Special Issue Preface pubs.acs.org/JPCB
Biography of William M. Gelbart
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At Berkeley Bill continued work on gas-phase photophysics theory with his first postdoctoral student, Donald Heller, but in collaboration with his first Ph.D. student, David Oxtoby, and with his new faculty colleague and friend Robert (“Bob”) Harrishe devoted most of his efforts to developing manybody theories of higher-order optical properties of simple fluids, including both multiple-light-scattering and collision-induced effects. After just a couple of years working in this new field at Berkeley, Bill decided to accept an offer from UCLA, where several of his soon-to-be colleaguesin particular, Daniel Kivelson, John McTague, Howard Reiss, Robert (“Bob”) Scott, and Charles (“Chuck”) Knoblerhad also already begun work on light and neutron scattering, nucleation and critical phenomena, and surfaces. Moving to UCLA in 1975 gave added impetus to his entry into this new area, which was a presaging of the eventual shift of the field of physical chemistry itself, over the next decade or two, from high-resolution gasphase spectroscopy and chemical kinetics to the statistical mechanics and bulk properties of liquids, aqueous solutions, and “materials”. In the late 1970s, with the exception of some work with Eric (“Rick”) Heller on vibrational “local modes”, and with his Ph.D. students Mark Elert and Paul Stannard on photodissociation and photoelectron spectra, Bill worked almost exclusively on formulating a generalized van der Waals theory of liquid crystals, which self-consistently combined a mean-field treatment of angle-dependent attractions with the Onsager theory of “hard” anisotropic particles. This work provided a natural basis for connecting liquid-crystal phenomena in thermotropic (“neat”) liquids with those in “lyotropic” (colloidal) solutions. With his postdoctoral student Boris Barboy he also developed a new representation (the “y-expansion”) of pressure equationsof-state for hard-particle fluids, which allowed for accurate, analytical predictions of the orientational-ordering phase transitions undergone by interacting repulsive particles with arbitrary shapeprolate or oblate, uniaxial or biaxialand which accounted for the weakness (“almost second-orderness”) of the first-order isotropic−nematic transition in most liquidcrystal systems. In 1980, on the occasion of a sabbatical-leave visit to UCLA by Avinoam (“Avi”) Ben-Shaul from the Hebrew University of Jerusalem, Bill began thinking for the first time about the phenomenon of self-assembly. Having in mind the gel-toliquid-crystal phase transition in phospholipid bilayers, Avi had come to UCLA eager to work with Bill on biological membranes and self-assembling phospholipid bilayers. Their first joint work was on liquid crystals, not on membranesbut rather on an application of the generalized van der Waals theory to evaluate the splay, bend, and twist elastic moduli of nematics. Further, before tackling the statistical thermodynamics of lipid bilayers, they turned their attention to solutions of spherical and cylindrical aggregates of amphiphilic molecules.
ill grew up in upstate New York (Syracuse) and went to junior and senior high school in New Jersey (Teaneck), just a few miles from New York City. Even though he and his identical twin brother, Steve, did not get serious about their studies until halfway through college, they seemed to be clear all along about wanting to follow in their father’s footsteps as a research scientist and professor. (Their father, Abe, was a mathematician, and Steve also became a mathematician, so it was only Bill who left the family business.) Bill did his undergraduate work at Harvard University (B.S., 1967), majoring in Chemistry and Physics, where he enjoyed his first taste of research under the mentorship of William (“Bill”) Klemperer. This experience got him excited about excited molecules, but also confirmed his early preference for theoretical versus experimental work. Almost immediately upon starting graduate work at the University of Chicago (Ph.D., 1970) in the Fall of 1967, Bill began his doctoral thesis work under the mentorship of Stuart Rice, tackling a general theoretical approach to “radiationless transitions” in gas-phase molecular spectroscopy and photophysics. Throughout the course of his Ph.D. research he collaborated regularly with Karl Freed, who had just joined the faculty and with whom he had overlapped when Karl was a Ph.D. student in the Klemperer group. Bill worked closely as well with Joshua Jortner from Tel Aviv University who was a frequent visitor to Chicago. Several papers from this period clarified the way in which irreversible nonradiative relaxation could take place in isolated “large” molecules (the size of benzene or bigger) that acted as their own “heat bath”, converting electronic excitation into vibrational and rotational motion. These were the years when lowpressure and molecular-beam experimentsprobing singlemolecule gas-phase spectroscopy and kineticsdominated the world of physical chemistry (“chemical physics”). Other papers from Bill’s Ph.D. work focused attention on the breakdown of the Born−Oppenheimer approximation in “small” (e.g., triatomic) molecules and its consequences for proper interpretation of spectra and collisional quenching phenomena in these systems. With an NSF-NATO Postdoctoral Fellowship in hand, Bill spent most of 1971 in Paris, sitting 2−3 days a week with Lionel Salem and his group at the University of ParisOrsay, exchanging ideas about photochemical reactions in the gas phase. He spent the rest of the time learning aboutand writing his first paper onlight scattering and critical phenomena in simple fluids, a classic field in statistical physics that had just undergone a major renaissance in the 1960s with the advent of the laser and of scaling theory. Just before the end of his stay in Paris Bill metand formed a lifelong friendship withthe molecular spectroscopist Sydney Leach, with whom he continues to walk, talk, and exchange ideas to the present day. At the end of 1971 Bill moved to UC Berkeley, as a Fellow of the Miller Institute, which gave him another opportunity to work by himself. But within his first few months there he was hired as an Assistant Professor in the Department of Chemistry. © 2016 American Chemical Society
Special Issue: William M. Gelbart Festschrift Published: July 7, 2016 5789
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increasingly broad range of physical structures and processes on the average of once a day.) Bill’s new interest in DNA quickly inspired him to tackle the problem of DNA condensation and the breakdown of meanfield (e.g., Poisson−Boltzmann and Debye−Huckel) theories of counterion effects, and resulted in a series of several highly original papers involving important collaborations with Niels Gronbech-Jensen, Robijn Bruinsma, Andrea Liu, Mark Stevens and students Itamar Borukhov and Kun-Chun Lee. This early work on DNA was a natural continuation of his work with Avi on surfactant micelles and lipid bilayers, and indeedwith Avi and his students Daniel Harries and Sylvio Mayled naturally to the development of a systematic theoretical treatment of the electrostatic and self-assembly characteristics of the DNA/ cationic-lipid complexes whose physical properties and structures were being pursued experimentally by Cyrus Safinya and his group at UCSB and by Adrian Parsegian and coworkers at the NIH. Simultaneous with this increasingly biophysical direction in his research, Bill pursued throughout the 1990s a parallel program dealing with the rational synthesis and design of nanoparticles and their interactions in solution. First, with Rob Whetten, who was then a colleague at UCLA, he suggested an analogy between oil−water microemulsions stabilized by surfactant and the ligand stabilization of crystalline nanoparticles in solution, featuring the role of interfacial tension, curvature energy, and entropy of dispersion. This idea was continued with Jim Heath, who joined the UCLA faculty from IBM Yorktown Heights in 1994 and who was already focused on trying to control the size and shape of nanocrystals in solution. Together with their students Daniel Leff and Pamela Ohara, they predicted and demonstrated that thermodynamically stable gold nanoparticles could be synthesized with arbitrary and precise diameters by tuning the stoichiometry of alkyl thiols and gold salts in water. They went on to show that microphase separation and pattern formation of particles at the air−water interface could be controlled by varying the length of the alkyl thiol and the diameter of the metal core, confirming predictions being made by Bill and his postdoctoral student Richard Sear. The first biologically inspired problem that arose from his interest in stiff charged polymers like DNA and charged colloidal particles like protein aggregates was the organization of DNA and histones into nucleosomes and chromatin. With his Ph.D. student Stella Park and postdoctoral student Helmut Schiessel, Bill collaborated with Robijn Bruinsma throughout the late 1990s on simple models of the electrostatic stabilization of stiffly charged chains by oppositely charged spheres, and on the structure and dynamics of the resulting complexes. Several years earlier, through his long-time friendship with Ben Widom, Bill had met Ben’s older son, Jon, a brilliant biologist and acknowledged expert on DNA condensation, nucleosomes, and chromatin. Bill and Jon had never collaborated because their research interests hadn’t overlapped, but at this point in the late 1990s they began immediately to work together, publishing in 2001 an intriguing suggestion, with Helmut Schiessel and Robijn Bruinsma, for how polymer reptation could account for the repositioning of bound nucleosomes. This collaboration was ended almost immediately by Bill’s “viral epiphany”, which blossomed in the same year; Jon joked then that the only way they could continue to work together on what they were both equally passionate about would be to focus on the few viruses whose DNA genomes are complexed with the histones stolen
Existing theories had neglected interactions between aggregates, leading to simple “growth laws” for the increase in size of rod-like micelles with overall surfactant concentration. With graduate student Bill McMullen, Avi and Bill showed how interactions between aggregates affected the self-assembly process itself. In particular, they showed that the “sphere-torod” transition in solutions of surfactant micelles was enhanced by interactions between them, and that the onset of long-range orientational ordering favored still longer micellar rods. Thanks to Avi staying for a follow-up sabbatical year, they also generalized their theory from dilute solutions of interacting micelles to concentrated ones in which the finite rods give way to disks or to hexagonal phases and ultimately to lamellar states. Finally, with postdoc Yitzhak Rabin they elucidated the succession of uniaxial and biaxial nematic liquid-crystal phases that arise in mixtures of rod-like and plate-like particles. Several years later, in the late 1980s and early 1990s, Bill and Avi returned to the problem of interactive micelles, treating explicitlywith their students Carey Bagdassarian, Didier Roux, Massimo Noro, Yardena Bohbot, and Rony Granek curvature defects in lamellar phases and smectic-to-bilayer transitions in concentrated surfactant solutions. During this period they also studied the conformational statistics of amphiphile chains in micelles and bilayers. An elegant statistical-thermodynamic theory of alkyl chain packing in arbitrary (spherical, cylindrical, and planar bilayer) geometries was formulated, by maximizing the chain free energy subject to a constant-density constraint, yielding a simple expression for the probability distribution of chain conformations in any given geometry. With graduate student Igal Szleifer they applied the theory to calculate properties such as chain orientational bondorder profiles and segment spatial distributions, showing excellent agreement with experiment. Among the best known applications of this theory, which in addition to Igal also involved Diego Kramer, Jean-Louis Viovy, Sam Safran, and Didier Roux, has been the calculation of the bending constants of pure and mixed lipid bilayers. In 1995, together with Didier Roux, Bill and Avi edited a comprehensive volume entitled Micelles, Membranes, Microemulsions and Monolayers, with contributions from many of the leading researchers in these fields. Bill and Avi collaborated during these years on several other topics, including the statistical thermodynamics of defects and the failure of solids (with postdoctoral students Robin Selinger and Zhen-Gang Wang, and collaborators Uzi Landman and Ruth Lynden-Bell), on micellar flow (with Robijn Bruinsma and postdoctoral student Shi-Qing Wang), and monolayer phase transitions (with postdocs Zhong-Ying Chen, Maria Costas, and Diego Kramer). By the late 1990s their work was still mainly focused on self-assembling systems, but with a slow (and, it turned out, irreversible) shift toward problems of biophysical interest. Much of this work was done in cafes, in Los Angeles and Jerusalem as well as in New York and Paris. Bill, as his friends know well, is an extremely enthusiastic and irrepressible scientist, especially upon encountering an exciting new field of research. Avi remembers one cafe meeting in New York in 1995, shortly after Bill first became fascinated by the physical properties of DNA, when Bill pulled out his belt, stood up abruptly (catching the attention of many “innocent bystanders”), and started demonstrating the different roles of twist and writhe in the phenomenon of supercoiling. (To this day, 20 years later, members of his research group attest to the fact that his belt comes off for similar purposesillustrating an 5790
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to complete the packaging of the genome. These values were in excellent agreement with single-molecule measurements that were published at the same time by Doug Smith, Carlos Bustamante, and their co-workers. Bill and Avi and their students also predicted that internal pressures on the capsid walls would reach values up to 50 atm, and suggested that it should be possible to inhibit the ejection of the highly pressurized DNA from the capsid by counterbalancing the ejection force with an external, osmotic, pressure. Earlier discussions in Paris, with Eric Raspaud and Francoise Livolant (University of ParisOrsay), had suggested that one might be able to measure the pressure in a DNA virus by controlling the osmotic pressure in solution. More explicitly, if one adds to a solution of purified virus the membrane protein that is the host-cell receptor for the virus, ejection of the genome will be triggered, and the ejection will continue until all of the DNA is relieved from the stress of its confinement. If, on the other hand, a known amount of calibrated osmolyte is present in the solution, corresponding to a given osmotic pressure, ejection will proceed only to the point where the pressure inside the capsid has dropped to the value outside. By measuring how much DNA remains inside, as a function of external pressure, one can determine the pressure exerted by the confined DNA as a function of its length; the pressure required to keep all of the genome inside is the pressure of the intact virus. Because Bill did not have a lab at the time, and was not even thinking about doing experiments on viruses, it was agreed that Eric and Francoise and their co-workers at Orsay would try an experiment of this kind. In the meantime, Bill continued to talk about this experiment in seminars and conference talks whenever he presented the theory of viral DNA packaging. At one such presentation in 2001, in Sweden, he was approached afterward by an enthusiastic Ph.D. student, Alex Evilevitch, who asked if he could join Bill’s lab as a postdoctoral student and try the experiment. To Alex’s credit, he was still eager to come to UCLA even after Bill explained that he did not have a lab... This immediately set in motion a discussion back at UCLA, with Chuck Knobler, who had been thinking of retiring, but who was easily convinced tonot do so, but instead tojoin Bill in attempting to carry out biology experiments at UCLA. It was agreed with Eric and Francoise that they would continue work with T5 phage at Orsay and that Bill and Chuck would begin work in parallel with lambda phage at UCLA. Accordingly, in the summer of 2001, just after having moved to UCLA from Sweden, Alex participated in a two-week molecular biology “boot camp” sponsored by New England Biolabs, and was ready to start growing and purifying virus. The only “hitch” was that Chuck’s lab at UCLA contained none of the equipment or reagents necessary to carry out the work, and neither Bill nor Chuck had studied any biology or acquired any knowledge of it during their decades of research in physical chemistry and soft-condensed-matter physics. Fortunately, their structural biology colleague Richard (“Dick”) Dickerson was intrigued by the experiment and generously offered bench space, equipment, and reagents in his lab. Bacteriologist Jim Gober, another faculty colleague in the Department, provided expert instruction in growing bacteria and infecting them with phage. Laurence Lavelle, a former postdoctoral student of Dick’s and a lecturer at UCLA, soon joined the effort, contributing the very useful idea that DNase could be used to distinguish between ejected and unejected DNA in the presence of different concentrations of osmolyte. Against all
from their host cell. But the close friendship they had developed was to grow and intensify over the next dozen yearsuntil Jon’s sudden and untimely death in 2012as they met as often as they could throughout the States and Europe to talk science and cook and eat together. Bill’s “viral epiphany”the dramatic switch from theoretical studies of simple models of DNA and protein in solution to an all-out, theoretical and experimental, program on viruses and “how they work”had its roots in his 1998−99 sabbatical year. In the Fall of 1998 he, Phil Pincus, and Adrian Parsegian organized a workshop on “Electrostatics in Biology” at the Institute for Theoretical Physics in Santa Barbara. There he started to read and think about viruses, which had first been called to his attention as a possible research pursuit for him by Gary Fujii, with whom he had collaborated earlier in the decade on liposome biophysics. Bill was intrigued by Gary’s observation that the polyvalent-counterion-induced DNA condensates he had been studying were reminiscent of the close-packed, hexagonally ordered, DNA genomes confined in viral capsids. The Spring (1999) of his sabbatical year was spent as Rothschild Professor at the Curie Institute in Paris, where he had still more time to learn about viruses. It was natural for him to focus first on DNA viruses, exploring how the physical properties of DNA are related to the physical properties of viruses, and in particular to their mode of genome delivery. In Paris, through discussions with phage biologist Lucienne Letellier (University of Paris-Orsay) and with membrane protein biologists Jean-Louis Rigaud and Olivier Lambert (Curie Institute), he saw for the first time electron micrographs of bacterial viruses binding to host cell receptors and ejecting their DNA genomes. The first virus-related experiment he designed was with them, involving purified T5 phage and liposomes reconstituted with their receptor protein (FhuA) and filled with concentrated solutions of the polyvalent cation spermine. Electron micrographs of this system showed clearly how the viruses were “tricked” into “thinking” that the receptorpresenting liposome was a bacterial host, and in particular how the injected genomes form a toroidal condensate inside; a falsecolor image of one of these micrographs made a striking cover of the 2000 Physics Today issue in which an invited review on DNA electrostaticsby Bill, Robijn Bruinsma, Phil Pincus, and Adrian Parsegianappeared later that same year. Upon his return to UCLA in the Fall of 1999, Bill and Avi started corresponding about how they might treat theoretically the confinement of DNA genomes in viral capsids. Again, it was an electron micrograph picture that inspired themin particular, the iconic image from 1962, by Kleinschmidt et al., in which a broken (osmotically shocked) viral capsid is seen in the presence of its now-free/unconfined DNA genome. The linear dimension of the DNA is about 10 times that of the capsid, suggesting a dramatic release of pressure. Theoretical studies were undertaken with Avi’s Ph.D. student Shelly Tzlil and Bill’s postdoctoral student James Kindt, in which they calculated the forces and pressures associated with the packaging of viral DNA into its capsid. In the case of bacteriophages, for example, the DNA is tens of microns long, the capsid diameter is only about 50 nm, and the genome is strongly bent and close-packed at essentially crystalline density. In two papers published in 2001 and 2003, they presented a molecular dynamics simulation and phenomenological theory of the loading and ejection process, predicting that loading forcesexerted by the virally encoded packaging motor proteinwould have to reach magnitudes as high as 50 pN 5791
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thermodynamic processand the formation of micellar aggregates; an experimental paper a few years later, with UCLA colleague Tom Mason and his student Connie Chang, extended this analogy by literally combining viral capsid protein with oil/water micro(nano-)emulsion droplets and demonstrating the dependence of capsid stability on curvature. Further theoretical work was carried out in the able hands of postdocs Markus Deserno, Toan Nguyen, and Peter Princen, on models of viral budding and capsid elasticity. By 2004, Bill and Chuck had begun experiments on simple RNA viruses, which are known to self-assemble as infectious units, from their purified components. They chose to work with the plant virus, CCMV, which was the first (in 1967) spherical virus to be reconstituted from its constituentscapsid protein and viral RNA. John (“Jack”) Johnson at the Scripps Research Institute in La Jolla generously offered to host one of their studentspostdoc Jean-Philippe Michelin his lab, to learn how to grow CCMV, purify it, take it apart, and put it back to together again. The first experiments with CCMV at UCLA were done by postdoc Yufang Hu with synthetic anionic polymer replacing the viral RNA, because Bill and Chuck thought that it would be easier than RNA to work with and characterize, but they quickly switched to viral and nonviral RNAs. UCLA colleague Sabeeha Merchant, a plant biochemist, provided helpful advice on growing plants and infecting them with virus, which was done in a tiny storage closetthe “Harry Potter room”squeezed under a set of stairs. Sabeeha also called to Bill and Chuck’s attention the work of A. L. N. Rao (“Rao”), a plant virologist at UC Riverside with whom they have been collaborating often and productively ever since. Also at this time Jaime Ruiz-Garcia, a former postdoc of Chuck’s from his Langmuir monolayer days, started visiting Bill and Chuck’s lab from San Luis Potosi, Mexico, and quickly became “infected” by CCMV self-assembly work, collaborating closely up to the present and sending some of his best students to UCLA as Ph.D. and postdoc students. Work on a simple enveloped virus, one in which the capsid is surrounded by a lipid bilayer membrane, as is the case with most mammalian viruses, was begun in 2005, during Bill’s 2004−5 sabbatical year, following his term as Chair of Chemistry and Biochemistry at UCLA. All of Bill’s three preceding sabbatical years had been spent in Paris because his wife Nina is a historian of 18th-century France, including history of science and medicine; but this sabbatical was different because he was setting up a lab for the first time and wanted to be close to it. So trips to Paris with Nina now took the form of more frequent and significantly shorter visits, and Bill spent the year 2004−5 at Caltech collaborating with Rob Phillips on several theoretical and experimental projects of mutual interest involving DNA viruses. But much as he had settled earlier on CCMV as the simplest “naked” (unenveloped) virus, he was also determined to identify and begin work then on the simplest enveloped virus. Taking advantage again of the chance, uniquely provided by a sabbatical, to learn and read about new things, he concluded that a particular mammalian virus Sindbiswas the “hydrogen atom” of enveloped viruses he was looking for. Coincidentally, the world’s experts on Sindbis happened to be a husband and wife team at Caltech, James (“Jim”) and Ellen Strauss. Recognizing that an infectious enveloped virus had never been reconstituted from its purified components, he approached the Strausses with his idea of trying to do so, and Jim’s immediate response was “Yes, it’s a slightly crazy idea, but it’s interesting and there’s a (small)
odds, and perhaps with the benefit of beginner’s luck, the experiment worked the first (and second and third) time, and the results were published in 2003, confirming beautifully the theoretical predictions of pressures as high as tens of atmospheres, with the details dependent on the length of the genome and the ambient salt concentrations (because capsids are permeable to salt, and the internal stress is dominated by DNA self-repulsion). The appearance of the 2003 PNAS paper marks a turning point in Bill’s research career. With three exceptions, every paper of his in the nearly 15 years since has dealt with some aspect of “physical virology”, and most of the work has been experimental. The switch from physical chemistry theory to biological experiment required the setting up of a biochemistry lab in space previously employed for studies of Langmuir monolayers−a “cold-turkey” break with the past and a concerted effort to learn the language, techniques, concepts, and challenges of a totally new field. Like Alex, Bill and Chuck participated in the intensive summer molecular biology bootcamp in order to learn some of the fundamental methods, and they committed to building up an experimental group to study viruses from a physical point of view. Generous biochemistry colleagues offered hand-me-down equipment and patient instruction. Most importantly, an intrepid and lively cadre of students and postdocs with lab expertise far exceeding that of their advisers made it possible to meet the challenges of experimental virology. What are the hallmarks of this research? Why is it “physical virology” and not simply “virology”? For one thing, the questions being asked are often in direct response to theory, and Bill has maintained a small but crucial theoretical component in his work, in collaboration with Avi Ben-Shaul. Three theory students in successionAron Yoffe (2002− 2009), Li Tai Fang (2004−2011), and Walter Singaram (2010−2016)have each spent several extended periods with Avi in Israel, providing the conceptual groundwork for the design of new experiments on the physical properties of viruses and their genomes. Rather than focusing on a particular virus in great detail, Bill’s research program has consistently aimed at understanding general principles that apply to a broad range of viruses, as, for example, in his studies of viral assembly. The tools of research have not been restricted to any particular set of biochemical or physical techniques but have been chosen as needed to arrive at answers to qualitative questions by the simplest means possible. For example, Bill and Robijn Bruinsma and Joe Rudnick set out in 2003 with postdocs Roya Zandi and David Reguera to understand the remarkable fact that the majority of viral capsids have icosahedral symmetry. They did so by introducing the simplest relevant model of interacting components, namely, Lennard-Jones particles confined to the surface of a sphere. Crick and Watson (1956) and Caspar and Klug (1962) had shown more than 50 years earlier that icosahedral symmetry would allow for the minimum number of inequivalent positions for capsid protein subunits, implicitly implying a minimum energy configuration. From Monte Carlo simulation of increasing numbers of Lennard-Jones particles on a sphere, Bill and his colleagues demonstrated explicitly in 2004 that particular “magic numbers” of particles with icosahedrally symmetric configurations gave free energy minima consistent with the Caspar−Klug hierarchy of T-number structures. Similarly, their paper one year earlier had established a general analogy between the self-assembly of viral capsidsas a 5792
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John Simon Guggenheim Fellowship (1998), and the Hildebrand Prize of the American Chemical Society (2001). He has presented endowed lectures throughout the States and Europe, including the Brotherton Lectures (University of Leeds, 1988), the Rothschild Lectures (Institut Curie, 1999), the Bikerman Lecture (Case Western Reserve University, 2002), the Laughlin Lectures (Cornell, 2006), the Buhl Lecture (Carnegie Mellon Univeristy, 2010), and the Kaufman Lectures (University of Pittsburgh, 2012), and has been elected a Fellow of the American Physical Society (1987) and of the American Academy of Arts and Sciences (2009). His teaching has been recognized by the UCLA Distinguished Teaching Award in 1996. Reflecting the breadth and impact of his research interests, his invited talks at Gordon Research Conferences span the scientific spectrum including Molecular Relaxation Processes, Theoretical Chemistry, Liquid Crystals, Aqueous Solutions, Liquids, Nanoparticles, Condensed Matter Physics, Polyelectrolytes, and Physial Virology. Similarly, his papers have been published in a comparably broad range of journals including the Journal of Chemical Physics, Molecular Physics, Physical Review, Molecular Crystals/Liquid Crystals, Journal of Statistical Physics, Journal of Colloid and Interface Science, Proceedings of the National Academy of Science, Langmuir, Physical Review Letters, Angewandte Chemie, Biophysical Journal, Science, Nature Materials, Macromolecules, Journal of the American Chemical Society, Virology, ACS Nano, Nucleic Acids Research, Journal of Virology, RNA, PLoS ONE, and the Journal of Molecular Biology. His influence on the many fields he has encountered during his journey from gas-phase spectroscopy to viruses stretches far beyond his important scientific contributions. He has infected not only those who have worked with him directly, but also countless innocent bystanders, with his joyous and open embrace of good science in all its manifestations.
chance of it working”. (Bill took this as strong encouragement.) More importantly still, Jim offered bench space, equipment and reagents, and his and Ellen’s help in training a research student. Benefiting from this generosity and expertise, UCLA Ph.D. candidate Odisse Azizgolshani spent two years in the Strauss lab learning from scratch about how to work with mammalian viruses in cell culture, and attempting a wide variety of ingenious but ultimately unsuccessful efforts to reconstitute infectious Sindbis from its purified RNA genome, capsid and membrane proteins, and phospholipids. She continued this work back at UCLA from 2006 through 2011, in Arnie Berk’s lab, who generously hosted her throughout the completion of her Ph.D. work, because Bill and Chuck did not yet have cell culture facilities or Biosafety Level 2 clearance in their lab. During the years from 2004 onward, experimental programs were put in place to study simple naked (CCMV) and enveloped (Sindbis) RNA viruses, andwith the exception of very recent work by Ph.D. student Yan (Cathy) Jin on the ejection of internal proteins and the effects of polyvalent cations on the pressure of bacteriophagesthe direction of Bill and Chuck’s work shifted from DNA to RNA viruses. In particular, an additional theoretical collaboration with Avi BenShaul was begun, focusing on the unique polymer properties of single-stranded RNAin particular, the nature and consequences of the “effective branching” of long RNA molecules, and the ways in which it is most useful to consider them as “statistical objects”. The successive Ph.D. theses of Aron Yoffe, Li Tai Fang, and Walter Singaram were devoted to establishing the manner and extent to which viral genome RNA sequences give rise to significantly more compact ensembles of secondary structure than nonviral sequences, to the scaling behavior of RNA size with molecular weight, and to the effects of RNA branching on the binding of capsid protein. These theory results were the bases for both the design and the analyses of an extended series of experiments in which postdoc Ajaykumar (“Ajay”) Gopal generated the first systematic datafrom a succession of small-angle synchrotron X-ray, fluorescence correlation spectroscopy, and cryo-electron microscopy investigationsestablishing the differences in size between viral and nonviral RNA sequences of the same length. In parallel, increasing effort in Bill and Chuck’s group was devoted to the in vitro self-assembly of virus-like particles in which the relative packaging efficienciesand the limits of packageable lengthswere being investigated for a wide range of RNA sequences and lengths. This work has been carried out over several years now in the able hands of Ruben CadenaNava, Mauricio Comas-Garcia, Rees Garmann, Christian Beren, and Rich Sportsman. Most recently, Adam Biddlecome, Devin Brandt, and Jerrell Tisnado have begun work on the synthesis and packaging of a variety of RNA “replicons”directly translated molecules one of whose genes codes for the enzyme that replicates them, and the other for a gene whose protein product is to be expressed in high copy number in targeted cells. The group is now self-sufficient as far as all relevant molecular biology and cell culture work are concerned, and is beginning to collaborate directly with groups using animal models. The journey from isolated small molecules in the gas phase, to complex fluids, and now to infectious viruses, has come a long way. Bill’s work has been recognized by many awards and prizes, including an Alfred P. Sloan Fellowship (1974), the Camille and Henry Dreyfus Teacher-Scholar Award (1976), the Lennard-Jones Medal of the British Royal Society (1991), a
Avinoam Ben-Shaul Charles M. Knobler Andrea J. Liu
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