Bioactive Systems Symposium

On June 12, 2008, Polytechnic University in conjunction with the New York Academy of Sciences will host a day-long symposium that highlights cutting-edge research on Bioactive Systems. It will highlight the recent advances in molecular design, self-assembly, gene circuit, artificial cell design, and evolution with applications in biology, medicine, environment, and energy. The symposium will be highly interdisciplinary and will bring together recognized scientists and engineers who are performing research in bioactive systems with core knowledge in the physical sciences and engineering. A poster session at the symposium will provide individuals the opportunity to present their research and interact with the attendees of the symposium.

Symposium Schedule

• 8:30-9:00
  Registration Check-In, Set up Posters


• 9:00-9:10
  Welcome and Introduction


• 9:10-9:55
  Mechanics of Signal Transduction in Cell Membranes
  Jay Groves, Department of Chemistry, UC Berkeley


• 9:55-10:40
  Spider Silk: An Ancient Biomaterial for the Future
  Randy Lewis, Department of Molecular Biology, University of Wyoming

• 10:40-11:00
  Refreshments and Poster Viewing


• 11:00-11:45
  Appreciating the Designs of the Blind Watchmaker: How Characterization and Creation are Creating a New Biological Engineering Science
  Adam Arkin, Department of Bioengineering and Chemistry, UC Berkeley


• 11:45-12:30
  Metabolic Engineering and Systems Biology for Energy
  James Liao, Department of Chemical and Biomolecular Engineering, UCLA


• 12:30-2:00
  Lunch Break and Poster Session


• 2:00-2:45
  Combinatorial Code for Epithelial Patterning by Signaling Pathways
  Stanislav Shvartsman, Department of Chemical Engineering, Princeton University


• 2:45-3:30
  Coarse-Grained Analysis of Collective Motion
  Jeffrey Moehlis, Department of Mechanical Engineering, UC Santa Barbara


• 3:30-3:50
  Refreshments and Poster Viewing


• 3:50-4:35
  Computational Protein Design: Theory, Experiments, Applications
  Homme Hellinga, Department of Biochemistry, Duke University Medical Center


• 4:35-4:45
  Closing Remarks


• 4:45
  Reception

Abstracts

Mechanics of Signal Transduction in Cell Membranes
Jay Groves, UC Berkeley

Signal transduction in living cells is carried out through cascades of chemical reactions, which generally begin on the cell membrane surface. In recent years, there has been growing realization that the large-scale spatial arrangement of cell surface receptors can regulate the outcome of ensuing signal transduction process. Signaling through the T cell receptor (TCR) in the context of the immunological synapse provides a case in point. Spatial reorganization of TCRs occurs on multiple length-scales, and apparently with multiple purposes, during antigen recognition by T cells. The cell membrane and cytoskelton, working as an inseparable unit in this case, create the mechanical framework within which TCR signaling processes occur. To better study these phenomena, a new experimental strategy, in which the spatial positions of cell membrane receptors are directly manipulated through mechanical means, has emerged. By physically inducing a 'spatial mutation' of the signaling apparatus, the role of spatial organization in signal transduction as well as the mechanisms by which it arises can be illuminated. Specific applications of this strategy to TCR signaling will be discussed.

Spider Silk: An Ancient Biomaterial for the Future
Randy Lewis, University of Wyoming

Spiders have been using protein-based nanomaterials, which self-assemble into fibers and sheets, for over 450 million years. Spider silk is the strongest natural fiber known. Spider silks have the potential to provide new bio-based materials for numerous applications ranging from protective clothing to medical products to composite materials. We have cloned number of spider silk genes and their sequences revealed the basis for understanding the key elements of spider silk proteins relative to their materials performance. Based on that information we have created recombinant proteins designed to have properties differing from those of natural silks.

Appreciating the Designs of the Blind Watchmaker: How Characterization and Creation are Creating a New Biological Engineering Science
Adam Arkin, UC Berkeley

There is a philosophical danger in using the language of engineering to describe the patterns and operations of the evident products of natural selection. Invoking principles of design runs the risk of invoking a designer. But as we analyze the increasing amount of data on the genome and its organization across a wide array of organisms we are discovering there are patterns and dynamics reminiscent of designs that we, as imperfect human designers, recognize as serving an engineering purpose including the purpose to be designable, or rather, evolvable. There is no doubt that biological artifacts are the product of Dawkin's Blind Watchmaker, natural selection. But natural selection has at its heart one of engineering's most prized principles, optimization. The Survival of the Fittest principle, while not directly specifying an objective function that an organism must meet, nonetheless provides a clear figure of merit for long term biological success, reproduction, and is a well-formed if ever changing specification.The Survival-of-the-Fittest objective function has many features that we might think would lead to recognizable engineering solutions. Organisms must sense the environment and transfer these signals through controllers which operate actuators that make the organism behave: forage for food, choose the best food sources, deploy predations, defend themselves, hide, mate and more in order to survive. There are physical constraints on how solutions can be implemented given the environment and the composition of the life form. System biologists are now maturing in their ability to uses these ideas to begin to explore the engineering features of natural systems: their control, stability, filtering, coding capacity, information transfer characteristics, modularity, and perhaps most different in biological systems their evolvability. Synthetic biologists are picking up these topics for use in designing new behaviors in cells and bring other engineering challenges to the table such as automation of cloning, and more. This marriage of systems characterization and applications design is creating a new biological engineering science. I will outline the success and challenges of this engineering type of systems biology in understanding the form and function of organisms that are in the process of being harnessed for therapeutic applications: lentiviral treatments for HIV and bacterial treatments for cancer.

Metabolic Engineering and Systems Biology for Energy
James C. Liao, UCLA

Natural metabolic circuits are evolved for the organisms' survival and fitness in natural environments. However, to harness organisms' capability for a human application or to intervene a pathological process may require man-made metabolic circuits that interact with existing intracellular networks. In the past few years, synthetic biological circuits have been studied to pave the way for applications useful to mankind. In this talk, we will demonstrate how cellular metabolic network can be reengineered to achieve a desired purpose. In particular, we will discuss general design approaches to engineer cellular metabolic networks. Guided by mathematical analyses, we have re-wired the metabolic circuits for production of specific biochemicals; we have constructed a synthetic feedback control system for redirecting metabolic flux; and we have demonstrated a gene-metabolic oscillator that mimics a key feature in circadian rhythm, namely the coupling between metabolism and gene expression oscillation. In addition, we rewired the metabolic network to produce higher alcohols (C3 to C5), which enables the exploration of these rare alcohols as biofuels.

Combinatorial Code for Epithelial Patterning by Signaling Pathways
Stanislav Shvartsman, Princeton University

Regulated deformations and folding of epithelial layers give rise to three-dimensional organs, a process that relies on patterning of cell fates by signaling pathways. Previous studies of epithelial morphogenesis focused on single genes and small networks, but the overall diversity and dynamics of patterns in any given system have not been characterized. We provide a systems-level analysis of epithelial patterning in /Drosophila/ egg development. We establish and test experimentally a formal description of patterns for dozens of genes in the epithelium that gives rise to the three-dimensional eggshell. We demonstrate that >200 expression patterns in this system can be represented using a code based on six basic shapes and three operations.

We show how our annotation enables a statistical characterization of patterning events leading to eggshell morphogenesis and argue that a similar approach is applicable to a wide range of developmental systems.

Coarse-Grained Analysis of Collective Motion
Jeffrey Moehlis, UC Santa Barbara

We apply the "equation-free" coarse-grained computational framework to understand the population-level behavior for a model for schooling fish. In particular, we focus on a case for which the model can give co-existing stable stationary and mobile collective behaviors. Stochastic effects cause the school to switch between these behaviors, leading to stick-slip dynamics which can be characterized using an effective potential in terms of a population-level coarse variable. The effective potentials found using equation-free techniques compare very favorably with those obtained (with much more computational effort) from long-time simulations.

Computational Protein Design: Theory, Experiments, Applications
Homme Hellinga, Duke University Medical Center

In a computational design experiment the three-dimensional structure of a protein backbone is used to predict mutations that alter properties such as ligand binding, which are then tested experimentally. I will present examples of this approach in the area of receptor design and the redesign of enzyme specificity. Recently we have developed experimental automation methods that enable us to evaluate relatively large numbers of designs in the laboratory. It is clear that the combination of computational design and experimental automation will allow us to systematically explore the molecular recognition principles encoded in the computational methods.