Thursday, June 14, 2012 - 1:00pm
"Emergent Length Scales in Patterning of Cellular Lattices"
The main focus of our work is on the quantitative analysis of development. Our goal is to establish models that connect multiple levels of description, from gene sequence to pattern formation and morphogenesis. We emphasize close coupling between genetic experiments, computations, and theory, and use the fruit fly as an experimental system for model validation. Current projects include genome-wide studies of signaling in the Drosophila ovary, parameter estimation for morphogen gradients, and quantitative analysis of feedback control in pattern formation.
Wednesday, May 23, 2012 - 4:00pm to 5:00pm
"Control of in vivo Developmental Pattern Formation via a New Large-scale Optogenetic Workstation: Opportunities for Bioengineering, Synthetic Biology, and Regenerative Medicine"
The capacity to generate a complex organism from the single cell of a fertilized egg is one of the most amazing qualities of multicellular animals. The processes involved in laying out a basic body plan and defining the structures that will ultimately be formed depend upon a constant flow of information between cells and tissues. The Levin laboratory studies the molecular mechanisms cells use to communicate with one another in the 4-dimensional dynamical system known as the developing embryo. Through experimental approaches and mathematical modeling, we examine the processes governing large-scale pattern formation and biological information storage during animal embryogenesis. Our investigations are directed toward understanding the mechanisms of signaling between cells and tissues that allows a biological system to reliably generate and maintain a complex morphology. We study these processes in the context of embryonic development and regeneration, with a particular focus on the biophysics of cell behavior. In contrast to other groups focusing on gene expression networks and biochemical signaling factors, we are pursuing, at a molecular level, the roles of endogenous voltages, pH gradients, and ion fluxes as epigenetic carriers of morphological information. Using gain- and loss of- function techniques to specifically modulate cells' ion flow we have the ability to regulate large-scale morphogenetic events relevant to limb formation, eye induction, etc. We believe this information will result in important clinical advances through harnessing the biophysical controls of cell behavior.
Wednesday, December 14, 2011 - 12:00pm
"Understanding the Vulnerability of the Developing Human Neural System: A Stem Cell Approach"
There is overwhelming evidence that environmental factors play a role in the development and progression of a host of central nervous system disorders. It is likely that many of these effects are due to insults and exposures that occur during development. Data from human exposures reveal critical windows of susceptibility (WOS) during neural development. Unfortunately, animal models fail to faithfully recapitulate these vulnerable windows creating a need for appropriate human-based model systems. We are focusing on three specific windows of neurulation susceptibility: 1) starting with human embryonic stem cells (preneurulation stage) extending to what is believed to be the first definable early in vitro neurulation stage, neural rosette formation. 2) neural rosette to neuroepithelial cell (neural tube) and 3) neural tube neuroepithelial cell to early neuronal cell differentiation. Previously we have demonstrated that using unique culture conditions in vitro sourced and uniformly generated cells corresponding to these stages were derived from human ES cells and staged cells are cryopreservable to facilitate the study of WOS during neurulation. Furthermore, the experimental paradigms could provide the foundation for additional studies that could influence FDA and EPA regulatory decision-making.
Friday, May 6, 2011 - 9:00am
"BioMEMS and Biofabrication for Development of Cellular Systems"
Development of cellular systems and biological machines will require technologies for the characterization, manipulation, and arrangement of cells. Microfabrication-inspired approaches can play an important role towards achieving these goals. In this talk, we will present an overview of our work relevant to the NSF STC (Emergent Behavior of Integrated Cellular Systems). We will summarize our recent developments using micro-mechanical sensors for characterization of mass and growth of single adherent cells, 2- and 3-D patterning of cells (fibroblasts, muscle, and neurons) for applications in angiogenesis and tissue engineering, and fabrication of hybrid cell-polymer structures as building blocks for biological machines.
Friday, April 1, 2011 - 2:45pm
"Molecular Imaging Probes for Biological and Disease Studies"
In this talk, I will present the development of molecular imaging probes in my lab, including molecular beacons, quantum-dot fluorescent protein FRET probes and nanoparticle based contrast agents for fluorescence imaging in living cells and MR imaging in animals. Examples will be given to illustrate the application of these probes in biological and disease studies, including detection of stem cells, intracellular pH sensing, enzymatic activity assay, and tumor imaging. Potential applications in the development of cellular machines will be discussed.
Friday, March 4, 2011 - 4:00pm
"Creating 3D Microvascular Networks in vitro"
Cell populations exhibit various types of emergent behaviors, even in a homogeneous cell population. Our studies are aimed at understanding how emergent properties arise, and how they might be controlled. Present studies focus on the formation of vascular networks in vitro. Microfluidic systems have been created that permit the study of vascular sprouting under the action of gradients in growth factors or pressure. New results demonstrate that (1) transendothelial flow can act as an angiogenic “switch,” regulating vascular sprouting, (2) that functional vascular networks can be formed bridging across gel regions approximately 1 mm wide, and (3) that these networks can be regulated by variations in matrix stiffness and by “feeder cells” suspended in alginate beads. These studies have important implications to tumor angiogenesis and biological machines that require a vascular supply.