Award Abstract #0342388
Collaborative Research: Towards an Integrative Mechanistic Theory of Within-Host Disease Dynamics

NSF Org:	DMS
Initial Amendment Date:	June 15, 2004
Latest Amendment Date:	May 17, 2007
Award Number:	0342388
Award Instrument:	Continuing grant
Program Manager:	Christopher W. Stark DMS Division of Mathematical Sciences MPS Directorate for Mathematical & Physical Sciences
Start Date:	July 1, 2004
Expires:	June 30, 2008 (Estimated)
Awarded Amount to Date:	$1223345
Investigator(s):	Yang Kuang kuang@asu.edu(Principal Investigator) James Elser (Co-Principal Investigator) Timothy Newman (Co-Principal Investigator) John Nagy (Co-Principal Investigator)
Sponsor:	Arizona State University ORSPA TEMPE, AZ 85287 480/965-5479
NSF Program(s):	MATHEMATICAL BIOLOGY, MATHEMATICAL SCIENCES
Field Application(s):	0000099 Other Applications NEC
Program Reference Code(s):	OTHR,7303,7242,4075,0000
Program Element Code(s):	7334,7229

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.

Please report errors in award information by writing to: awardsearch@nsf.gov.