Day 2 :
Bowling Green State University, USA
Keynote: Signaling from a scaffold
Time : 9:00-9:30
Carol Heckman is an expert on pre-neoplasia and has published over 30 papers on this subject. She developed optical and computational methods for cell feature analysis and has applied these methods to distinguishing the phenotypes of normal and cancer cells.These features are the basis of an assay to flag chemicals of interest for drug development and target drugs to specific diseases. Her current work is on scaffolds through which cells recognize their microenvironment and specifically on the combinatorial aspects of FC composition and dynamics. She is the Director of the Center for Microscopy & Microanalysis at Bowling Green State University.
Cells are attached to their substrate by Focal Contacts (FCs) containing the hetero dimeric transmembrane protein, integrin, which signals through networks of other proteins including Rho-family GTPases and their accessory proteins. Integrins link molecules from the substrate to various adaptors, talin, etc., which bind to actin. Whereas, integrin binding at the exterior signals “downstream” its binding affinity to the substrate can also be altered by regulatory complexes inside the cell.We developed methods of unbiased classification of cell features, which help in understanding “inside-out signaling”. Protrusions were identified by latent factor analysis as factors #4, #5, #7 and #16.FCs in factor #7 protrusions were restricted in their dimensions, indicating qualitative differences in FCdynamics or composition.We discovered that the Cdc42 GTPasehas a role in differentiating the more adhesive side of a cell specifically through factor #4 features.This indicates that cells both sense and respond to their environment through at least the #4 protrusive features. To identify protein-protein interactions that are critical to regulating each protrusion, we use blocking peptides representing the docking sites of candidate regulatory proteins. Two GTPase-binding proteins, the actin-microtubule cross linking IQ-domain protein, IQGAP, and the Cdc42-activated kinase, ACK, were implicated in factor 4 regulation. Likewise the target of phorbol esters, protein kinase C, regulates 4. Recent data suggest that factor #4 protrusions can be affected by proteins that regulate integrin itself and clathrin-mediated endocytosis. Thus, the dynamic, but detectable domains of cells may be established and maintained by differences in FC composition or dynamics.
McMaster University, Canada
Time : 9:30-10:00
Timothy R Field studied undergraduate mathematics at King’s College, Cambridge University, and went on to receive a Doctorate in mathematics from New College and the Mathematical Institute, Oxford University in 1997, where he studied mathematical physics under Sir Roger Penrose. He is an Associate Professor in the Departments of Electrical & Computer Engineering and Mathematics & Statistics at McMaster University. He is fellow of the Institute of Physics and the Institute of Mathematics and its Applications, and twice recipient of NSERC Discovery Awards for research into electromagnetic scattering from random media and related phenomena.
The dynamics of a spin system is usually calculated using the density matrix. However, the usual formulation in terms of the density matrix predicts that the signal will decay to zero, and does not address the issue of individual spin dynamics. Using stochastic calculus, we develop a dynamical theory of spin relaxation, the origins of which lie in the component spin fluctuations. This entails consideration of random pure states for individual protons, and how these pure states are correctly combined. Both the lattice and the spins are treated quantum mechanical. Such treatment incorporates both the processes of spin-spin and (finite temperature) spin-lattice relaxation. Our results reveal the intimate connections between spin noise and conventional spin relaxation. These developments in theoretical aspects of spin noise and relaxation and their interrelationship reveal a modified spin density, distinct from the density matrix, as the necessary object to describe fluctuations in spin systems. These fluctuations are to be viewed as an intrinsic quantum mechanical property of such systems immersed in random magnetic environments and are observed as spin noise in the absence of any radio frequency excitation. With the prospect of ultrafast digitization, the role of spin noise in real-time parameter extraction for spin systems, and the advantage over standard techniques, is of essential importance, especially for systems containing a small number of spins. In this presentation we outline prospects for harnessing the recent dynamical theory in terms of spin-noise measurement, with attention to real-time properties.