Collaborative Research: Towards an Integrative Mechanistic Theory of Within-Host Disease Dynamics

Arizona State University, Scottsdale AZ

Investigators

Abstract

Abstract Awards: DMS 0342388, 0342239, 0342325 Principal Investigators: Yang Kuang, Val Smith, Marilyn S. Smith This multi-campus team is studying processes within a single biological host that can be described by models inspired by ecological stoichiometry, the study of the balance of energy and multiple chemical resources (usually elements) in ecological interactions. These concepts have been broadened by their extension to biological stoichiometry, which has proven to be an important new lens through which we can view and understand complex biological interactions. Within this general theory, the cycling and utilization of energy and multiple nutrients by organisms and their constituent cells occupies a central position. With its emphasis on the flow of elemental matter, such as carbon, nitrogen, and phosphorus, stoichiometric theory covers multiple biological scales. It also allows, via rigid physical and chemical constraints, the construction of robust mechanistic and predictive models. Originally formulated and verified in the fields of limnology and plant ecology, biological stoichiometry has recently been applied at physiological scales to such diverse areas as organism development and tumor growth. In this proposal we aim to synthesize and apply theoretical and empirical approaches to biological stoichiometry within the grand framework of internal disease. Recent headline-grabbing findings that connect nutritional factors to disease dynamics indicate there is an increasing need for stoichiometry-based mathematical models of internal disease that track the effects of potentially limiting resources. The proposed work weaves together threads of theoretical and experimental research. Our primary aim is the construction of predictive and verifiable theoretical models which can begin to explicitly deal with the effects of stoichiometric interactions in within-host disease dynamics. Such models will be built in a modular fashion, starting with simple deterministic models, and then progressively adding stochasticity, spatial heterogeneity, and genetics. At each step the models will be challenged, calibrated, and tested by in vitro laboratory experiments. The proposed work will have a broad impact in both science research and education, and eventually in internal disease management and treatment. Regarding the former, our research team is truly interdisciplinary, with group members in mathematics, theoretical physics, ecology, and biomedicine. Our collaborative efforts will provide undergraduate and graduate students and junior scientists of diverse ethnic/racial backgrounds with first-hand educational experience in cross-disciplinary communication and exploration. The current proposal is a step towards new ways to understand disease, aiming to develop robust and experimentally calibrated mathematical theories of disease-host interactions that can be applied to a wide variety of diseases. We firmly believe that such theories have a central role to play in present and future research. These grants for proposals submitted as a collaborative proposal from three institutions are made under the Joint DMS/NIGMS Initiative to Support Research Grants in the Area of Mathematical Biology. This is a joint competition sponsored by the Division of Mathematical Sciences and the Directorate for Biological Sciences at the National Science Foundation and the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health.