Multiscale Models of Bacterial Chemotaxis and Phase Segregation in Axons

Ohio State University, The, Columbus OH

Investigators

Abstract

This project investigates fundamental questions of a multiscale nature in two biological systems. The first topic concerns chemotaxis of cell populations, which is the directed movement of cells in response to external chemical signals. Current continuum models for chemotaxis of cell populations using partial differential equations are phenomenological and do not match recent experimental data. This research investigates this issue in the context of bacterial chemotaxis, and derive continuum models from cell-based models based on the detailed biochemistry of cell signaling. This task involves development of new multiscale methods that deal with nonlinearities of single-cell dynamics and overlapping time scales. The second topic concerns the dynamics and organization of the axonal cytoskeleton. A fundamental question in axonal physiology is to understand how the structure of the axonal cytoskeleton is developed and maintained in health and how it gets perturbed in diseases. This research investigates the mechanisms that lead to the segregation of axonal cytoskeletal molecules observed in diseases using multiscale models, and will be conducted in close collaboration with experimentalists. Complex biological systems involve multiple space and time scales. To completely understand these systems, multiscale models and methods are essential tools. This research addresses questions of a multiscale nature in two biological systems by developing new multiscale models and methods. The first concerns the directed cell movement in response to chemical signals, which is crucial in bacteria-induced infections, bioremediation, wound healing, cancer metastasis, and embryonic development. This research will lead to quantitative, mechanistic models for directed movement of bacterial populations. These models will enhance our ability to predict and control health problems such as bacteria-associated infections and environmental problems such as bioremediation. The resulting multiscale analysis framework is broadly applicable to study collective movement of other types of cells, ants, birds and animals, and thus this research has far-reaching impacts in medicine and ecology. The second topic concerns the physiology of axons, which are long thin projections of nerve cells. Maintaining the regular shape and organization of the axonal cytoskeleton is critical for the normal functioning of neurons. How is the normal organization of the axonal cytoskeleton maintained and established in health? How is it perturbed in neurodegenerative diseases? This research investigates these questions using multiscale models that integrate the detailed biology of the axonal cytoskeletal molecules. This research will shed light on the underlying mechanisms of many neurodegenerative diseases such as amyotrophic lateral sclerosis. This project will also involve cross-disciplinary training of undergraduate and graduate students with diverse backgrounds at the interface between multiscale modeling and wet-lab experiments.