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CAREER: Modelling Emergent Behaviour of Gene Networks Controlling Plant Stem Cells

$743,619FY2015BIONSF

North Carolina State University, Raleigh NC

Investigators

Abstract

Climate uncertainty, a growing scarcity of arable land, and the potential to develop renewable sources of bioenergy all focus our attention on the degree to which we depend on plants. One key to improving plant productivity is to understand better the control of their growth and development. Plants possess stem cells, whose division and differentiation is central to plant growth and the building of new organs. Current understanding of plant stem cell regulation does not address well the complex networks of regulation that are involved. This project will use the model plant Arabidopsis to experimentally identify the essential features that govern stem cell regulatory networks in the developing root, and will develop accurate mathematical models that describe the behaviour of these networks. The root captures nutrients essential to the plant, and knowledge of the rules controlling root stem cell behaviour will facilitate the future development of plants for crop improvement. The project will provide cross-training and education to students through the development of courses at the interface between plant biology and bioengineering. These courses will be tailored to the needs of a diverse target audience. The research team will engage a wider audience, ranging from K-12 students to adults, to inform the public on important issues including plant stem cells, plant bioengineering, and crop improvement. A key to systems-level understanding of the molecular mechanisms regulating stem cells is the ability to analyse the dynamics of networks in the context of a living organism. Identifying the essential features that govern stem cell regulatory networks and their emergent behaviours will contribute to an accurate understanding of the design rules governing cell pluripotency. This project integrates techniques derived from biological, mathematical, and engineering science to elucidate mechanisms that regulate plant stem cell fate and maintenance. The project's foundation will be based on the transcriptional profile of two Arabidopsis root stem cell populations, the cortex/endodermal initials (CEI) and xylem (XYL), as well as the quiescent centre cells that maintain the stem cells in their undifferentiated status. Bayesian modelling of transcriptional dynamics, and perturbation testing of the models, have revealed TARGET OF MONOPTEROS3 (TMO3) to be a key regulator of both CEI and XYL stem cells. Novel imaging techniques have been developed that will enable quantitative measurements of diffusion, concentration, and interactions of molecular factors responsible for signalling between stem cells. By integrating these data with mathematical modelling, the project will achieve an improved understanding of how stem cell division is precisely regulated in space and time. The project's research goals are to: 1) characterize the transcriptional signature responsible for stem cell regulation and to test the hypothesis that interacting transcriptional networks operate across different stem cells; and 2) generate mathematical models that incorporate spatial and temporal information to describe communication between stem cells. After determining which parameters are critical to generate a robust mathematical model, models will be generated that describe how regulator signals are propagated between and among cells, and will identify perturbations capable of resetting decision-making signals. These efforts will provide a framework for comparing stem cell development in plants and animals, and will contribute to future plant breeding efforts in the face of climate uncertainty.

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