Volume 15 Number 2	March 1999

Scientific Simulations Gas Phase Nucleation Multi-Component/ Multi-Phase Materials Estimating Hospital Quality Future Symposium Colloquium Series Special Seminars Visitors Supercomputing '98 Research Reports A Biological Problem Viewed Through the Lens of Mathematics: Pattern Formation and Morphogenesis in Early Development Professor Hans G. Othmer Department of Mathematics University of Utah Salt Lake City, Utah How does the zebra get its stripes and the leopard its spots? Why do we have five digits on our hands and how do they come to be arranged properly? These are questions of how pattern is formed in early development, questions that have fascinated experimentalists and theoreticians for at least a hundred years. Molecular biologists have made enormous strides in understanding the signals that control gene expression, but how are the signals controlled? How do cells in a developing system ‘know' where they should go and what they should do when they get there? In this seminar, Professor Othmer showed how mathematical models and computational experiments using these models shed light on some of these questions. Professor Othmer discussed two major aspects of pattern formation and morphogenesis. The first dealt with how cells integrate the signals they detect, how they move in response to these signals, and how the microscopic behavior of individuals can be incorporated into macroscopic continuum descriptions of cell populations. A reinforced random walk and continuum limits were discussed, and Professor Othmer showed how a velocity-jump stochastic process leads to a Boltzmann-like transport equation. He went on to show how classical chemotaxis equations are obtained from this process. The second aspect dealt with the interaction of growth and pattern in a developing system. A model for vertebrate limb formation based on a fluid mechanical description of tissue was discussed, and a numerical method for treating the free boundary problem that arises in the model was demonstrated. This model can provide experimentalists with new insights into the interaction between growth, cell-cell signaling, and pattern formation in the developing limb. Crumpling a Rope: From Chain Collapse Phase Transition to Protein Folding and DNA Knots Professor Alexander Yulij Grosberg Department of Physics and Center for Materials Science and Engineering Massachusetts Institute of Technology Cambridge, Massachusetts Major biopolymers of DNA, RNA, and proteins function in the living cell in the form of compact condensed globules. From the perspective of physics, polymer condensation, or coil-globule transition, is one of the most fundamental phenomena in polymers. For simple polymers, thermodynamics of transition is well understood, but kinetics remains a challenge. For biopolymers, since they carry biologically important information, dramatically new phenomena arise. In the case of DNA, topology of knots presents a challenge for theoretical understanding. In the case of proteins, quenched but not random sequence of monomers controls thermodynamics and kinetics of reliable folding into a unique spatial structure. This field is experiencing a very fast development. In this seminar, the review of basic concepts was complemented by a discussion of some recent achievements. Statistical Mechanics Methodology for Treating Flexibility in Peptides and Proteins Professor Hagai Meirovitch Supercomputer Computations Research Institute Florida State University Tallahassee, Florida Conformational flexibility plays an important role in protein-protein and protein-ligand recognition. However, analysis of nuclear magnetic resonance (NMR) and X-ray data of flexible peptides and segments of proteins is difficult. A new methodology has been developed for treating flexibility based on statistical mechanics consideration; it includes new techniques for conformational search, methods for calculating the entropy and the free energy, and a novel way to parameterize solvation models. This methodology was described in Professor Meirovitch's seminar, and its potential application to problems in structural biology, drug design, and the genome project was also discussed. Professor Benoit Roux (center) with Professor Oriol Valls (left) of the School of Physics and Astronomy and Professor Darrin York (right) of the Department of Chemistry at the University of Minnesota at a lunch prior to Professor Roux's talk. The Environment of Biomolecules: Atomic and Mean-Field Models Professor Benoit Roux Departments of Physics and Chemistry University of Montreal Montreal, Canada The activity of proteins and enzymes is largely influenced by the properties of the very complex environments in which they have to function. Soluble proteins function in bulk aqueous solutions. In contrast, membrane proteins function in a partly ordered, partly disordered, liquid crystalline bilayer of phospholipids. Bulk solutions, membranes, and detergent micelles are all different environments whose properties must be well-characterized at the microscopic level in order to fully understand the function of biomolecules. Computer simulations based on atomic models in which a large number of molecules are treated explicitly represent one of the most detailed approaches to studying the structure and dynamics of biological systems. Nevertheless, a significant computational cost is associated with the large number of molecules required to construct a valid microscopic model of membrane-protein systems. Furthermore, computer simulations are not exempt from serious problems. For example, particular difficulties are encountered in calculating important quantities associated with membrane functions such as the Nernst membrane potential due to the large statistical errors. Partly because of these problems, it is desirable to develop different approaches in which the influence of the membrane is incorporated implicitly. Recent developments and applications of molecular dynamics simulations, continuum electrostatics, statistical mechanical integral equations, and mean-field models were described in Professor Roux's talk. Dr. Paul Schrater (left) of the Psychology Department at the University of Minnesota, Professor David Heeger (center) of the Psychology Department at Stanford University, and host Professor Daniel Kersten (right) of the Psychology Department at the University of Minnesota talk prior to Professor Heeger's seminar. Linking Human Brain Activity with Perceptual Performance using Functional Magnetic Resonance Imaging Professor David Heeger Department of Psychology Stanford University Stanford, California The main focus of research in Professor David Heeger's laboratory is the use of functional magnetic resonance imaging (fMRI) to quantitatively investigate the relationship between brain and behavior. In this seminar, Professor Heeger presented results from three separate studies. In the first study presented, perceptual studies suggested that visual motion perception was mediated by opponent mechanisms believed to correspond to mutually suppressive populations of neurons sensitive to motions in opposite directions. Strong motion opponency was found in a secondary visual cortical area known as the human MT complex (MT+). These results provided the clearest evidence to date that direction selective signals underly human MT+ responses, and neuronal signals in human MT+ support visual motion perception. In the second study, Professor Heeger tested whether brain activity in primary visual cortex (V1) might be modulated by attention. In the experiments, subjects fixated the center of a display while performing a visual discrimination task on either the right or the left (without moving their eyes). Stimuli on the right were processed by neurons in the left hemisphere and vice versa. The results clearly demonstrated that V1 neural activity could be modulated by attention; activity modulated out of phase in the two hemispheres as attention shifted back and forth. The third study was designed to test the controversial hypothesis that dyslexia involves a deficit in a specific visual pathway, the magnocellular (M) pathway, from the eye to the brain. Professor Heeger found a strong three-way correlation between individual differences in: (i) M pathway brain activity in areas V1 and MT+, (ii) reading performance, and (iii) performance in a motion discrimination task that depends on M pathway integrity. Subjects with greater fMRI activity were faster readers and better performers in the motion discrimination task.

HOME | BULLETINS | CONTACT US | PREVIOUS ARTICLE | NEXT ARTICLE | THIS ISSUE