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Scialog 2015: Molecules Come to Life

M. Lisa Manning, physics, Syracuse University, makes a point at Scialog 2015: Molecules Come to Life
M. Lisa Manning, physics, Syracuse University, makes a point at Scialog 2015: Molecules Come to Life

Scialog 2015: Molecules Come to Life, the first of two conferences bringing together physicists, biologists and chemists, ended March 15 with 20 new proposals for innovative, fundamental research to probe the mysteries of how cells work.

The interdisciplinary conference is sponsored by the Gordon and Betty Moore Foundation and Research Corporation for Science Advancement. It attracted 65 theoretical and experimental scientists from around the nation.

In accordance with the Scialog paradigm, RCSA Program Director Richard Wiener encouraged the researchers to: engage in authentic dialog in a collegial spirit of cooperation; identify and analyze research barriers and develop approaches for breakthroughs; build a creative cross-disciplinary community that is more likely to produce breakthroughs; and form new collaborations based on ideas that emerge at the conference.

One of the major goals of Scialog is to foster new connections among elite early career scientists. While this is bound to happen at a small conference of ~50 people, Research Corporation and the Gordon and Betty Moore Foundation wanted this year’s conference to explicitly encourage new and stronger connections among Scialog Fellows.

To achieve this goal, the Scialog Advisory Committee, led by Wiener, designed a set of highly interactive activities. Wiener also worked with Datascope, a consulting firm of former Northwestern University data scientists, to develop a technique for strategically connecting previous unacquainted Fellows in “mini” breakout discussions, which were unfacilitated sessions of four people each. Participants reported that many stimulating new interactions occurred in these talks.

In addition, the conference featured multiple breakout sessions with five parallel discussion groups of 10 people each (with two additional senior scientists acting as facilitators for each group).

“We received numerous comments on the stimulating nature of the discussions,” Wiener said. “And we were delighted at the number of innovative proposals the participants were able to develop over the course of several days.”

Gary Greenburg, program officer for the Gordon and Betty Moore Foundation, told the participants at the beginning of the meeting that it should be viewed as an experiment in interdisciplinary and community building among researchers. Near the end of the conference, Greenburg said, “I am declaring the experiment a success.”

The Scialog Advisory Committee immediately began evaluating the 20 proposals resulting from this process, and will decide which ones should be funded in about two months. The Gordon and Betty Moore Foundation and Research Corporation anticipate funding about five proposals.

Committee members include Ken Dill, director of the Louis and Beatrice Laufer Center for Physical and Quantitative Biology at Stony Brook University; Daniel Fisher, professor of applied physics at Stanford University; Martin Gruebele, the James R. Eiszner Professor of Chemistry at the University of Illinois at Urbana-Champaign; Jané Kondev, chair of the Physics and Quantitative Biology Program at Brandeis University; and Boris Shraiman, a permanent member of the Kavli Institute of Theoretical Physics at UC Santa Barbara.

Keynote addresses included:

-- Boris Schraiman’s discussion of how physics-style phenomenological modeling can help to build a bridge of understanding of biological development from subcellular scales to the “organismal” scale. Schraiman, who is particularly interested in the role of interactions in biological systems, discussed one of the main foci of his work, morphogenesis, noting, “A very simple model describing morphogen diffusion and degradation will tell you that morphing profiles are exponential. But the moment you scratch the surface, all sorts of questions arise.”  Questions, he pointed out, regarding fluctuations and reproducibility, scaling and size; these must be answered before researchers can arrive at universal principles that will lead to accurate modeling in various organisms. He observed that “big flies and little flies may have the same morphogen, but it’s not at all clear how scaling works” in each of these organisms. “Recent studies strongly suggest that morphogens are not static,” he noted. “The dynamics of morphogens may be essential.” Fundamentally, Schraiman’s message was that the genetic program of the cell is helped along by cellular interactions to create developmental dynamics. “This is a beautiful and rich field of science,” he said.

-- Jané Kondev reinforced Schraiman’s message by delivering what he termed an “Ode to Phenomenological Models.” He described how his interest in the subject began: “In grad school in 1972 I saw the opinion piece written by Phil Anderson [Princeton Nobel laureate, b 1923], his ode to phenomenological physics. Models were deemed unworthy of theoretical physicists for a long time, but the key idea in this paper is that if I’m looking at a glass of water, it’s silly to look at individual molecules -- It’s detrimental to the advancement of science to look at molecules if I’m studying the flow of water. If you think about that variable of flow, we can write down equations addressing density and velocity. Phil emphasizes these equations are as fundamental as equations of quantum mechanics.”  Kondev proceeded to give a string of examples demonstrating how genes and other factors control material parameters, concluding, “The larger point being, once we have these coarse grain models we have something to argue about,” meaning phenomenological models are predictive.  “I’ve been going blue in the face trying to explain phenomenological models are as important as molecular models,” Kondev said.

-- Daniel Fisher changed the title of his talk from “Evolution and Modeling Cell Biology” to “What Could Evolutionary Cell Biology Be?” and proceeded to delve into questions about how evolution changes functions and how new functions evolve, with the fundamental question being whether there are useful general principles to be derived from such processes. Most of his discussion was focused on the nature of evolution in “temporarily periodic environments,” that is, oscillations in various biological functions. He touched on Rainey’s work on Pseudomonas fluorescens’ selection for a changed phenotype, and Murray’s work on diurnal oscillations in the budding yeast Saccharomyces cerevisiae. He also discussed the circadian rhythm affecting the complicated molecular basis of phosphorylation in the blue-green algae Synechococcus elongates.  “Can these [phenomena] be understood mechanistically, in terms of the modular organization of cell biology?” Fisher asked. “Or instead should we consider these are consequences of complex networks with a huge number of possible ways to evolve from old and new accidental interactions?” A more fundamental question, he noted, is whether evolution can serve as a useful Ockham’s razor for understanding and modeling the functions of cells.

In addition, over two days of the three-day conference, a dozen early career Scialog Fellows presented 15-minute talks on their areas of research.

“One of Scialog’s goals is to encourage collaborations between theorists and experimentalists. Another is to encourage approaches that are testable by experiments,” said RCSA President Robert Shelton. “It appears from the proposals developed at the first Molecules Come to Life conference that we’re succeeding. We look forward to the second meeting in March 2016, when first-round award recipients will be reporting on the initial results of their research and all Scialog Fellows will be encouraged to compete for the next round of funding.” 

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