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Abstract
Grant Number: 5R01GM032877-24 Project Title: Regulation of Amino Acid Biosynthesis Genes in Plants
PI Information: Name Title CORUZZI, GLORIA M. gloria.coruzzi@nyu.edu PROFESSOR Abstract: DESCRIPTION (provided by applicant): Our long-term goal is to define the regulatory mechanisms controlling N-assimilation into amino acids in plants. Our work to date has identified key isoenzymes involved in this pathway, shown that their transcriptional regulation reflects levels of cognate amino acids, and uncovered evidence that light, carbon and nitrogen signaling modulate gene expression. We now propose to determine how these various signaling systems interact to coordinate regulation of genes in this pathway and globally affect amino acid synthesis. To accomplish this, which cannot be achieved using standard single-gene/genetic analysis, we have developed an innovative approach that combines math tools for strategic experimental design, with model building, genomics/bioinformatics and molecular genetics. Importantly, this approach exploits "activist" data mining, in which math tools are used not simply for data analysis, but to iteratively construct "experimental spaces" that efficiently test how regulatory signals interact, to enable model building and testing. This mathematically compresses an enormous number of permutations (effects of C, N, light, etc.) into a small and manageable number of testable combinations. We will first use such tools, Combinatorial Design & C:N Matrix, to strategically sample a large series of input variables (Aim 1), and stepwise develop models of regulatory circuits for signal interactions regulation of genes (including dose and kinetic responses) using Boolean logic and visualization methods (Aim 2). Aim 3 will expand the analysis of the N-assimilation regulatory circuit using microarray and metabolome analysis of selected and prioritized treatments. Genes in pathways co-regulated by multiple signals will be identified using new bioinformatic tools we have developed (PathExplore + InteractClass), which also enable correlation with levels of cognate amino acids. Co-regulated genes in pathways will be analyzed for potential cis-regulatory elements and associated transcription factors (where known), to generate testable models for regulatory circuits. These regulatory models of N-assimilation will be tested using mutants in putative C:N sensing components we have isolated using forward and reverse genetic approaches (Aim 4). The synthesis of these aims should allow us to model, predict, and test how perturbations of the regulation of this pathway(s) may be used to enhance N-assimilation, a limiting factor in plant growth affecting agriculture, human nutrition, and health. They also provide a valuable proof-of-principle study for the application of these approaches and tools to model other regulatory circuits in biological and medical systems.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
aminoacid biosynthesis, biological signal transduction, genetic regulation, plant genetics, regulatory gene, structural gene
Escherichia coli, cell growth regulation, enzyme activity, gene expression, gene mutation, genetic transcription, isozyme, mathematical model, mutant, nitrogen metabolism, photosynthesis, plant protein
Arabidopsis, electrophysiology, genetically modified plant, polymerase chain reaction, tissue /cell culture
Institution: NEW YORK UNIVERSITY OFFICE OF SPONSORED PROGRAMS NEW YORK, NY 100122331 Fiscal Year: 2007 Department: BIOLOGY Project Start: 01-DEC-1983 Project End: 30-APR-2009 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: CDF