"Engineering cell fates in vitro"
"Engineering cell fates in vitro"
"Programming Genomes to Expand Life's Functional Repertoire"
Farren Isaacs is Assistant Professor of Molecular, Cellular and Developmental Biology and Systems Biology at Yale University. He received a B.S.E in Bioengineering from the University of Pennsylvania and Ph.D. in Biomedical Engineering-Bioinformatics at Boston University, where he pioneered the development of synthetic RNA molecules capable of probing and programming cellular function. As a research fellow in genetics at Harvard, he invented enabling technologies for genome engineering. His research is focused on finding ways to construct new genetic codes and reprogrammable cells that serve as factories for chemical, drug and biofuel production. He has been named a “rising young star of science” by Genome Technology Magazine, a Beckman Young Investigator by the Arnold and Mabel Beckman Foundation and recipient of a Young Professor award from DuPont.
Dr. Clare M. Waterman, Ph.D.
NIH Distinguished Investigator Laboratory of Cell and Tissue Morphodynamic
Integration of actin dynamics and cell adhesion by a three-dimensional, mechanosensative molecular clutch
Forces generated in the actin cytoskeleton are transmitted across transmembrane receptors to the extracellular matrix (ECM) or other cells during directed migration. Force transmission from the cytoskeleton to the receptors is mediated by a series of mechanosensitive regulatable, indirect protein-protein interactions termed the “molecular clutch.” In integrin-based focal adhesions, the proteins making up this linkage are organized into a conserved threedimensional nano-architecture. Molecular clutches of similar architecture likely mediate cell adhesive interactions during tissue morphogenesis, the immune response, and vascular function.
Rudolf Jaenisch, M.D. Professor of Biology, MIT and White Head Institute - Founding Member
iPS Cell Technology, Gene Editing and Disease Reseach
The recent demonstration of in vitro reprogramming using transduction of four transcription factors by Yamanaka and colleagues represents a major advance in the field. However, major questions regarding the mechanism of in vitro reprogramming need to be understood and will be one focus of the talk. A major impediment in realizing the potential of ES and iPS cells to study human diseases is the inefficiency of gene targeting. Methods based on Zn finger or TALEN mediated genome editing have allowed us to overcome the inefficiency of homologous recombination in human pluripotent cells. Using these genome editing approaches we have established efficient protocols to target expressed and silent genes in human ES and iPS cells. The most recent advance comes from the use of the CRISPR/ Cas9 system to engineer ES cells and mice. This technology allows the simultaneous editing of multiple genes and will facilitate establishing relevant models to study human disease. We have used this technology to generate isogenic pairs of cells that differ exclusively at a disease causing mutation. The talk will describe the use of isogenic pairs of mutant and control iPS cells to establish in vitro systems for the study of diseases such as Parkinson’s and Rett syndrome.
The costs and consequences of biological control
Arthur D. Lander, M.D., Ph.D.
Center for Complex Biological Systems, and Departments of Developmental & Cell Biology and Biomedical Engineering, University of California, Irvine, CA
After a century of great strides in identifying the components and mechanisms out of which living things are constructed, biologists are increasingly turning (or returning) to questions of biological organization: Why are biological systems built the way they are? What explains the presence of the detailed mechanisms and patterns we observe? How much is chance, and how much is necessity? A defining feature of the recent Systems Biology movement is the tendency to explain biological organization in terms of design principles, i.e. strategies for achieving ends dictated by natural selection. Following this approach I will discuss two examples of how selection for the ability to perform diverse tasks imposes constraints on biology, constraints that justify the need for complex patterns of organization that might otherwise seem arbitrary. In one case I will talk about systems that implement robust pattern formation during animal development. In the other I will talk about stem cell systems, which underlie the development and/or maintenance of most tissues and organs, and which provide the context within which cancers arise. In both cases, I will argue that approaching biology as a set of solutions to control problems provides more satisfying answers than are obtained by treating it as merely a complicated example of physics.
Professor Viola Vogel
Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zürich, Switzerland
How Cells and Bacteria Exploit Proteins as Mechano-Chemical Signaling Switches
The physical and biochemical properties of extracellular matrix and of synthetic materials provide critical cues to cells, from mechano-regulated bacterial adhesion to angiogenesis, and finally to the differentiation of stem cells. It is thus of major importance to gain mechanistic insights into how mechanical stretching of extracellular matrix molecules can alter various cell functions. While investigating these three distinct physiological processes, common motifs are emerging how bacteria and cells take advantage of mechanical forces to regulate the function of proteins by stretching them out of their equilibrium structures. In this context, new assays and techniques were developed that allow probing how the stretching of proteins alters their structure-function relationships. Taken together, new insights into various underpinning mechanotransduction events are emerging how mechanical cues are translated into biochemical signals that ultimately regulate bacterial adhesion and various cellular processes.
Norman Chandler Professor of Cell Biology
California Institute of Technology
Gene network models and logic processing in development
Gene regulatory networks (GRNs) control the dynamic spatial patterns of regulatory gene expression in development. Thus, in principle, GRN models may provide system-level, causal explanations of developmental process. To test this assertion, we have transformed a relatively well-established GRN model into a predictive, dynamic Boolean computational model. This Boolean model computes spatial and temporal gene expression according to the regulatory logic and gene interactions specified in a GRN model for embryonic development in the sea urchin. Additional information input into the model included the progressive embryonic geometry and gene expression kinetics. The resulting model predicted gene expression patterns for a large number of individual regulatory genes each hour up to gastrulation (30 h) in four different spatial domains of the embryo. Direct comparison with experimental observations showed that the model predictively computed these patterns with remarkable spatial and temporal accuracy. In addition, we used this model to carry out in silico perturbations of regulatory functions and of embryonic spatial organization. The model computationally reproduced the altered developmental functions observed experimentally. Two major conclusions are that the starting GRN model contains sufficiently complete regulatory information to permit explanation of a complex developmental process of gene expression solely in terms of genomic regulatory code, and that the Boolean model provides a tool with which to test in silico regulatory circuitry and developmental perturbations.
How Emergence Drives the (Science and) Ethics of Synthetic Biology
Professor of Bioengineering Co-Chair, Department of Bioengineering Investigator, Howard Hughes Medical Institute Stanford University
Precision Measurement in Biology
Is biology a quantitative science like physics? I will discuss the role of precision measurement in both physics and biology, and argue that in fact both fields can be tied together by the use and consequences of precision measurement.
The elementary quanta of biology are twofold: the macromolecule and the cell. Cells are the fundamental unit of life, and macromolecules are the fundamental elements of the cell. I will describe how precision measurements have been used to explore the basic properties of these quanta, and more generally how the quest for higher precision almost inevitably leads to the development of new technologies, which in turn catalyze further scientific discovery. In the 21st century, there are no remaining experimental barriers to biology becoming a truly quantitative and mathematical science.
Dr. L. Benjamin Freund
Adjunct Professor of Materials Science and Engineering, University of Illinois at Urbana-Champaign; H. L. Goddard University Professor Emeritus, Brown University
"Analysis of Cell Adhesion Phenomena as Observed at Different Size Scales"
Abstract: We discuss several phenomena, each concerned with an aspect of adhesion of a cell to its surroundings or to another cell, but which are observed at different size scales. In each case, recently reported laboratory observations provide a framework for quantitative modeling of the underlying phenomenon. At the smallest scale, we consider the separation of specific molecular bonds under the action of externally applied forces (as observed by Evans and co-workers with the bio-membrane force probe, for example) with a view toward characterization of the bond structure and rate sensitivity from separation data. At an intermediate size scale, we consider a physical basis for the maximum spacing between cell/substrate bonding sites common among several cell types (observed by Spatz and co-workers, for example). It is demonstrated that thermal fluctuations alone imply that membrane bonding cannot occur if bond site spacing is beyond some system specific threshold level. Lastly, at the scale of cell interactions within compact clusters of thousands of cells, we consider the forces that come into play as the shape of such a cluster changes spontaneously (as observed by Morgan and co-workers, for example). Recent progress toward development of mathematical models for each of these phenomena is summarized.
Paul Root Wolpe
Director of the Emory Center of Ethics
Ethical Challenges of Stem Cell Research, Synthetic Biology, and Regenerative Medicine
Dr. Robert Langer
MIT Department of Chemical Engineering
"Engineering of Integrated Materials and Cell Based Systems"
I will start by discussing how I - as a chemical engineer - initially got involved in the interface between biology and engineering, which would lead to the isolation of the first angiogenesis inhibitors and the development of controlled release systems for macromolecules. I will then cover the engineering of novel microelectronic systems. Such systems have the ability to sense levels of drugs or other substances in blood. They can also secrete drugs into the bloodstream. Next, the possibility of creating cell based tissues and organs - and the challenges associated with that - will be discussed. Finally, the development of new high-throughput, polymer-based tools that can control the differentiation and growth of stem cells and other cells will be examined.