Proposal to Establish a Neurophysics Group in the Department of Physics and Astronomy

Introduction

The Department of Physics and Astronomy at the UR has had a long standing interest in the field of Biological Physics, represented by the research program of Prof. Robert Knox, a recipient of the 1994 Biological Physics Prize of the American Physical Society. Tom Foster, Prof. of Imaging Sciences in the Medical Center, received his Ph.D. from the Department as student of Prof. Knox, and has held a joint appointment in Physics and Astronomy since 1992. However since Prof. Knox’s retirement in 1997 the Department has had no primary appointment in Biological Physics. At the same time, the field of Biological Physics has experienced a period of rapid growth, with most leading Physics departments seeking to establish programs in this area. The 1997 report of the Department’s Faculty Recruiting Strategy Committee (FRS) concluded that there was a consensus in the Department in favor of a new recruitment in the field of Biological Physics. However, due to the constraints on Department size under the University’s Renaissance Plan, and the need to maintain strengths and balance in traditional core areas, only one full time position was projected for an effort in Biological Physics.

In the Fall 1998, following the FRS report, a Committee to Explore the Future of Biological Physics was constituted. The Committee was charged with educating the Department about the field of Biological Physics, and in particular to consider the rationale for an appointment in Biological Physics within the Department of Physics and Astronomy, to investigate the environment for interdisciplinary activity in Biological Physics at the University, and to gauge the potential for the success and impact of such an appointment. In April 2001, after a series of University wide interviews, the Committee submitted its final report (attached as Appendix D), which was accepted by the Department. The report identified three areas of Biological Physics that seemed the best potential targets for recruitment: (i) probing biological systems at the single molecule scale, (ii) neuroscience, and (iii) bioinformatics. The report concluded that:

• Biological Physics is an exciting and rapidly growing sub-field of physics that is actively being pursued by a large fraction of the top physics departments in the country. • A very favorable environment currently exists at the University for a successful appointment by the Department in the field of Biological Physics. • The field of Biological Physics should be given high priority for the next available faculty recruitment.

In its effort to continue exploring the above fields of Biological Physics, the Department invited Karel Svoboda of Cold Spring Harbor Laboratory (CSHL) to give a Department colloquium in November 2003. Svoboda is an internationally recognized pioneer in the use of multi-photon microscopy to image neural activity in the living brain. Svoboda’s visit generated considerable excitement in the Department. Moreover Svoboda, in private discussions, made it clear that he intended ultimately to leave CSHL. Although CSHL offered excellent support in the life sciences, he viewed that his efforts would be limited by the absence of technical support in advanced optics and electronics. Svoboda indicated that he viewed Rochester favorably, but that he was looking to make a move to a university that would be making several coordinated hires in his area. In response to this visit, the Chair of Physics and Astronomy initiated discussions within the University to see if it might be possible to recruit Svoboda to UR. While there was strong support for this in Physics and Astronomy, as well as other Departments at the University, this effort ended when there appeared no way to coordinate the recruitment of the several positions that Svoboda indicated would be necessary for him to move. Svoboda subsequently left CSHL this past summer for the new Howard Hughes Medical Institute Campus at Janelia Farm.

The Department’s experience with Svoboda highlighted the following points: (1) High quality candidates exist that would be eminently fitting for an appointment in Physics and Astronomy, and that such candidates can be attracted to the University if we are allowed to make competitive offers, and (2) Our ability to attract the highest quality candidates will be greatly increased if we are able to make multiple faculty recruitments in a focused field. However such multiple recruitments necessitate the ability of the Department to grow modestly beyond its Renaissance Plan size.

In response to the College’s strategic planning exercise, the Department thus proposes a bolder initiative than that originally envisioned by our Committee to Explore Biological Physics. For the reasons detailed in the remainder of this proposal, the Department seeks College support to establish a new group in the field of neurophysics, i.e. physics as it relates to neuroscience (target (ii) of the 2001 Biological Physics Committee report). The conclusions of the following sections of this proposal may be summarized as follows:

• Neurophysics represents an opportunity for Physics and Astronomy to enter early into a promising and growing field of Biological Physics. • A group in neurophysics within the Department of Physics and Astronomy will leverage unique strengths at the University and help to establish an interdisciplinary program in brain research at UR that will be a world leader. • The Department should establish a group of three faculty in the field of neurophysics consisting of a mix of theory and experiment. One of these positions would be the Biological Physics position allocated according to the Department’s last long range strategic plan (FRS). Two new positions would be created by growth in Department size. The building of such a group should take place in consultation with leading physicists outside the University who are working in this area. Based on such consultations, different paths might develop: hiring one senior level researcher who will then provide direction and mentoring for recruiting the rest of the group; hiring simultaneously more than one senior researcher; hiring over a span of several years a group of outstanding junior level researchers.

Below we outline our arguments in support of this proposal. We start with a brief discussion of the historical and present day context for neuroscience as an area of Biological Physics. We then present the case why the University of Rochester is in a unique position to play a leading role in this area. In Appendix A we review several speakers who have visited the Department recently, and comment on them as models for the sort of people and programs we might seek to recruit. In Appendix B we include letters of support from related programs in the College. In Appendix C we give a list of links to people and programs mentioned in this proposal. In Appendix D we attach the 2001 report of the Department’s Committee to Explore the Future of Biological Physics. Neuroscience and Biological Physics

The discipline of physics has had a long history of major contributions to the field of neuroscience, from the experimental foundations of the field of electrophysiology during the time of Galvani, to the theoretical and experimental contributions of Helmholtz on axons, to the work of Cole on ionic transport through biological membranes and its influence on the subsequent work of Hodgkin and Huxley. More recently, new theoretical ideas and experimental techniques from physics have continued to make a significant impact on the field.

In theory, ideas from statistical physics have been applied in developing models of neural activity, information processing and computation in the brain. Perhaps the best known example of such theoretical work is the seminal work of John Hopfield (current president of the American Physical Society) on “spin glass” models of neural networks. Other leading theoretical physicists in this area include Bill Bialek (Princeton), Haim Sompolinsky (Hebrew University), Larry Abbott (Columbia), Terry Sejnowski (UCSD), Sebastian Seung (MIT) and Wulfram Gerstner (Lausanne). The role that theoretical physics has to play in modern neuroscience is evidenced by two recent workshops held at the Kavli Institute for Theoretical Physics at UC Santa Barbara: Dynamics of Neural Networks, July 23 - Dec. 22, 2001, and Understanding the Brain, July 19 – Oct. 1, 2004. Another symposium recently organized by the Institute for Complex Adaptive Matter was, Frontiers in Biological Physics III: Neural Biology, July 18-20, 2004, Aspen. The recognition by the neuroscience community that physics has an important role to play is evidenced by the creation in 1994 by the Sloan Foundation of five Centers for Theoretical Neurobiology (at Brandeis, Caltech, NYU, Salk Institute, and UCSF), whose goal was to “bring young theoreticians from the physical, mathematical and computer sciences into neurobiology.” In 2000, the Swartz Foundation joined in the funding of these centers. The Swartz Foundation, established to “explore the application of mathematical physics, computer science, systems analysis and behavioral psychology to neurobiology,” also supports centers in Computational Neuroscience at Cold Spring Harbor, Columbia, and UCSD.

Experimentally, imaging of individual neuronal synapses and networks by multi-photon spectroscopy and other advanced optical techniques have allowed unprecedented investigations of neuronal plasticity and metabolism. The Howard Hughes Medical Institute has just opened the Janelia Farm Research Campus with plans for up to 250 resident staff (including 24 group leaders and 20 fellows) to focus on problems in neuronal networking and imaging. It mission is: (i) “The identification of general principles that govern how information is processed by neuronal circuits,” and (ii) “The development of imaging technologies and computational methods for image analysis.” Experimentalist Harald Hess, a well known condensed matter physicist formerly at AT&T Bell Laboratories, is the Director of the Applied Physics and Instrumentation Group at Janelia Farm. Other experimental physicists, who will join Janelia Farm as Group Leaders, include Eric Betzig (formerly at Bell Laboratories) and Karel Svoboda (moving from Cold Spring Harbor). Charles Shank, former director of Lawrence Berkeley National Laboratory and presently Professor of Chemistry, Physics, Electrical Engineering and Computer Science at UC Berkeley, has been appointed as a Senior Fellow at Janelia Farm. Other leading experimental physicists working in neuroscience include David Kleinfeld (UCSD), David Tank (Princeton), and Winfried Denk (Heidelberg).

We believe that neurophysics represents an ideal direction for the Department of Physics and Astronomy in seeking to establish a program in Biological Physics. While the connection between physics and neuroscience is old and well established, and while many physicists have gone on to success obtaining faculty appointments in neurobiology related departments, neurophysics as a sub-field within a physics department has so far received less attention than other recently growing areas of Biological Physics (such as molecular motors, single molecule manipulations, investigations of physical properties of DNA, protein folding, etc.). However several such physics department based groups do exist, and more are being created. Established groups in physics departments include David Kleinfeld (experiment) at UCSD, Haim Sompolinsky (theory) at Hebrew University, and John Hertz (theory) at NORDITA. More recent hires into physics departments include Bill Bialek (theory) at Princeton, Rob de Ruyter (experiment) at Indiana U, Ralf Wessel (experiment) at Washington U, and Paul Tiesinga (theory) at U North Carolina Chapel Hill. Other well established condensed matter physicists are known to be making efforts to develop programs in this field (these include in theory: Daniel Fisher at Harvard, Mehran Kardar at MIT; in experiment: Josef Kas at Liepzig, Elisha Moses at Weizmann). We therefore believe that neurophysics represents an opportunity for Physics and Astronomy at Rochester to enter early into a promising and growing field.

The Broader UR Context for a Program in Neurophysics

A small research University like Rochester will increase its chances to achieve prominence in any particular field if it can leverage its strengths across multiple academic units. Biological Physics is by its very nature an interdisciplinary subject. As outlined below, we believe that a group in neurophysics within the Department of Physics and Astronomy will be an unparalleled match to the unique strengths at the University of Rochester. It thus will help to establish a broad interdisciplinary program in brain research at the University that will be a recognized leader in the field, while at the same time providing a new educational opportunity attractive to both undergraduate and graduate students. The programs with which we see a clear potential for strong interactions are now discussed below.

The Department of Brain and Cognitive Science (BCS) is, like Physics and Astronomy, one of the strongest departments in the College. It is one of the few such departments of its kind in the country, where the focus is on studying brain function and the fundamental processes underlying perception and cognition. Interaction between BCS and a neurophysics group would be natural and would leverage the strengths of each department. Teitel, a theorist in condensed matter physics, has started collaboration with Pouget in BCS to develop a program in neural computation. The current strategic planning report of BCS lists plasticity and neural computation as the two areas in which BCS is seeking to grow. Plasticity, which at the cellular level involves changes in neuronal connectivity and circuitry, and neural computation, which involves statistical models of information transmission and processing in the brain, are both areas with direct connections to neurophysiscs. The Chair of BCS, Elissa Newport, expressed considerable enthusiasm over the potential for such interactions (see attached letter in Appendix B).

Many of the new imaging techniques being developed to study activity in the brain involve advanced optical methods. Multi-photon microscopy is one clear example of a recent optical technique that has gone on to have dramatic impact in the field of neuroscience. The Institute of Optics, another unique UR department, can provide an outstanding human and technical resource for interactions to promote the development and application of this and newer optical methods applied to brain imaging. Robert Boyd, Parker Givens Professor of Optics, has already expressed his interest in this area (see attached email in Appendix B). Wayne Knox, Director of the Institute is similarly enthusiastic (see attached letter inAppendix B). The recently created Biomedical Engineering Department has “neuroengineering” and perceptual systems as one of its focus areas of research. David Pinto and others in this department offer natural possibilities for collaboration (see attached letter from Rick Waugh, Chair of BME). Facilities in the new Biomedical/Optics building may serve as an attractive resource and environment for interactions with a neurophysics group. The potential for collaboration with Computer Science exists through, for example, the sub-fields of machine learning or biological computation.

The Center for Visual Science is an existing interdisciplinary program currently involving BCS, BME, and the Departments of Neurobiology and Anatomy, Neurology, and Opthamology in the Medical Center. The Director of CVS, David Williams, expressed his view that there should be many close and exciting collaborations between a neurophysics group in the Physics Department and CVS members (such as Aslin, Bavelier, Merigan, Majewska, Weliky, and Williams) involved with optical imaging of neural activity (see attached letter in Appendix B).

The University Medical Center is another very attractive resource. That our Medical Center is only a short walk from the College (and not on the other side of town, or in a different town) is another advantage of Rochester that is lacking at many other universities. Neuroscience in the Medical Center is primarily housed in the Center for Aging and Developmental Biology (Howard Federoff, Director) and in the Department of Neurobiology and Anatomy (Gary Paige, Chair). Other relevant activity exists in the Department of Neurosurgery (for example the group of Maiken Nedergard). Both Federoff and Paige were interviewed by the Biological Physics Committee in 2001, and both were enthusiastic about possible collaborations with Physics. We recognize that there is a significant difference in culture and climate between the College and the Medical Center, so interactions may need to proceed carefully. However the Center for Visual Science and the Department of Biomedical Engineering may offer models and support for successful collaborations across Elmwood Avenue.

Most recently an effort has been underway to create the “Rochester Institute for Brain Sciences and Neuromedicine.” This is one of the four proposals put forward by the College’s Sciences Working Group Interim Report of 2/06. This is envisioned as a major interdisciplinary institute cutting across departments in the College such as BCS, Computer Science, Physics, Optics and BME, and in departments in the Medical Center such as Neurology, Neurosurgery, Neurobiology and Anatomy, and the Center for Aging and Developmental Biology. The Institute is intended to integrate brain related research throughout the University, in both basic science and clinical disciplines. The Institute will be formed around five centers, housed in a new facility: (i) Center for Translational Neuroscience, focusing on basic science relevant to understanding neurological disease, (ii) Center for Imaging Sciences, devoted to new imaging technologies for investigating brain function, (iii) Center for Bain Plasticity, Repair and Regeneration, dealing with the neural mechanisms of learning, memory, and cognition and how they are implemented at the cellular and molecular level with a focus on the potential for neural plasticity and regeneration, (iv) Center for Computation and the Brain, focusing on how the brain encodes, transmits, and processes information, and (v) Center for Best Practices and Neuromedicine Health Planning, dealing with regional neuromedicine disease management and cost effectiveness of care.

Clearly, if such a Brain Institute goes forward, it will have a major impact on all neuroscience related activity at the University. A neurophysics group in the Department of Physics and Astronomy could become an important component of such centers, while the resources of such an institute (the potential for new center related recruitments and presence of core facilities) would greatly increase the visibility and breadth of interactions of such a group. If, however, the Rochester Brain Institute should ultimately not be created, there remains enough firmly established activity within the College to ensure a broad base of strong interdisciplinary interactions.

While the opportunities and the enthusiasm for interdisciplinary interactions between a neurophysics group and other units of the University are thus manifest, we stress that we seek a neurophysics group in the Department of Physics and Astronomy that will have its own distinct profile. Physicists, educated and trained in physics departments and laboratories, have already made numerous seminal contributions to the field of neuroscience. It seems evident that new experimental methods and instrumentation, and new theoretical approaches and paradigms, yet to arise from physics research in possibly unrelated areas, will develop into new opportunities for investigating and thinking about problems in neuroscience. We therefore seek to recruit neurophysicists, dedicated to questions of basic science, that, while interacting with neuroscientists across a broad spectrum of activity, nevertheless wish to maintain strong ties to the physics community at large, have a home base in a physics department, and train students with a physics background. Such a group will enhance the true synergy that is the strength of interdisciplinary research.

Conclusion

Neurophysics is an exciting and growing area of Biological Physics with an established record of important contributions to the field of neuroscience. A group in neurophysics within the Department of Physics and Astronomy will enjoy excellent opportunities for interdisciplinary collaboration that will leverage the unique strengths of the University across multiple academic units. Creation of a group in neurophysics will allow the Department of Physics and Astronomy to rise to a position of national prominence in the area of Biological Physics, while contributing to the prominence of the University in the more general field of brain research. Creation of such a new group, representing a thrust into a new area of physics research, will be difficult to achieve within the confines of the existing Department size. We estimate a group of three full time faculty to be the minimum size necessary to create a cohesive effort that can span both experimental and theoretical activity and establish a major presence and visibility for the Department in this field. While starting such a new effort, however, care must be exercised to retain our existing strengths while balancing activities in other core areas of physics and astronomy. We therefore believe that growth is a necessary condition for the achievement of the program outlined in this proposal. We therefore propose a group of three full time faculty. One of these positions would be the Biological Physics position allocated according to the Department’s last long range strategic plan (FRS1). Two new positions would be created by investing College resources to allow for a net growth in Department size. Appendix A

Recent Visitors to the Department of Physics and Astronomy in Neurophysics

Since the Department’s acceptance of the Biological Physics Committee’s final report, numerous visitors have been brought to the Department to give colloquia and seminars in the field of neurophysics. These talks generally attracted a broad audience from a variety of departments and programs at the University including, Brain and Cognitive Science, Center for Visual Studies, Institute of Optics, and the Medical Center. A complete list of these visitors is attached at the end of this Appendix. Here we comment in greater detail on three of these visitors who can serve as models for the sort of candidates and programs we might try to recruit.

William Bialek (Princeton)

Bialek received his Ph.D. in Biophysics from UC Berkeley in 1983. After postdoctoral positions at Groningen and the Institute for Theoretical Physics in Santa Barbara, he was an Assistant Professor of Physics and Biophysics at Berkeley from 1989-1991. From 1990-2001 he was a Senior Research Scientist and then an Institute Fellow at NEC Research Laboratories. In 2001, the same year he visited Rochester, he moved to the Physics Department at Princeton where he is currently Wheeler/Battelle Professor of Physics, a Member of the Institute for Integrative Genomics and an Associated Faculty in the Department of Molecular Biology and the Programs in Applied and Computational Mathematics and Neuroscience. He has been a lecturer and co- director of a Summer Course on Computational Neuroscience at the Woods Hole Marine Biology Laboratory since 1991, a visiting faculty at the Sloan-Swartz Center for Theoretical Neurobiology at USCF since 1994, and a consultant at the Center for Theoretical Neuroscience at Columbia since 2005. He is currently on the advisory boards of the Kavli Institute for Theoretical Physics, Santa Barbara (since 2005), the Max Planck Institute for Dynamics and Self–Organization (since 2004), and the Scuola Internazionale Superiore di Studi Avanzati (since 2001). He has served on the National Research Council Board on Physics and Astronomy (1999-2002), and on the Editorial Boards of Annals of Physics (since 2002), Journal of Statistical Physics (1997-99), and Neural Computation (since 1993). Bialek’s area of interest is in codes, computation and learning in the nervous system and its connections to statistical physics and information theory. More generally he is interested in issues relating to noise and the physical limits it places on biological functions, and the notion of biological information from the molecular and cellular scales to perception and learning in the brain. He is a co-author of the seminal book, Spikes: Exploring the Neural Code.

Bialek was invited to Rochester in November 2001 to give the Eighteenth Annual David L. Dexter Lecture in the Department of Physics and Astronomy. His talk was very well received in the physics department, and an informal poll by Dave Williams of CVS (Center for Visual Studies) members attending the talk indicated that Bialek was the sort of person who could fit well with CVS’s mission. During his visit Bialek mentioned his view that the physics of neural systems was somewhat less on the radar screen of departments seeking to build programs in biological physics as compared to other “hot” topics such as single molecule fluorescence spectroscopy or optical tweezers. Yet he noted that Princeton physics had just (in 2001) hired two faculty in this area – himself (from NEC) and David Tank (from Bell Labs).

Karel Svoboda (formerly at Cold Spring Harbor, now at HHMI Janelia Farm)

Svoboda received his B.A. in Physics from Cornell and his Ph.D. in Biophysics from Harvard in 1994. After a postdoctoral position at AT&T Bell Labs he joined Cold Spring Harbor in 2000 as a Howard Hughes Medical Institute Investigator. In the summer of 2006, Svoboda moved to become a group leader at the new Howard Hughes Medical Institute Research Campus at Janelia Farm. Svoboda’s research involves the use of novel imaging methods to study plasticity in the developing and adult neocortex. He is a pioneer in the use of 2-photon scanning laser microscopy to study the changes in individual synapses, neurons and networks, in response to experience driven learning in living mice over extended periods of time (up to one month). One of his papers, Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex, Nature 2002, has 270 citations. Another paper, Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo, Nature 2000, has 230 citations. His most cited works, both in Science 1999, are, Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation, with 473 citations, and Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity, with 454 citations.

Svoboda’s visit to Rochester in November 2003, to give a colloquium in the Department of Physics and Astronomy, generated considerable excitement. Privately, he discussed his future career plans, indicating that he did not wish to remain at Cold Spring Harbor Laboratory (CSHL) forever. Although CSHL offered excellent support in the life sciences, he viewed that his efforts would be limited by the absence of technical support in advanced optics and electronics. In casual conversation he indicated that Rochester was the sort of University he could see himself winding up at after some years, and that he was impressed with plans for the new Biomedical/Optics Building. He said that when he decided to leave CSHL, he would be looking to move somewhere that would be hiring a group of two or three faculty on the same time scale. In response to this positive feedback, the Chair of Physics and Astronomy initiated discussions within the University to see if it might be possible to recruit Svoboda to UR. While there was strong support for this in Physics and Astronomy, as well as other Departments at the University, this effort ended when there appeared no way to coordinate the recruitment of the several positions that Svoboda indicated would be necessary for him to move.

Harshad Vishwasrao (Columbia)

Unlike Bialek and Svoboda, Vishwasrao is a junior researcher. Vishwasrao received his Ph.D. in Physics from Cornell in 2004, under the supervision of Prof. Watt Webb. Webb is the “father” of multi-photon spectroscopy as applied to imaging in biological systems. His earlier Ph.D. students in this field include David Tank (Princeton), Winfried Denk (Heidelberg), and more recently Ed Brown (UR Biomedical Engineering). Vishwasrao’s thesis involved the use of 2-photon fluorescence microscopy to quantitatively study metabolism in astrocytes and neurons in brain tissue slices. His most cited paper is Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis, in Science 2004, which has received 79 citations. Vishwasrao is currently a postdoctoral associate in the Columbia University Center for Neurobiology and Behavior.

Vishwasrao visited the Department in March 2006 to give a Biological Physics Seminar. Vishwasrao made a very strong positive impression on members of the Department, from a wide variety of physics sub-fields, who attended his talk. Many commented that he appeared to be a rising “star.” Vishwasrao has a strong connection to Rochester. Karl Kasischke (M.D.), who collaborated with Vishwasrao when Kasischke was a postdoc in Webb’s lab, is currently a Research Assistant Professor in the Department of Neurosurgery and in the Center for Aging and Developmental Biology at the UR. Vishwasrao indicated that he would probably not be looking for a faculty position for another several years.

List of Recent Talks in Neurophysics in the Department of Physics and Astronomy

Joint BCS/Biological Physics Seminar 12/3/01 Rob de Ruyter van Steveninck NEC Research Institute How to Estimate Self Motion, and How the Blowfly Does It (de Ruyter has since moved to the physics department at Indiana University)

Physics and Astronomy Colloquium 11/7/01 Eighteenth Annual David L. Dexter Lecture Prof. William Bialek Physics Department, Princeton University Pushing the Physical Limits: Optimization in Neural Coding and Computation

Physics and Astronomy Colloquium 2/12/03 Prof. Laurence Abbott Volen Center for Complex Systems and Dept. of Biology, Brandeis University Timing-Dependent Mechanisms for Shaping and Maintaining Neural Circuits (Abbott has since moved to the Center for Neurobiology and Behavior at Columbia)

Physics and Astronomy Colloquium 11/19/03 Prof. Karel Svoboda Cold Spring Harbor Laboratory Using Light to Study the Brain at the Level of Molecules, Synapses, and Neural Circuits (Svoboda is moving to the Howard Hughes Medical Institute, Janelia Farm Research Campus)

Joint Physics and Optics Colloquium 3/17/04 Prof. Mark Raizen Dept. of Physics, Univ. of Texas, Austin New Frontiers in Controlling the Motion of Matter with Light: from Single Atoms to Neurons

Biological Physics Seminar 3/27/06 Dr. Harshad Vishwasrao Center for Neurobiology and Behavior, Howard Hughes Medical Institute & Columbia University Two-Photon Fluorescence Microscopy and Spectroscopy of Neuro-Metabolic Dynamics

Appendix B – Letters of Support from other Programs within the College

Email from Elissa Newport, Chair of the Department of Brain and Cognitive Science

attached

Letter from Wayne Knox, Director of the Institute of Optics

attached

Email from David Williams, Director of the Center for Visual Science

attached

Email from Richard Waugh, Chair of the Department of Biomedical Engineering

attached

Email from Robert Boyd, Parker Givens Professor of Optics

attached

X-Original-To: [email protected] Delivered-To: [email protected] Date: Wed, 11 Oct 2006 11:08:38 -0400 To: [email protected] From: Elissa Newport Subject: Neurophysics and BCS Cc: [email protected]

Dear Steve,

I'm writing, as chair of Brain & Cognitive Sciences, to express my enthusiastic support for the direction your department is considering in adding a neurophysics group. As you know, there have already been exciting interactions beginning between Physics and BCS. Since your Bridging Fellowship to BCS and Alex Pouget's Bridging Fellowship to Physics, there has begun to be a very exciting research group building around the topic of computational neuroscience that has already attracted some of our strongest applicants for graduate and postdoctoral training from backgrounds in physics and in neuroscience. The students in our department that are currently working with Alex and with you are, I'm sure, only the tip of what we can expect to see in outstanding talent that a group in this cutting edge field can attract. As you know, BCS has a larger group of faculty working on computational approaches to perception, cognition, learning and the brain that will interface with a neurophysics group as well.

More generally, because of the strengths of your department and ours in many surrounding fields, as well as the strength in CVS, BME, CS, ECE, and the Neuroscience cluster in the Medical Center, I am confident that you can attract remarkable faculty members to this field. Such a group will be an important component in our interdisciplinary community and can help to move forward a university-wide Institute for Brain Sciences. This is therefore an ideal area in which to add a new group. You can be assured that our strengths in these fields in other parts of the university will assist your department in attracting the very best scientists to Rochester.

I look forward to continuing to work with you - please let me know if there is anything else that BCS or I can do to support this exciting initiative.

Best,

Elissa

Elissa L. Newport Chair, Department of Brain & Cognitive Sciences George Eastman Professor

[email protected]____

Wayne H. Knox Professor of Optics and Physics Senior Scientist at the Laboratory for Laser Energetics Director of The Institute of Optics Wilmot 113 University of Rochester Rochester, NY 14627-0186 585-273-5520 585-273-1072 (fax)

October 6, 2006 Arie Bodek Chair, Physics and Astronomy Department Re: Proposal for Neurophysics group

Dear Arie: I write to express my strong support for a Neurophysics group in the Department of Physics and Astronomy, as outlined in your proposal. I am aware of the Jenalia Farms initiative, as my former research Director from Bell Labs Charles V. Shank, who was more recently the Director of Lawrence Berkeley Labs, is now setting up a research group there. In addition, I note that I have collaborated [1] with both Winfried Denk and Karel Svoboda in the first application of compact solid-state femtosecond modelocked lasers to the study of 3D imaging of neurons by two-photon excited fluorescence in living rat brain tissue in 1996. Karel is now heading to Jenalia Farms. Therefore, I am personally interested in this line of research. But moreover, I think that this will be highly synergistic with a focus area that we have identified in our collaboration with the Biomedical Engineering Department, that being biomedical optics, and I think that Neurophysics is a great opportunity for the University. As we are getting ready to expand into the new 101,000 square foot Goergen BMEO building, it is a great time to be recruiting new faculty in closely related areas. Many new joint projects can be envisioned involving our current collaborators in CVS, BME, Ophthalmology, BCS, etc. Sincerely yours

Wayne H. Knox

[1] K. Svoboda, W. Denk, W.H. Knox and S. Tsuda, “Two-Photon-Excitation Scanning Microscopy of Living neurons with a Saturable Bragg Reflector Modelocked diode-Pumped Cr:LiSAF Laser”, Optics Letters 21, 1411 (1996). From: Rick Waugh <[email protected]> Date: October 6, 2006 8:58:29 AM EDT To: N Bigelow <[email protected]> Subject: Re: Physics Initiative

Nick,

My first appointment ended early and this seems like just enough time to look over your proposal. In general I think it is a great idea. You should be aware of two other individuals who could serve as resources/contacts as you move forward. David Pinto in BME/NBA is working on applications of dynamical systems analysis to understand somato-sensory networks. His work is both theoretical and experimental. Ania Majewski shares the lab with Ed Brown and is using two-photon fluorescence to study neuroplasticity. Also working on related topics are Kevin Davis, who is sorting out auditory processing in the brain stem using experimental approaches and signal processing analysis. Finally, Greg Gdowski works on systems modeling of the control of head and neck movements. Thus, I think that your proposed initiatives would have a lot of tie-ins with what BME has tried to build in the application of physical sciences to neural function.

BME can also help in bridging the cultural differences between the College and SMD you mention in your report. You should not be daunted by these. There is too much of value to your program to let this be any kind of barrier to collaborating with SMD investigators. You do not mention ties to the Brain imaging center, but this could also be a valuable resource for you depending on who you consider for faculty positions.

Finally, I would be cautious about hiring theoreticians who are not very well-connected to experiment. There is a lot going on in abstract analysis of how the brain functions, but my impression is that this tends to be a field unto itself, without viable contacts to experimentalists or to the true physics underlying brain function. Dave Pinto can give a more expert opinion about this.

Overall I think it is an excellent idea and well tuned to existing strengths and opportunities at Rochester.

Rick

X-Original-To: [email protected] Delivered-To: [email protected] Date: Sat, 7 Oct 2006 04:33:00 -0400 To: Stephen Teitel From: David Williams Subject: Re: proposal from physics Cc: [email protected]

Dear Steve,

I think that your proposal represents a very exciting direction for UR. Many members of the Center for Visual Science would interact closely with the neurophysics group you envision. In particular, there would be especially close links in the area of optical imaging of neural activity. Dick Aslin, Daphne Bavelier, Bill Merigan, Ania Majewska, Mike Weliky, and I are examples of such CVS faculty. Maiken Nedergard's laboratory in SMD may also tie in as they are engaged in work on two photon, functional imaging of astrocytes among other things. My laboratory is moving rapidly into the use of, for example, fluorescent compounds attached to AAV vectors to selectively label individual retinal neurons. We are especially interested in new functional biomarkers that will allow us to monitor the activity of retinal neurons in vivo. I would think that Aslin's Rochester Center for Brain Imaging could tie in with your initiative, if your group developed a focus on the physics of fMRI. All of these activities would find great synergy with a group in physics that had expertise in the development of novel methods of interrogating neurons and neuronal circuitry. I can well imagine your new group being a key component of the Rochester Institute for Brain Sciences and Neurmedicine, especially in the area of imaging. Please let me know how your discussion goes on Wednesday and whether I can be of additional help. I am having discussions with various people both in the College and SMD about the neural imaging thrust of the proposed Brain Institute and would welcome the chance to help physics develop their plans in the context of the developing strengths in related areas elsewhere in the College and SMD.

Best Wishes,

David

X-Original-To: [email protected] Delivered-To: [email protected] Date: Sat, 23 Sep 2006 13:55:24 -0400 To: Stephen Teitel , "Nicholas P. Bigelow" From: "Robert W. Boyd" Subject: Re: neuroscience proposal Cc: [email protected] X-Brightmail-Tracker: AAAAAA== X-Brightmail-scanned: yes

Dear Steve and Nick

I am writing to let you know that I am interested in this topic area. I have a collaboration under way with a vision person (Vengu for short) in the area of measuring the human visual response for quantum states of light. (Past studies have used light pulses containing a statistical distribution of photon numbers.) This work could fit in with the general structure of this program.

If and when you need specific input from me, please let me know.

Bob

Appendix C - References to People and Programs Cited in the Proposal

People (by no means a complete list of physicists working in the field)

Theorists:

Larry Abbott Professor Neurobiology and Behavior, Columbia PhD in Physics http://www.cumc.columbia.edu/dept/neurobeh/Abbott.html

Bill Bialek Professor Physics, Princeton PnD 1983 in Biophysics, UC Berkeley http://www.physics.princeton.edu/www/jh/research/bialek_william.html

Daniel Fisher Professor Physics, Harvard PhD 1979 in Physics, Harvard University http://www.physics.harvard.edu/people/facpages/fisher.html

Wulfram Gerstner Director Laboratory of Computational Neuroscience, Ecole Polytechnique Federale de Lausanne PhD 1993 in Theoretical Biophysics, Technical University of Munich http://diwww.epfl.ch/~gerstner/

John Hertz Professor Physics NORDITA, Copenhagen PhD 1970 in Physics, University of Pennsylvania http://www.nordita.dk/~hertz/

John Hopfield Professor Molecular Biology (and Physics), Princeton PhD 1958 in Physics, Cornell http://www.molbio.princeton.edu/research_facultymember.php?id=41 http://genomics.princeton.edu/hopfield/Biography.html

Mehran Kardar Professor Physics, MIT PhD in Physics http://www.mit.edu/~kardar/

Terry Sejnowski Professor Computational Neurobiology, Salk Institute PhD in Physics, Princeton http://www.salk.edu/faculty/faculty/details.php?id=48

Sebastian Seung Professor Brain and Congitive Science, MIT PhD in Physics, Harvard http://hebb.mit.edu/people/index.html Haim Sompolinsky Professor Physics and Interdisciplinary Center for Neural Computation, Hebrew University PhD in Physics http://neurophysics.huji.ac.il/~haim/

Paul Tiesinga Assist Prof Physics, U North Carolina at Chapel Hill PhD 1996 in Physics, Utrecht University http://neuro.physics.unc.edu/

Experimentalists:

Eric Betzig Group Leader, HHMI Janelia Farm PhD in Applied and Engineering Physics, Cornell http://www.hhmi.org/research/groupleaders/betzig_bio.html

Winfried Denk Director Dept of Biomedical Optics, Max Planck Institute for Medical Research, Heidelberg Professor Physics, University of Heidelberg PhD in Physics 1990, Cornell http://wbmo.mpimf-heidelberg.mpg.de/winfriedDenk/index.html

Rob de Ruyter van Steveninck Professor Physics and Progarm in Neural Science, Indiana University PhD. 1986, U of Groningen http://www.physics.indiana.edu/faculty/DeRuyter.shtml

Harald Hess Director Applied Physics and Instrumentation, HHMI Janelia Farm PhD in Physics, Princeton http://www.hhmi.org/janelia/hess.html

Josef Kas Professor of Physics, U of Leipzig and Director Instit. of Soft Matter Physics Dr. rer. nt. 1993 in Physics, Technical University of Munich http://www.uni-leipzig.de/~pwm/kas/jkas/jkcv.html

David Kleinfeld Professor Physics and Program in Neuroscience, UC San Diego PhD 1984 in Physics, UC San Diego http://physics.ucsd.edu/neurophysics/kleinfeldcv.html

Elisha Moses Professor Physics of Complex Systems, Weizmann Institute PhD ~1987 Physics, Weizmann Institute http://www.weizmann.ac.il/home/fnmoses/home.html

Charles Shank Senior Fellow, HHMI Janelia Farm PhD 1969 in Electrical Engineering, UC Berkeley Director Lawrence Berkeley Laboratory, 1989-2004 http://www.hhmi.org/janelia/shank.html

Karel Svoboda Group Leader, HHMI Janelia Farm PhD 1994 in Biophysics, Harvard http://www.hhmi.org/research/groupleaders/svoboda_bio.html

David Tank Professor Molecular Biology (and Physics), Princeton PhD 1983 in Physics, Cornell http://www.molbio.princeton.edu/research_facultymember.php?id=43

Ralf Wessel Professor Physics, Washington University PhD 1992 in Physics, Cambridge http://physmail.wustl.edu/Fac/Wessel.html

Centers and Programs

Sloan-Swartz Centers for Theoretical Neurobiology http://www.sloan.org/programs/scitech_supresearch.shtml Brandeis http://sloan.caltech.edu/ Caltech http://sloan.caltech.edu/ NYU http://www.cns.nyu.edu/ Salk Institute http://www.sloan-swartz.salk.edu/home.htm UC San Francisco http://www.sloan.ucsf.edu/sloan/

Swartz Centers for Computational Neuroscience http://www.theswartzfoundation.org/research.asp Cold Spring Harbor http://www.cshl.edu/public/releases/swartz.html Columbia http://www.neurotheory.columbia.edu/index.html UC San Diego http://www.sccn.ucsd.edu/

Howard Hughes Medical Institute Janelia Farm Campus http://www.hhmi.org/janelia/

Kavli Institute for Theoretical Physics, Santa Barbara Dynamics of Neural Networks, July 23 to December 23, 2001 http://www.kitp.ucsb.edu/activities/auto2/?id=3 Understanding the Brain, July 19 to October 1, 2004 http://www.kitp.ucsb.edu/activities/auto2/?id=287

Institute for Complex Adaptive Matter (ICAM) Symposium: Frontiers in Biological Physics III: Neural Biology, July 18-20, 2004, Aspen http://icam.lanl.gov/aspen/frontiers.html

Appendix D

Report of the Committee to Explore the Future of Biological Physics within the Department of Physics and Astronomy

attached and available at: http://www.pas.rochester.edu/~stte/bio/

Report of the Committee to Explore the Future of Biological Physics in the Department of Physics and Astronomy

Nicholas Bigelow Tom Foster Yongli Gao Bob Knox Adrian Melissinos Yonathan Shapir Steve Teitel

submitted April 24, 2001

I - Introduction

In the Fall of 1998 the Chair appointed a committee to advise the Department on Biological Physics. The charge to the committee is to be found in Appendix A. We also note that the 1997 report of Faculty Recruiting Strategy (FRS) concluded that there was "a rather broad consensus within the Department to add a position in Biological Physics".

The committee considered in particular, the following: i) The rationale for an appointment in Biological Physics in a department of Physics and Astronomy ii) The environment at the University of Rochester in support of activity in Biological Physics iii) The funding opportunities in Biological Physics iv) The impact of a position in Biological Physics upon the Department

To address these questions the committee invited several distinguished researchers in the field of Biological Physics to visit campus as colloquium speakers, and to consult with the committee (see Appendix B for a list of these visitors). The committee further carried out an extensive set of meetings with faculty at the University in other departments, both in the College and in the Medical Center, whose research activities have a strong overlap with Biological Physics (see Appendix C for a list of faculty consulted).

As a result of these meetings the committee concludes that:

Biological Physics is an exciting and rapidly growing sub-field of physics that is actively being pursued by a large fraction of the top physics departments in the country. that:

A very favorable environment currently exists at the University for a successful appointment by the Department in the field of Biological Physics. and therefore recommends that:

The field of Biological Physics be given high priority for the next available faculty recruitment.

The remainder of this report is organized as follows: In section II we outline some of the recent scientific developments in the field of Biological Physics that have made it a clear growth area for top physics departments worldwide. In section III we summarize ongoing research activities

2 at the University that serve as natural intellectual support, and potential research collaboration, for an appointment in Biological Physics. In section IV we discuss the prospects for external funding. In section V we present our recommendations for a recruitment in Biological Physics.

II - Recent Developments in Biological Physics

The last decade has seen an explosion of growth in the application of the methods and ideas of physics to systems of biological interest. Many leading universities -- Princeton, Cornell, Chicago, Stanford, Rockefeller, Caltech, Berkeley -- are aggressively seeking to establish major cross-disciplinary initiatives in this direction [1]. Physics Nobel Laureate, and UR Trustee, Steven Chu (B.S. physics/math '70) has been one of the leaders of this effort at Stanford.

A brief list (obtained by personal contacts, scanning ads in Physics Today, online sources) of other physics departments that have recently recruited, or are presently recruiting, in the area of biological physics include: Ohio State, U. Minnesota, U Illinois-UC, U. Pennsylvania, Purdue, Syracuse, Northeastern, U. Texas at Austin, U. Arizona, Dartmouth, Michigan State U, Rice, Vanderbuilt, Dartmouth, U. Guelph, U. Missouri-Columbia, U. British Columbia. In preparing its report in 1997, the FRS contacted the chairs of 14 representative physics departments and reported, "Almost all of the departments contacted are interested in starting or expanding programs in Biophysics." After attending this year's Meeting of the Physics Chairs of Midwestern Universities, Bodek reported a similar wide spread interest in establishing programs in Biological Physics among the represented departments.

Not only has physics shown an increased interest in biology, but there has correspondingly been an increasing realization in the biomedical community, and at the federal funding agencies [2,3,4], of the expanded role that physicists can play in biological/medical research. To quote from former director of NIH Harold Varmus' address to the Centennial meeting of the American Physical Society in March 1999, "... the NIH can wage an effective war on disease only if we ... harness the energies of many disciplines, not just biology and medicine. These allied disciplines range from mathematics, engineering, and computer sciences to sociology, anthropology, and behavioral sciences. But the weight of historical evidence and the prospects for the future place physics and chemistry most prominently among them.... I would argue that we need to show our appreciation of physics-based technology by investing NIH funds more aggressively in its development." [3]

This recent growth of physics into biology is due primarily to two complementary developments:

(i) Biological mechanisms are increasingly being studied at the molecular level; one seeks to identify the molecular structures responsible for key reactions, and then to relate their properties to the behavior of the larger biological structure. Traditionally, this is an area that has been advanced by the procedures and technology arising in experimental physics, such as x-ray crystallography and magnetic resonance spectroscopy.

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In recent years, new physical techniques have been developed that allow for the direct observation and manipulation of individual macromolecules and complexes of large molecules. The ability to study individual molecules (in contrast to previous methods that only measure averages of statistical ensembles) is particularly important for biomolecular applications where heterogeneous environments are common and where molecules may be found in different configurations or folded states. Single molecule techniques further allow for the direct study of time dependent processes without the need to synchronize the behavior of a large ensemble. Stochastic fluctuations, which may play an important role in the function of particular biomolecules, can also be directly studied. Finally, the manipulation of single molecules offers the promise of constructing artificial molecular machines.

Examples of such single molecule techniques include: laser induced fluorescence spectroscopy, in which fluorescent probes (often a small dye molecule) are covalently bonded to specific sites of larger biomolecules. Analysis of location, polarization, time dependence and spectral content of the emitted photons provides structural and dynamical information about the molecule's diffusion, conformational state, and biological activity; laser traps (also known as optical tweezers) in which tightly focused laser beams are used to trap tiny dielectric plastic beads which have been linked to biomolecules of interest. By manipulating the laser beams to pull or push on the beads, one can make precision measurements of the mechanical properties of the biomolecules. Optical tweezers have been applied to studies of enzyme-DNA interactions, molecular motors, and protein folding; scanning probe techniques, in which one probes the nanometer scale interactions between a surface of interest, and a sharp tip that is scanned across it. Scanning tunneling microscopy (STM) has been used to make direct real space images of biomolecular conformations, as well as to manipulate molecules to create supramolecular assemblies. Atomic force microscopy (AFM) has been used to measure mechanical properties of biomolecular forces to pico-newton sensitivity. Examples of current work in the area of single molecule techniques can be found in recent special issues of Science [5] and of Chemical Physics [6].

Leading groups in this area include Chu [7], Block [8] and Moerner [9] (Stanford), Quake (Caltech) [10], Bensimon (Ecole Normal) [11], Weiss (LBL) [12], Libchaber (Rockefeller) [13].

Also in the realm of new physical techniques in the service of Biological Physics is the use of artificially fabricated micro- and nano-scale environments for studying biological systems. Groups in this area include Craighead (Cornell) [14] and Austin (Princeton) [15].

(ii) There is an increasing appreciation of the fundamental role that statistical concepts and complex networked interactions play in biological systems, and in the problem of analyzing large and complex data sets to infer these underlying interactions. Statistical and condensed matter physics has experienced an increasing migration into biological areas related to such issues.

Problems in this category include understanding the neural networks by which the brain and nervous systems of higher organisms process and store information; the functioning of

4 membranes and protein-membrane interactions; understanding the protein and enzyme networks that control cell functioning; protein folding and the relation between structure and biological function ("proteomics"); the relation between gene sequence and function ("genomics").

The latter topic, often referred to as "bioinformatics", has been greatly stimulated by new DNA microarray technologies which allow the simultaneous "measurement of the extent to which different genes are read to form RNA (and subsequently protein) in different tissues and under different environmental conditions" [3]. Such microarray experiments have resulted in a glut of data, the quantitative understanding of which poses new theoretical challenges for biologists.

The generic and conceptual statistical issues arising in understanding such biological networks, such as optimization, partitioning, pattern recognition and data clustering, share many common themes with ideas concerning complex and critical behavior in statistical physics. The growing interest within the statistical and condensed matter physics community in such topics is witnessed by the fact that two of the premier national conference centers of physics have recently hosted workshops in this area: "Genetic and Biochemical Networks" Jan. 23-29, 2000 at the Aspen Center for Physics, and "Statistical Physics and Biological Information" Jan. 16 - June 15, 2001 [16], and "Dynamics of Neural Networks" July 23 - Dec. 22, 2001 [17], both at the Institute for Theoretical Physics, UCSB.

Leading experimental groups in this area include Leibler (Princeton) [18], Libchaber (Rockefeller) [13], Kas (Texas-Austin) [19], Kleinfeld (UCSD) [20]; in theory they include Shakhnovich (Harvard) [21], Onuchic (UCSD) [22], Hwa (UCSD) [23], Siggia (Rockefeller) [24], Maritan (SISSA).

III - Related Research at the University of Rochester

To explore the local activity at the University that could act in support of a position in Biological Physics, the committee conducted over the past year an extensive series of meetings with faculty from other departments, both on the River Campus and at the Medical Center. The committee was greatly impressed with both the breadth of this activity, and with the general enthusiasm that was displayed at the prospect of an appointment in Biological Physics in the Department of Physics and Astronomy. Below we summarize some of this existing activity, as well as the impressions we gathered from our meetings.

A - River Campus

Chemistry Department

In many respects chemistry provides a natural bridge between physics and biology. Physical chemists have scientific and analytical training similar to that of physicists, yet they are accustomed to dealing with the more complex molecular problems such as are encountered in biology. At the UR, several faculty have direct research interests in topics relating to Biological Physics. Turner studies RNA folding and prediction of RNA secondary structures, with

5 applications to questions involving bioinformatics (he is a co-PI on the University's MD/PhD training grant, and has other close collaborations with the Medical Center). Krugh and Bren conduct NMR studies of DNA and RNA structure, and metallo-protein folding, respectively. Miller's group is involved with the design of small molecules capable of specific binding to selected protein, RNA, and DNA sequences. Krauss is a new experimentalist studying the optical properties of nanometer scale materials (nanocrystals, nanotubes), including their potential for use as markers for imaging in biological systems. Mukamel is well known theorist working on ultrafast dynamics and relaxation processes in large molecules and biological complexes. Dellago is a young theorist carrying out simulations of dynamics in complex systems, such as chemical reactions in solution and conformational changes in biomolecules. Krauss and Dellago both have their PhD's in physics. Turner, Krugh, Bren and Miller are members of the Medical Center's cluster on Biophysics and Structural Biology (see below). In our meeting, Turner, Krugh and Bren spoke positively of their interactions with the Medical Center and felt that the climate at Rochester was conducive to interdisciplinary interactions. Mukamel expressed his view that a program in single molecule methods would be a natural choice for a Biological Physics position at the UR.

Institute of Optics

The institute of Optics has made two recent appointments in areas relevant to Biological Physics. Novotny is building a laboratory to do near-field microscopy of nanoscale materials, including biomolecules. Berger (PhD in physics) is building a laboratory to use Raman spectroscopy as a method for analyzing the content of tissue, blood samples, and living subjects. Novotny was very enthusiastic about potential collaboration should a position in Biological Physics be in the area of single molecule methods. Both Berger and Novotny are examples of the sort of small scale single-investigator type programs that a position in Biological Physics is likely to be; both seem to have gotten off to very promising starts at the University, receiving federal funding and easily finding contacts for potential interdisciplinary collaborations. The new director of the Institute of Optics, Wayne Knox, is reportedly interested in expanding the number of appointments in biomedical optics within the Institute.

Center for Visual Sciences

Committee members met with David Williams, Director of the Center for Visual Science and Prof. of Brain and Cognitive Sciences, and Allyn Chair of Medical Optics. The center is a broad interdisciplinary effort involving the departments of Brain and Cognitive Sciences and Computer Science on the River Campus, and the departments of Neurobiology and Anatomy, Neurology and Ophthalmology in the Medical Center. Roughly half of its 26 members are in River Campus departments, and half are at the Medical Center. The center serves as a good example of effective collaboration across Elmwood avenue. The center has umbrella training and core grants from NIH which help to support seven support staff members. Research at the center ranges from development of the visual system to the interaction between visual perception and memory. Williams own area of research involves optical techniques to study the structure of the eye and the optical and neural limits of human vision. Williams was enthusiastic about interactions with the Department of Physics and Astronomy, and mentioned as possible

6 areas of overlap the general field of neuroscience, the physics of NMR applications in biological tissue, and adaptive optics.

Other Departments

The committee also met with Biology chair Angerer. While generally positive, Angerer did not mention any specific areas of interaction that seemed promising to him. However Orr and Huelsenbeck's work in evolutionary biology has potential overlap with the area of bioinformatics. In Computer Science, Ogihara's work on biological computing similarly has overlap with bioinformatics. The Brain and Cognitive Science department, and the newly created Biomedical Engineering department both have strong overlap with the field of neuroscience (see more below). Biomedical engineering also has McGrath, who studies cell mechanics and motility, and Waugh, who studies mechanical properties of cell membranes and other subcellular components.

B - Medical Center

The presence of our expanding Medical Center has the potential to be a truly major advantage that Rochester has over many other Universities, when it comes to trying to recruit in Biological Physics. It is not just the presence of first rate research activities that is a draw, but specifically it is their close proximity to campus. A recent candidate for a position in bioinformatics at the Medical Center particularly stressed what a great asset it was if a researcher could conveniently walk from his academic base on campus, where he teaches and holds office hours, to the medical center which may serve as a base for some of his research activities. He pointed to his present situation at Washington University, where parking issues alone (the Wash U Medical Center is about 2 miles from campus) set up substantial obstacles to smooth collaborations between the Medical Center and academic departments.

Our committee held several meetings with faculty in the Medical Center, including members of the new research centers housed in the Aab Institute of Biomedical Sciences [25]. We have been impressed with the many current and emerging opportunities for collaborations with physicists, and with the enthusiasm with which our inquires were greeted. Three areas in the medical center were identified as being particularly promising.

Structural Biology and Biophysics

The field of structural biology uses physical tools to determine the structure of biological macromolecules (proteins, RNA, DNA) and macromolecular complexes. X-ray crystallography and NMR spectroscopy are the principal tools used in this research. Optical methods are often used to probe fluctuations in macromolecular structure. Rochester has an active and fairly large effort in this area that includes faculty from the Department of Biochemistry and Biophysics in the Medical Center and from the Department of Chemistry (Bren, Krugh, Miller, Turner). These faculty are formally linked through the Medical School’s "GEBS" (Graduate Education in the Biological Sciences) cluster in Biophysics and Structural

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Biology [26]. This particular cluster is responsible for the PhD degree program in Biophysics. Our committee met with Bill Bernhard, director of the cluster and a Biochemistry and Biophysics faculty member. Bernhard enthusiastically stated that hiring a physicist working on biological problems at the molecular level would be a significant asset to the biophysics cluster, and stated that he would be happy to promote interactions, including possible membership for such a person in the cluster. He thought that recruiting one person in this area made sense because of the many possible collaborators and the existing infrastructure. He mentioned techniques such as optical tweezers, atomic force microscopy, and spectroscopy of protein dynamics, that he thought would be promising. He cautioned, however, against someone whose primary concern was too specifically on instrumentation. He expressed his view that NIH was very supportive of interdisciplinary research, and recognized the importance of bringing in physics.

Neuroscience

Neuroscience research at Rochester is strong, broad and highly collaborative [27]. It is represented in both the Medical Center (Department of Neurobiology and Anatomy, Center for Aging and Developmental Biology) and on the River Campus (Department of Brain and Cognitive Sciences, Center for Visual Sciences). Based on this strength, an initiative in "Perceptual and Neural Systems" is one of three main programs within the new Department of Biomedical Engineering. Nationally and internationally, problems in the neurosciences have emerged as an important area of fundamental and applied biological physics. The committee met with Howard Federoff, who directs the Aab Institutes Center for Aging and Developmental Biology, and with Gary Paige, Chair of Neurobiology and Anatomy. Both were very interested in the possibility of collaboration with Physics. Federoff mentioned existing collaborations his group has with Miller and Rothberg in Chemistry, and with Ogihara in Computer Science. Paige was particularly enthusiastic. He pointed out to us that a recent search in his department had produced three applicants with deep training in physics, and it was his perception that a joint appointment and perhaps even some shared research space was not out of the question for a new appointment in Biological Physics. Both Federoff and Paige offered to help review candidates if we have a search that proceeds in this direction

Bioinformatics and Computational Biology

This is the least developed and the most poorly defined of the three areas, but it deserves mention because of its potential significance for Biological Physics. While there currently is no formal bioinformatics group in the Medical Center, it has been recognized that the formation of such a group is vital to the mission of the new research centers. A search committee has been formed that includes Dr. Richard Insel, director of the Aab Institutes Center on Human Genetics and Molecular Pediatric Disease and Deborah Cory-Slechta, Associate Dean for Research in the Medical School. Recruitment of 5-6 faculty in this area is anticipated, and several applicants have visited campus earlier this year. Of these, two of three had either a current or previous direct background in statistical physics. The medical Center appears to be interested in the participation of River Campus departments in this process, and Teitel has been invited with other River Campus representatives to meet with visiting candidates.

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IV - Funding Prospects

The prospects for obtaining external funding in support of a program in Biological Physics appear at present to be excellent. Shown in Appendix D is a chart of federal research funding for different disciplines from 1970 to 2000, compiled by American Association for the Advance of Science. It shows that while funding for physical sciences or engineering remains almost constant (~$5 billion) throughout the three decades, funding for life sciences during the same period has tripled, from ~ $5 billion to $17 billion in constant FY 2001 dollars. In Appendix E we list recent federal funding obtained by some of the prominent groups discussed in section II. NSF funding for these groups appears quite high, and one is impressed by the broad scope of the NSF programs through which funding has been obtained.

As indicated in the quotation from Harold Varmus at the beginning of section II, and as supported by the conversations we had with faculty at the Medical Center, NIH is also a major, and presumably increasing source of funding for physics based Biological Physics research. Six of the nine experimentalists listed in Appendix E have NIH funding. An example of NIH movement to fund in this area is a recent new initiative on "Single Molecule Detection And Manipulation" [28].

Most of the investigators listed in Appendix E are senior. Some however, such as Quake and Kas, are more junior. As further evidence of the ability of young investigators in this field to get funding, we list in Appendix F the NSF funding obtained by both the recent biologically oriented appointments in the Institute of Optics. Berger has been at the UR only about 8 months. Novotny has been at the UR about a year and a half. Both succeeded in getting NSF funding on their first tries.

In addition to funding sources targeting specifically Biological Physics, the molecular scale of the systems of interest make such research programs natural competitors for funding under new nanoscience initiatives that have been launched by both NSF and DOE.

Finally, the field of Biological Physics is also supported by private foundations such as the Whitaker Foundation [29] and the Keck Foundation [30] which offer grants to young investigators. Kas from Texas-Austin, for example, has grants from both the Witaker and Keck Foundations.

V - Recommendations

In its 1997 report, the Faculty Recruiting Strategy Committee listed a set of "golden rules" that it felt should guide recruitments into the department. These rules included: (1) "Respond to scientific urgency"; (2) "Make timely investments in new fields"; (3) "Preserve funding stability of our groups"; (4) "Maintain critical mass and replace key personnel"; (5) "Preserve both the quality and supply of superior graduate students".

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We believe that all the above rules unequivocally argue that an appointment in Biological Physics should be made as soon as possible.

Biological/biomedical research is clearly a field in scientific ascendance. Along with the growth in scientific interest there has been, and will continue, a corresponding growth in the availability of external research funding. One needs only to look at the expansion of research at our Medical Center and the creation of the new Biomedical Engineering Department here at the UR to see the reality of this. As outlined in section II, the tools and ideas of physics now place our field on the threshold of being able to make important new contributions in the biological/biomedical area. That Biological Physics is an exciting and rapidly growing field has attracted the attention and the investment of virtually all the top physics departments in the country. We believe that an appointment in Biological Physics thus satisfies golden rules (1), (2) and (3).

The Department of Physics and Astronomy at the UR has had for many years an active program in Biological Physics, through the presence of Bob Knox (a recent winner of the APS prize in Biological Physics) and the joint appointment of Tom Foster. Both have had successful and visible single investigator programs. Knox, though still an active presence in the department, officially retired in 1997 and has since worked only with undergraduate students. Although the department is now considering making additional joint appointments in the area of biological/medical physics, the committee feels that for the department maintain a distinguished program in Biological Physics, a full time faculty appointment is imperative. We believe that an appointment in Biological Physics thus satisfies golden rules (4) and (5). Appendix G lists the major subfields of first-year graduate students in 1997-98 from AIP 1998 Graduate Student Report: First Year Students. By the end of their first year of graduate study, 4% of domestic students and 2% of foreign students have chosen biophysics as their research specialty.

In section III we outlined the environment of existing research at the UR into which a new faculty in Biological Physics would arrive. We believe this environment, spread across the College and the Medical Center, is broad based, is highly conducive to establishing interdisciplinary interactions, and will be attractive to potential candidates (see more below). The presence of Foster, who has appointments in the Medical School, Optics, and Physics, will facilitate such interactions. In section IV we presented evidence of a bright funding outlook for support of new single investigator programs in Biological Physics. We therefore believe that all the ingredients exist to establish a new, successful, program in Biological Physics here at the UR.

Finally, we address the question of whether the establishment of such a successful program in Biological Physics would have a significant positive impact upon the department. One might argue that since Biological Physics is to be relegated to a single FTE in our department, that even a successful program could not make a dramatic impact on the national visibility and ranking of the department. In this respect, we believe that an appointment in Biological Physics represents an investment in the long range future of the department. Not to make such an appointment will leave the department without a presence in one of the major new emerging areas of physics. A successful appointment in this area, on the other hand, may lead to growth

10 and recognition at the national level. The time for such an appointment is now, when the field is still relatively young and growing, rather than later when one will be forced to "catch up" with more established groups elsewhere. The committee believes that the following three specific areas represent the likely best targets for recruitment in Biological Physics:

1. Single molecule techniques: An appointment in this area appears to be a natural choice for Rochester, building upon the department's and the University's reputation and strength in optics. An appointment in this area may also allow for branching out into optical investigations of nanostructures more generally, another hot and growing field. For an appointment to be successful in this area of Biological Physics, however, we believe it is important to find someone who demonstrates a good understanding of the biological questions worth pursuing with such methods, rather than someone whose interests are focused on the technique itself.

2. Neuroscience: We believe that the strong multidisciplinary activity in this area at the University makes it an attractive one. The topics and speakers at the forth coming ITP workshop "Dynamics of Neural Networks" [17] represent good examples of the sort of ways physics can contribute to this field. The presence of physics in this field is perhaps less advanced than it is for single molecule techniques, but this may also be an opportunity for us to get into the field early.

3. Bioinformatics: The mapping of the human genome makes this subject clearly one of the major scientific initiatives of the future. A successful appointment in this area could therefore bring the department into this high impact area. This was the area specifically recommended by Albert Libchaber when he visited UR to advise the committee two years ago. Proceeding in this direction however would be premature until it becomes clear what concrete steps the Medical Center takes to establish a group in this area.

Although the above seem at present to be the best targets, we believe that a recruitment should be broadly advertised for any field of Biological Physics, specifying the above three fields only as potential areas of interest. The goal of attracting an individual of the highest quality should outweigh programmatic concerns. It should however be recognized that a recruitment in Biological Physics can easily extend over more than one year, due to the highly competitive nature of the current market.

The committee therefore recommends that the field of Biological Physics be given high priority for the next available faculty recruitment.

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References

[1] L. Garwin, "US universities create bridges between physics and biology", Nature 397, 3 (1999)

[2] Editorial note, "Can physics deliver another biological revolution?", Nature 397, 89 (1999)

[3] H. Varmus, "The impact of physics on biology and medicine", APS News August/September 1999, condensed from lecture at the APS Centennial Meeting, March 1999, available at http://www.nih.gov/welcome/director/varmus.htm

[4] H. Varmus, "Squeeze on Science", op-ed article, Washington Post, Oct. 4, 2000, p. A33.

[5] Science 283, 1593 (1999).

[6] Chemical Physics, Vol. 247 #1 August (1999).

[7] Chu: http://www.stanford.edu/dept/physics/people/faculty/chu_steven.html

[8] Block: http://www.stanford.edu/dept/app-physics/ar/facname.html#Block

[9] Moerner: http://www.stanford.edu/dept/chemistry/faculty/moerner/

[10] Quake: http://thebigone.caltech.edu/quake/research.html

[11] Bensimon: http://www.lps.ens.fr/recherche/biophysique-ADN/

[12] Weiss: http://www.lbl.gov/msd/chemla/members/weiss.html

[13] Libchaber: http://www.rockefeller.edu/labheads/libchaber/libchaber.html

[14] Craighead: http://www.hgc.cornell.edu/index.html

[15] Austin: http://PUPGG.PRINCETON.EDU:80/%7Erha/

[16] http://matisse.ucsd.edu/itp-bioinfo/

[17] http://www-physics.ucsd.edu/neurophysics/itpworkshop.html

[18] Leibler: http://www.molbio.princeton.edu:80/faculty/leibler.php

[19] Kas: http://chaos.ph.utexas.edu/~kas/

[20] Kleinfeld: http://www-physics.ucsd.edu/neurophysics/missionstatement.html

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[21] Shakhnovich: http://paradox.harvard.edu/

[22] Onuchic: http://guara.ucsd.edu/

[23] Hwa: http://matisse.ucsd.edu/~hwa/

[24] Siggia: http://www.rockefeller.edu/labheads/siggia/siggia.html

[25] http://www.urmc.rochester.edu/Aab/

[26] http://www.urmc.rochester.edu/GEBS/bsb/

[27] http://broca.bcs.rochester.edu/neuroscience/

[28] http://grants.nih.gov/grants/guide/pa-files/PA-01-049.html

[29] http://www.whitaker.org

[30] http://www.wmkeck.org

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Appendix A Charge of the Committee

Overall Charge:

Should the department plan to have a program in Experimental Biological Physics with only one single Physics faculty appointment and with one or more joint appointments in other departments.

Items for consideration:

1. In the short term, coordinate Biological Physics colloquia(*) with the aim of educating the department about the sub fields of Biological Physics that may be appropriate for our department.

2. Is it required that a Biological Physics program in our department be connected with programs and facilities in other departments, and what should be the nature of that connection?

3. Compile a list of faculty and investigators at the UR and local area institutions are doing Biological Physics related work.

4. What are the funding sources for such a position?

5. What kind of facilities, startup funds etc. are needed?

6. Can a single investigator in the department of Physics and Astronomy make a major impact in the field? Can a single appointment in Biological Physics have an impact on our future national rating? On our future graduate recruiting?

7. Can a small department such as ours plan on a program which relies only on more joint appointments (e.g. the new Chair in medical imaging in Optics) similar to the present plasma physics program in ME and the Laser Lab.?

Verbal interim report to the faculty to be made in September 99. Final report to faculty (written) May 99.

(*) Foster agreed that current budget for seminars in Biological Physics be used instead to help bring colloquium speakers in this field.

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Charge as revised by the committee Overall Charge:

Should the department actively pursue an appointment in the field of Biological Physics as one of the next highest recruitment priorities?

For Consideration:

(1) What is the rational for such an appointment in the Physics & Astronomy Department?

(2) What interactions with other segments of the University Community are necessary for such an appointment to be successful?

(i) What resources/facilities at the University are available/necessary? (ii) What are the possibilities for collaboration with other researchers at the University? at nearby institutions?

(3) Can the Department have a successful program, that makes an impact in the field, given the limited opportunities for growth of any new subfield as implied by our Department's fixed size?

(4) Can the Department hope to attract an outstanding person in this field? What type of startup funds/resources are needed?

(5) What are the prospects for research funding for such a position?

(6) What would be the overall impact of such an appointment upon the Department? Would it boost our visibility? Would it foster larger interdisciplinary activities? Would it help graduate recruitment?....

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Appendix B Invited Colloquium Speakers in Biological Physics

April 22, 1998 Robert Austin, Department of Physics, Princeton University Adventures in Flatland (http://PUPGG.PRINCETON.EDU:80/%7Erha/)

April 28,1999 Albert J. Libchaber, Rockefeller University DNA Mode d'Emploi (http://www.rockefeller.edu/labheads/libchaber/libchaber.html)

April 12, 2000 Prof. Watt W. Webb, Dept. of Applied Physics, Cornell University Biophysics with Multiphoton Microscopy and Correlation Spectroscopy Fluorescence (http://www.aep.cornell.edu/FFR/Faculty/Webb.html)

April 18, 2001 Prof. Sol Michael Gruner, Dept. of Physics, Cornell University The Bicontinuous Mesophase Materials: Lessons From Biology (http://bigbro.biophys.cornell.edu/)

Note: The visit of Austin preceded the official consitution of our committee.

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Appendix C UR Faculty from Other Departments Interviewed by the Committee

Douglas H. Turner, Professor of Chemistry

Thomas R. Krugh, Professor of Chemistry

Kara L. Bren, Assistant Professor of Chemistry

Shaul Mukamel, Professor of Chemistry

Christoph Dellago, Assistant Professor of Chemistry

Todd D. Krauss, Assistant Professor of Chemistry

Robert C. Angerer, Professor and Chair of Biology

Andrew Berger, Assistant Professor of Optics

Lukas Novotny, Assistant Professor of Optics

David Williams, Professor of Brain and Cognitive Sciences, Allyn Chair of Medical Optics, and Director of the Center for Visual Sciences.

Mitsunori Ogihara, Associate Professor and Chair of Computer Science

William A. Bernhard, Professor of Biochemistry & Biophysics and Director of Biophysics and Structural Biology

Howard J. Federoff, Professor of Neurology, Molecular Medicine and Gene Therapy; Chief, Molecular Medicine and Gene Therapy; Director, Center for Aging and Developmental Biology

Gary D. Paige, Professor of Neurology, Ophthalmology, Neurobiology and Anatomy, Surgery (Otolaryngology) and Brain & Cognitive Sciences; Unit Chief, Sensory Motor Neurology Unit; Chair, Department of Neurobiology and Anatomy

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Appendix D Trends in Federal Research by Discipline

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Appendix E Sources of Funding of Established Groups in Biological Physics

Below is listed the agency, grant title, grant amount, and agency program for recent bioligically related research grants of the listed individuals (note: NIH website did not provide funding levels of grants).

Steven Chu, Stanford NSF - Polymer Dynamics and Biophysics with Single Molecules $1,300,000 (1248 Physics-Other)

Steven Block, Stanford NIH - Transcription Studied at the Molecular Level (National Institute of General Medical Sciences)

W.E. Moerner, Stanford NSF - Single-Molecule Optical Probes of Protein Biophysics $300,000 (1164 Molecular Biophysics)

Stephen Quake, CalTech NSF - XYZ on a Chip: Integrated Microfluidic Analysis System $510,000 (1406 Thermal Transport & Therm Proc) NSF - A Microfabricated Cell Sorter for Molecular Evolution $109,060 (1402 Biochemical & Biomass Eng) NSF - CAREER: Polymer Physics with DNA $407,398 (9134 EDucation & Interdiscip Resear) NIH - FLuorescent Photobleaching Method For Sequencing Dna (National Center For Human Genome Research)

Shimon Weiss, LBL NIH - Development Of Q-Dots As Biological Probes (National Center For Research Resources)

Stan Leibler, Princeton NSF - Physical Aspects of Self-Correcting Assembly and Force Generation in Cytoskeleton Proteins (Libchaber is co-PI) $1,273,073 (9134 Education & Interdiscip Resear) NIH - Robustness And Individuality In Bacterial Chemotaxis (National Institute Of General Medical Sciences)

Robert Austin, Princeton

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NSF - XYZ on a Chip: Engineering of Innovative Molecular Sieves on a Chip by Nanoprint Lithography $459,931 (1519 Integrative Systems) NSF - NANOSCALE: Nanoscale Magnetics in Biology $100,000 (1467 Materials Processing & Manufct) NSF - Microlithographic Manipulation of Macromolecules $425,000 (1164 Molecular Biophysics) NSF - Mechanical Rigidity of DNA and its Relation to DNA-Protein Interactions $298,300 (1144 Biomolec Struct & Funct)

Josef Kas, Texas-Austin NSF - Microscopic Origin of the Viscoelasticity of the Cytoskeletal Rim and the Impact on Shape and Mechanical Resistance of Cells $270,000 (1132 Cellular Organization) NIH - Control Of Cell Elasticity By The Actin Cortex (Nat Inst Of Arthritis And Musculoskeletal And Skin Diseases)

David Kleinfeld, UCSD NSF - Imaging Study of Single Neuron Computation in Leech $300,000 (1162 Computational Neuroscience) NSF - IGERT Full Proposal: Computational Neurobiology Graduate Program $2,700,000 (1335 IGERT Full Proposals) NSF - Third Harmonic Microscopy: Dynamic, High-Resolution, Three-Dimensional Imaging Without Bleaching $344,773 (1108 Instrumentat & Instrument Devp) NSF - Role of Propogating Oscillations in Reptilian Visual Cortical Processing $165,000 (1162 Computational Neuroscience) NSF - Modern Biophysical Principles and Instrumentation $259,749 (9134 Education & Interdiscip Resear) NSF - Two-Photon Laser Scanning Microscope for Developmental/Cell Biologists $231,544 (1108 Instrumentat & Instrument Devp ) NIH - Optical Imager For Electrical Dynamics In Cortex (National Center For Research Resources) NIH - Deep Multi-Photon Imaging Of Brain Structure & Function (National Inst Of Neurological Disorders And Stroke) NIH - Motor Modulation Of Sensory Input In Rat Vibrissa Cortex (National Institute Of Mental Health)

Eugene Shakhnovich, Harvard NSF - Thermo-mechanical Processes in Chemically Disordered Gels and Networks: Toward Molecular Design of Responsive Materials $288,000 (1765 Materials Theory)

Jose Onuchic, UCSD

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NSF - Computational Laboratory For The Development Of New Approaches To Complex Biological Phenomena $100,000 (1108 Instrumentat & Instrument Devp ) NSF - Biocomplexity: From Gene Expression To Morphology And ulticellular Organization In Dictyostelium $2,999,982 (1154 Biochemistry Of Gene Expressio) NSF - Understanding Protein Folding: Quantitative Connections Between Energy Landscape Theory And Experiments $750,000 (1164 Molecular Biophysics) NSF - Understanding Protein Folding: From Lattice Models Towards Real Proteins $543,000 (1164 Molecular Biophysics) NSF - Theoretical Methods For Dissecting Electron Tunneling Interactions In Proteins $285,000 (1164 Molecular Biophysics) NSF - Electron Tunneling Pathways In Modified And Native Proteins $253,000 (1164 Molecular Biophysics)

Terence Hwa, UCSD NSF - Statistical Mechanics of Sequence Matching $225,000 (1765 Materials Theory)

Eric Siggia, Rockerfeller NSF - Theoretical Condensed Matter Physics $411,000 (1765 Materials Theory)

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Appendix F Sources of Funding of Recent Biologically Related Faculty at the Institute of Optics

Andrew Berger NSF - Biophotonics: Frequency-modulated Raman Spectroscopy of Biological Specimens $222,295 (5345 Biomedical Engineering)

Lucas Novotny NSF - Development of a Near-Field Optical Instrument for the Study of Semiconductor Nanostructures and Student Training $300,000 (1189 Major Research Instrumentation) NSF - Biophotonics: Near-field Raman Microscopy of Biological Membranes $269,239 (5345 Biomedical Engineering)

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Appendix G Major Subfields of First-Year Graduate Students

Table 7. Major subfields of first-year students enrolled in a physics or astronomy program who have plans to receive a PhD, 1997-98.

US Citizens Foreign Citizens

Undecided 22 24 Astronomy / Astrophysics 18 8 Particles and Fields 13 13 Condensed Matter 12 25 Atomic and Molecular 6 3 Nuclear 4 5 Optics/ Photonics 4 4 Biophysics 4 2 Materials Science 3 3

Source: AIP Statistics Division, 1998 Graduate Student Report.

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