The Computable PlantThe Computable Plant

Claire SchulkeyClaire Schulkey

Kiri HamakerKiri HamakerCalifornia Institute of Technology

Dr. Bruce E. Shapiro

OverviewOverviewWhat are the shoot apical meristem (SAM) What are the shoot apical meristem (SAM)

and auxin?and auxin?What is our project?What is our project?How does our project involve the SAM and How does our project involve the SAM and

auxin?auxin?How are we going to make an auxin How are we going to make an auxin

transport model?transport model?

Shoot Apical Meristem (SAM)Shoot Apical Meristem (SAM)

The SAM is a bunching of The SAM is a bunching of plant stem cells at the plant stem cells at the very tip of a plant stem. very tip of a plant stem. The SAM is at a The SAM is at a dynamic equilibrium, dynamic equilibrium, maintaining a stock of maintaining a stock of stem cells while stem cells while allowing other cells to allowing other cells to differentiate into differentiate into specific plant tissues.specific plant tissues.

A SAM and forming leaf primordia

http://www.science.siu.edu/landplants/Lycophyta/lycophyta.html

Auxin is a signaling Auxin is a signaling hormone in plants hormone in plants believed to influence believed to influence a variety of a plant’s a variety of a plant’s physiological physiological processes though processes though regulation of gene regulation of gene expression.expression. Indole-3-acetic acid (IAA),

the most prevalent auxin in plant growth

Image released to public domain by author, and modified by C. Schulkey

Auxin Auxin

Project OverviewProject Overview

Create a working model of how auxin is transported Create a working model of how auxin is transported throughout a network of cells.throughout a network of cells.

This model represents a 2-D This model represents a 2-D slice of the SAM in the slice of the SAM in the L1 layer layer with chemical reactions denoted with chemical reactions denoted by differential equations with by differential equations with robust initial conditions, robust initial conditions, formulated by the xCellerator formulated by the xCellerator plugin in Mathematica.plugin in Mathematica.

Image released to public domain by author, and modified by Kiri Hamaker

The Computable PlantThe Computable Plant A long term project whose encompassing goal is to A long term project whose encompassing goal is to

determine: determine: How genetic makeup and How genetic makeup and environment affect developmental environment affect developmental processes involved in forming tissue processes involved in forming tissue and organs in undifferentiated cellsand organs in undifferentiated cells..

This project has implications in forefront This project has implications in forefront biomathematics, systems biology, and biomathematics, systems biology, and microbiological imaging and has played microbiological imaging and has played a part in key development of a part in key development of revolutionary tools in the field.revolutionary tools in the field.

Image released to public domain by author

ToolsTools

SBML SBML (Systems Biology (Systems Biology

Markup Language)Markup Language)

xCelleratorxCellerator

MathematicaMathematica

SBMLSBML Low-level computer-Low-level computer-

readable formatreadable format Created for modeling Created for modeling

microbiological pathwaysmicrobiological pathways Users employ high-level Users employ high-level

tools to interface with tools to interface with SBMLSBML

In Mathematica, we use a In Mathematica, we use a specific form of SBML specific form of SBML created by Dr. Shapiro: created by Dr. Shapiro:

MathSBMLMathSBML

Sample code taken from basic model definition handbook:

Systems Biology Markup Language (SBML) Level 1: Structures and Facilities for Basic Model Definitions, Michael Hucka, Andrew Finney, Herbert Sauro, Hamid Bolouri, http://sbml.org/specifications/sbml-level-1/version-2/html/sbml-level-1.html

xCelleratorxCellerator User-friendly Mathematica packageUser-friendly Mathematica package Accepts inputs into chemical reactions Accepts inputs into chemical reactions

selectable through an organized selectable through an organized xCellerator palettexCellerator palette

xCellerator translates chemical xCellerator translates chemical reactions into sets of ordinary reactions into sets of ordinary differential equations Mathematica differential equations Mathematica can usecan use

xCellerator package functions with xCellerator package functions with multiple plugins for employing sets of multiple plugins for employing sets of ODEs to create models as desired, ODEs to create models as desired, including:including: MathSBML – interprets/edits SBMLMathSBML – interprets/edits SBML Cellzilla – creates/manipulates cell Cellzilla – creates/manipulates cell

networksnetworks Qhull – supports coordinate modeling Qhull – supports coordinate modeling

in 2D, 3D, and further dimensionsin 2D, 3D, and further dimensions

MathematicaMathematica

Powerful and flexible Powerful and flexible mathematical computing mathematical computing softwaresoftware

Main framework for Main framework for computing lists of computing lists of differential equations differential equations generated by xCelleratorgenerated by xCellerator

Project Stepping StonesProject Stepping Stones

1.1. Determine the important processes influencing Determine the important processes influencing auxin transport and Aux/IAA regulationauxin transport and Aux/IAA regulation

2.2. Create a model for a single cellCreate a model for a single cell

3.3. Expand the single cell model to a networkExpand the single cell model to a network

Step 1: Process SelectionStep 1: Process Selection

Auxin Influx/Efflux Auxin Influx/Efflux ProteinsProteins PIN1, AUX1 (EIR1?, PIN1, AUX1 (EIR1?,

AXR4?)AXR4?) These auxin transport These auxin transport

proteins, with passive proteins, with passive diffusion, move auxin into diffusion, move auxin into

and out of a celland out of a cell..

Proteins and genes involved Proteins and genes involved in in Aux/IAAAux/IAA protein pathway protein pathway ARFARF,, auxin response factor auxin response factor Active/inactive Aux/IAA geneActive/inactive Aux/IAA gene Proteasomal degredation Proteasomal degredation Charged and uncharged Charged and uncharged

auxinauxin

Step 2: Model a single cellStep 2: Model a single cell

Simple Overview

Step 2: Model a single cellStep 2: Model a single cell

Step 3: A network of cells (future work)Step 3: A network of cells (future work)

The model can then be The model can then be expanded to expanded to encompass a number encompass a number of cells to model the of cells to model the flow of auxin in a flow of auxin in a network. Visual network. Visual representations of the representations of the auxin flow may be auxin flow may be created for more created for more complete understanding complete understanding of the model’s of the model’s implications.implications.

Image taken from wild-type Wuschel activity simulation:Jönsson, Henrik et. al. Modeling the organization of the WUSCHEL expression domain in the shoot apical meristem. Bioinformatics 21(S1):i232-i240 (July 2005).

AcknowledgementsAcknowledgements

Dr. Bruce E. ShapiroDr. Bruce E. Shapiro Biological Network Modeling Center (BNMC)Biological Network Modeling Center (BNMC) The Computable Plant TeamThe Computable Plant Team SoCalBSI mentors and studentsSoCalBSI mentors and students

Special Thanks to:Special Thanks to:NIHNIH

NSFNSF

Los Angeles – Orange County Biotechnology CenterLos Angeles – Orange County Biotechnology Center