an ever more quantitative and predictive form of biology. Thus, the physics community clearly needs to train a new generation of scientists who can lead this effort, scientists who have the right mix of physics/mathematics rigor and broad knowledge of living systems from molecular scales on up. The PoLS SRN aims at creating a community of graduate students who can collectively help themselves and their mentors accelerate and enhance this training process. This is being done by a mix of in-person and virtual modes of communication, and this proposal is a plan to continue and expand these efforts; it will reach more students, improve the social networking portals, and make use of the complementary research agendas of the different network nodes to provide broad technical expertise. Doing all of this, will boost the intellectual level of the entire research field and convince the best students that the Physics of Living Systems is truly the most exciting research frontier in 21st century science.

This project is being jointly supported by the Physics of Living Systems program in the Division of Physics, the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences, the Chemistry of Life Processes program in the Division of Chemistry, and the Cellular Dynamics and Function Program in the Division of Integrative Organismal Systems.

In this project the PIs will explore phenomena that span the tree of life: from metabolism in bacteria, through the determination of cell fate in embryonic development, to coding and computation of sensory information in the brain. They have identified broad theoretical problems which cut across the traditional biological divisions of organism and system: Do living organisms operate near the limits set by the laws of physics as they gather and process information? Can the detailed microscopic model of an organism, its wiring diagram be understood from the finite set of observations that can be made on how it behaves? How do organisms set the parameters that govern their function (i.e. how do they learn from experience)? These questions will be given a mathematical form, which will guide a search for answers in terms of general principles, in the tradition of physics, that will apply across disparate biological domains. The participants in the project will assemble into subgroups to attack instances of these problems. The individual projects will have unusual scope: as an example, the question whether the complex statistics of biological behavior can be captured in a learnable mathematical model will be asked in very similar terms both of spiking retinal neurons, and of the antibody sequence repertoire of individual zebrafish. These questions will be answered in the light of accurate data and the work will involve a close partnership with many experimental groups in fields ranging from bacteriology to human perceptual psychology. The product of these interactions will be the design of novel experiments and the creation of novel data analysis methods in order to address clearly formulated mathematical questions of broad significance. An important component of this project is the training of a new generation of physicists for whom the development of a theoretical understanding of biological systems is a central part of their discipline. The graduate students and postdoctoral scholars who pass through the group will learn by example how to pursue that goal in a way consistent with the intellectual rigor and traditions of physics.