Towards an integrative mechanistic theory of within-host disease dynamics:
Overview
This $1.6 million
grant from NSF/NIH aims to study how certain nutrients affect
the development of disease in humans and animals. The PIs are Yang Kuang
(director), Jim Elser (SoLS), Tim Newman (Physics), John Nagy (Scottsdale CC),
Marilyn Smith (Medical Center at U. of Kansas) and Val Smith (EEB at U. of
Kansas).
Just recently, observations that vitamin D supplements are effective against
breast cancer and that iron nutrition affects HIV progression have grabbed
newspaper headlines. Researchers are increasingly aware of many subtle
impacts of certain chemicals on some diseases. For example, older
Americans may remember when conventional wisdom told them to take iron
supplements to combat iron deficiency. However, recent research suggests
that too much iron in the diet might actualy supply a key nutrient that is required
for the development of that disease. The study of such subtle impacts is a natural
extension of the newly emerged subject called biological stoichiometry.
Biological stoichiometry has proven to be an important new lens through which
to view and understand 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 and 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. It is compellingly clear to us that the time is ripe for such a
broad-based and interdisciplinary research program.
A major strength of the proposed work is the tightly woven threads of
theoretical and experimental research. Our primary aim is the construction of
predictive and verifiable theoretical models which can uncover the effects of
stoichiometric interactions in within-host disease dynamics. Such theories will
be built in a modular fashion, starting with simple deterministic models, and
then progressively adding stochasticity, spatial heterogeneity, and genetics.
The ultimate goal of this research is to uncover, via the theory of biological
stoichiometry, new ways to understand and ultimately control human disease.
The successful outcome of this project will be robust and experimentally
calibrated mathematical theories of disease-host interactions that can then
be applied to a wide variety of human diseases such as cancer, HIV,
diabetes, and newly emerging infectious diseases.
the development of disease in humans and animals. The PIs are Yang Kuang
(director), Jim Elser (SoLS), Tim Newman (Physics), John Nagy (Scottsdale CC),
Marilyn Smith (Medical Center at U. of Kansas) and Val Smith (EEB at U. of
Kansas).
Just recently, observations that vitamin D supplements are effective against
breast cancer and that iron nutrition affects HIV progression have grabbed
newspaper headlines. Researchers are increasingly aware of many subtle
impacts of certain chemicals on some diseases. For example, older
Americans may remember when conventional wisdom told them to take iron
supplements to combat iron deficiency. However, recent research suggests
that too much iron in the diet might actualy supply a key nutrient that is required
for the development of that disease. The study of such subtle impacts is a natural
extension of the newly emerged subject called biological stoichiometry.
Biological stoichiometry has proven to be an important new lens through which
to view and understand 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 and 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. It is compellingly clear to us that the time is ripe for such a
broad-based and interdisciplinary research program.
A major strength of the proposed work is the tightly woven threads of
theoretical and experimental research. Our primary aim is the construction of
predictive and verifiable theoretical models which can uncover the effects of
stoichiometric interactions in within-host disease dynamics. Such theories will
be built in a modular fashion, starting with simple deterministic models, and
then progressively adding stochasticity, spatial heterogeneity, and genetics.
The ultimate goal of this research is to uncover, via the theory of biological
stoichiometry, new ways to understand and ultimately control human disease.
The successful outcome of this project will be robust and experimentally
calibrated mathematical theories of disease-host interactions that can then
be applied to a wide variety of human diseases such as cancer, HIV,
diabetes, and newly emerging infectious diseases.
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National Science Foundation DMS- infrastructure program |
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National Science
Foundation DMS- infrastructure program