(343h) K-Ath - Towards a Multi-Tissue Kinetic Model of Arabidopsis thaliana

k-ath - Towards a Multi-tissue
Kinetic Model of Arabidopsis thaliana

Wheaton Schroeder and Rajib Saha

The University of Nebraska – Lincoln, Lincoln, NE

Arabidopsis thaliana has been a model system for
modern plant science for the past three decades due to its small genome, short
lifecycle, and ease of genetic manipulation. Its prominent role in omics and
plant science research makes it an ideal choice for the creation and integration
of emerging omics-based tools, including metabolic modeling of metabolism. Such
computational modeling of metabolism is now an indispensable tool to drive the
processes of understanding, discovering, and redesigning of any biological
systems. Although Flux Balance Analysis (FBA) is the primary tool used for this
purpose, it has significant limitations due to the lack of reaction kinetics,
chemical species concentration, and metabolic regulation. These are critical to
the understanding and subsequent design of engineering interventions directed
to overproduction of specific bioproducts or
improvement of plant performance, particularly in the presence of feedback
regulation. Several metabolic models for A.
thaliana already exist, and most regulatory interactions are well studied
and documented. In addition, omics data is widely available for A. taliana as
a model plant system including genomics, fluxomics, transcriptomics, and metabolomics. Hence, combining and
advancing this knowledge in a kinetic model framework will allow us to study
the interactions among biosynthesis pathways and individual tissue-types, thus
proposing the in silico
design of useful engineering interventions for A. thaliana. Moreover, this research will showcase
the value of a plant-scale kinetic model for answering these questions in other
plant species.

In this
work, we are developing a plant-scale core metabolic network including such
pathways as starch and sucrose metabolism; glycolysis and gluconeogenesis;
citrate cycle; all amino acid biosynthesis pathways; pyruvate metabolism; the
pentose phosphate pathway; photosynthesis and photorespiration pathways; and
various transport and uptake pathways. At present, we have completed the draft
development of three tissue-specific metabolic models: leaf (282 genes, 109
metabolites, and 191 reactions), seed (274 genes, 153 metabolites, and 222
reactions), and stem (12 genes, 54 metabolites, and 91 reactions). Moving
forward, we will develop a root metabolic model, combine these four models in a
plant-scale metabolic model, and using fluxomic,
metabolomics, and transcriptomic data we will develop
kinetic equation form for each reaction. Note that these metabolic models are
restricted to core primary metabolism mainly due to the high computational
requirements of the kinetic model framework. By decomposing each reaction to
mass action kinetics, the rate constants for each mass action step will be determined with respect to fluxomic
data, allowing us to solve for the kinetic constants of each kinetic equation
in the system. Future work for this project includes sub-dividing existing
tissue models, such as stem into xylem and phloem, and adding additional tissue
types. Finally, this kinetic modeling framework of a model plant is
transferable to other plant systems (provided the omics datasets are available
for that species) to provide in silico design of useful engineering interventions.