Conference: Cell Decision Making Workshop, Arlington VA, June 10-11, 2013. Cells from across the biological kingdoms are continuously engaged in the process of decision making, by which is meant that cells take information from their surroundings (including neighboring cells), process this data through complex signal transduction and genetic circuits, and modulate their cellular phenotypes in response. Decision making implies that choices are made from competing options and that once made, these choices have some degree of persistence even as conditions change. This workshop will bring together theoretical and experimental scientists to discuss major issues in cell decision-making processes and the new approaches that may be employed to study these issues. This workshop will serve to catalyze discussions between research scientists with shared interests, but working on very different cell systems (eukaryotic vs. prokaryotic). Broader impacts. The workshop will point the direction to new research partnerships between theorists and experimentalists, and help develop a consensus for this field of research driven by the similarities in the biology of diverse cellular systems. The workshop organizers will write a report summarizing the status of the field, including the limits to current understanding; identification of the key questions for future research efforts; and the barriers to be overcome as the field moves forwards. The workshop supports the goal of broadening participation by the inclusion of women and members of groups under-represented in science. This award is supported by all clusters in the Division of Molecular and Cellular Biosciences and by the Physics of Living Systems Program in the Division of Physics.
At the request of the NSF, the Center for Theoretical Biological Physics at Rice University convened a two-day meeting in Arlington, VA to discuss the emerging interdisciplinary field of cellular-decision making (CDM). This research area, to be defined more precisely below, spans different directorates at the NSF and hence we were happy to have the sponsorship and active participation of program managers from both bioscience and math/physical science. In this report, we present a synopsis of these discussions and on the consensus reached as to prospects and needs for accelerating progress in this extremely exciting topic. It is worth noting that the participants cooperated in creating many animated exchanges that truly helped clarify the state of the field. This occurred because all of us felt (and were reinforced in this feeling) that this field is at the cutting-edge of modern science and progress on the questions explored in this meeting would be of tremendous import to everyone interested in making biology more quantitative and predictive. Thus, it is easy to argue that the NSF should be encouraged to invest resources towards accelerating this progress. It has become clear in recent years that biological cells act as sophisticated information processing entities, transforming sensory data regarding both their surroundings and their internal state into behavioral actions. When there is a non-trivial repertoire of such actions available, it has become commonplace to refer the overall process as the making of a cellular "decision". It was noted that the physical science community does not describe a magnet as "deciding" which way to polarize when its temperature is lowered; yet, we are comfortable with this language in biological systems, even for the simplest case of a viral choice between lysis (killing the host) and lysogeny (becoming incorporated into the host genome). It appears that the notion has the process has been shaped by evolution to be (at least partially) of adaptive utility as a response to inferences made from the sensory data has shaped our conceptual perspective. What are the significant roadblocks to rapid progress? Connected to this is the more pragmatic question of, what should the funding priorities be so as to accelerate progress? Here there were several useful lines of thought. Most of the field has focused on genetic degrees of freedom and chemical signals responsible for their control. For many important cases, mechanical degrees of freedom and intercellular forces play an equally critical role. We need to develop methods to measure these factors in in vivo settings, as well as modeling approaches that couple biomechanics to signal transduction and to genetics. We need to continue to emphasize a mix of systems. It was recognized that fundamental progress and ideas are usually easier to identify in simple contexts, but also that it is not always obvious how to generalize from microbes to metazoans. Perceived barriers between molecular versus cellular biology (and biological physics) and between evolutionary changes to genomes versus phenotypic adaptation, were in some cases impeding progress. Unlike the neat separation between, for example, particle physics and condensed-matter physics, there is no reason to expect in general that cellular networks are protected from the conformational degrees of freedom of their components. Also, evolutionary arguments can help us understand circuitry, and conversely cellular decision-making networks can definitely extend to choices regarding mutations and recombination. It was very clear from the presentations that the barriers between physical and biological sciences were being overcome on a regular basis by researchers in the field. An excellent example of this was provided by the talk on quorum sensing in Pseudomonas. Unlike what would have been the case one or two decades ago, many of the projects combined excellent biology with quantitative measurements (often with the help of carefully engineered devices) and with sophisticated theoretical analyses. Future work in this field will certainly benefit from continued collaborations among all the disciplines interested in the fundamental questions at the heart of CDM and interdisciplinarity in approach should be a hallmark of NSF support for this area. In summary, thinking about CDM helps us organize our ideas about what truly distinguishes living matter. It brings to the fore issues of evolution of function, optimality and robustness of design, and communication-based cooperativity. The participants all left the meeting in a state of excitement, pledging to redouble their efforts to answer the challenges posed therein.
