G Bard Ermentrout - US grants

This award provides support for a three year continuing award, a renewal of the BBSI@PITT:Simulation and Computer Visualization of Biological Systems at Multiple Scales, at the University of Pittsburgh, under the direction of Dr. Ivet Bahar. This program offered since 2002 by the University of Pittsburgh (lead institution), the Pittsburgh Supercomputing Center, Duquesne University, and Carnegie Mellon University, will host a ten week summer program for a total of 39 undergraduate and graduate students, 13 per year, for a total of three years. The students will have strong analytical and quantitative skills and high potential for careers in Computational Biology, Bioengineering, or Bioinformatics. BBSI@Pitt will continue to focus on computational and mathematical approaches to understanding the function and dynamics of molecular and cellular systems using known structure, biochemical pathways and other data, much of which is increasingly accumulated in web accessible dateabases.

The objectives of BBSI@Pitt are to provide students with a unique training and research experience through a series of cross-disciplinary lectures, computational laboratory sessions, and independent research opportunities not available in traditional undergraduate programs; broaden the student's view of post-genomic computational and mathematical research areas in molecular, cellular, and systems biology; and motivate students to pursue careers in the field.

Computational Biology, Bioengineering, and Bioinformatics exist at the interface of many different fields, and individuals with truly cross-disciplinary expertise are quite rare. BBSI@Pitt will continue to have a broad impact on the field by identifying and encouraging promising young students through intensive cross-disciplinary mentoring, providing advice and guidance for career options, and thus contributing to transforming the new generation's approach to biomedical computing problems of far greater complexity than those accessible to earlier generations.

This project is being co-funded by the Directorate for Mathematical and Physical Sciences (MPS)/ Office of Multidisciplinary Activities (OMA) and the Division of Mathematical Science (DMS), the Directorate for Computer and Information Science and Engineering (CISE)/ Division of Information and Intelligent Systems (IIS) , the Directorate for Engineering/ Division of Engineering Education and Centers (EEC), and the National Institutes of Health (NIH)/National Institute of Biomedical Imaging and Bioengineering (NIBIB).

How we perceive the world is governed both by the sensory inputs with which we are constantly bombarded, by ongoing activity in the brain, and by our previous experience. This activity as well as the natural wiring of the nervous system shapes the spontaneous behavior of our brains and this spontaneous activity strongly modulates the sensory inputs. In this project, computational and mathematical models of neurons (the cells that make up the brain) are used to understand what kinds of spontaneous behavior are possible, how this depends on the wiring and how this activity interacts with sensory inputs. The ongoing and evoked behavior is carefully controlled by a balance of positive (excitatory) and negative (inhibitory) influences. The loss of this balance can disrupt normal behavior and lead to diseases such as epilepsy and schizophrenia. Mathematical models of the nervous system provide a way to test hypotheses put forth by experimenalists and to also suggest new experiments based on the predictions of these models.

Ongoing activity in the nervous system and how it impacts sensory and other inputs is the subject of much recent experimental activity. In particular, it is clear that the intrinsic interactions between neuronal circuits in absence of inputs can have a strong impact on how the system responds to incoming stimuli even at the large scale cognitive level. Thus, nonlinear dynamics methods will be applied to problems in theoretical neuroscience dealing with this question. Various forms of spatiotemporal activity are observed in experiments which include spatially localized activity, oscillations, and propagating waves. Perturbation and numerical methods will be used to analyze the dynamics of these patterns when subjected to various stimuli such as flickering light, localized or moving stimuli, and spatially periodic patterns. Uniform flickering stimuli lead to the perception of moving geometric patterns and these can be explained by the analysis of mean field models of visual cortex. In collaboration with an experimental group we will use the modeling to make predictions about how this percept is altered as parameters of the flicker vary. Related to this is the appearance of flicker when presented with high contrast spatially periodic patterns. Stability of the steady periodic state will be studied in order to see if the appearance of oscillations is the result of a Hopf bifurcation. This effect may also offer an explanation for why some images (such as op art) can induce visual discomfort. The existence an properties of traveling waves in nonlocally connected networks will also be studied in this project.