SBIR-STTR Award

Using Combinatorial Control To Improve Transgene Expression Specificity In Plants
Award last edited on: 9/20/13

Sponsored Program
STTR
Awarding Agency
NIH : NIGMS
Total Award Amount
$367,711
Award Phase
1
Solicitation Topic Code
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Principal Investigator
Tedd D Elich

Company Information

Grassroots Biotechnology Inc (AKA: Plx Pharma Inc~grassroots Pharmaceuticals Llc)

302 East Pettigrew Street Suite A200
Morrisville, NC 27701
   (919) 747-7400
   N/A
   www.grassrootsbio.com

Research Institution

Duke University

Phase I

Contract Number: 1R41GM100547-01A1
Start Date: 9/5/12    Completed: 9/4/13
Phase I year
2012
Phase I Amount
$367,711
It is currently estimated that 15% of the world's population is undernourished and 5 million childhood deaths a year are attributable to malnutrition. The ability to feed the world in the future will be even more difficult due to population growth, climate change, water scarcity, and competition for land. It is widely recognized that advances in agricultural biotechnology will be required to meet the world's future nutritional needs. In nature, gene expression is regulated at multiple levels including transcription, alternative splicing, transcript stability, and translation. In contrast, the agricutural biotechnology industry has relied primarily on constitutive transcriptional control to regulate the expression of traits introduced into crops. This has been sufficient for the relatively simple trais that have been commercialized to date, but the complex traits that will be needed to meet future food demands are expected to require increased expression specificity. The long term goal of this project is to assemble a portfolio of modular expression elements that can be deployed in a combinatorial fashion to provide predictable and tunable expression solutions to the agricultural biotechnology industry. The goal of the Phase I component of this project is to demonstrate proof-of-concept that heterologous miRNA binding elements and pre-mRNA splicing elements can be used to increase the expression specificity of transcriptional promoters in the model plant Arabidopsis. As a specific product concept, Phase I research will focus on designing a root stele-specific expression cassette useful for regulating traits that target soybean cyst nematode. Our specific aims are to: 1) validate a modular post-transcriptional regulatory element that enhances stele expression specificity, and 2) create stele-specific expression cassettes that are combinatorially controlled by transcriptional promoters and post-transcriptional regulatory elements. Selection of miRNA binding elements will be based on recently published data demonstrating cell type-specific expression patterns of specific miRNAs that are inversely correlated with the expression patterns of their respective targets. Alternative splicing events wil be identified through bioinformatic analysis of cell type-specific RNA-seq and microarray expression data. Identified posttranscriptional regulatory elements will be validated in the context of a constitutive promoter and then tested for their ability to increase the expression specificity of a stele-enriched promoter. After demonstrating proof-of-concept of combinatorial control, Phase II research will expand this approach to crops including economically important cereals like corn.

Public Health Relevance:
It is currently estimated that 15% of the world's population is undernourished and 5 million childhood deaths a year are attributable to malnutrition. The ability to feed the world in the future will be even more difficult due to population growth, climate change, water scarcity, and competition for land. It is widely acknowledged by experts that increased agronomic productivity through biotechnology will be needed to meet future food demands. The goal of this project is to facilitate biotechnology approaches that lead to the production of more crops on less land with fewer resources.

Public Health Relevance Statement:
It is currently estimated that 15% of the world's population is undernourished and 5 million childhood deaths a year are attributable to malnutrition. The ability to feed the world in the future will be even more difficult due to population growth, climate change, water scarcity, and competition for land. It is widely acknowledged by experts that increased agronomic productivity through biotechnology will be needed to meet future food demands. The goal of this project is to facilitate biotechnology approaches that lead to the production of more crops on less land with fewer resources.

NIH Spending Category:
Biotechnology; Climate-Related Exposures and Conditions; Genetics; Nutrition

Project Terms:
Agriculture; Alternative Splicing; Animals; Arabidopsis; Automobile Driving; base; Beryllium; Binding (Molecular Function); Bioinformatics; Biotechnology; Breeding; cell type; Cereals; Cessation of life; Childhood; climate change; combinatorial; Complex; Cyst; Data; design; Development; Elements; Engineering; Event; Farming environment; feeding; Food; Foundations; fungus; Future; Gene Expression; Gene Expression Regulation; Genetic Engineering; Genetic Transcription; Goals; Herbicides; Imagery; improved; in vivo; Industry; Laboratories; Lead; Learning; Malnutrition; meetings; MicroRNAs; mRNA Precursor; Nature; Nematoda; next generation; Nutritional; Pattern; Phase; Physiological Processes; Plant Model; Plant Physiology; Plant Roots; Plants; Population; Population Growth; Post-Transcriptional Regulation; pressure; Production; Productivity; Promotor (Genetics); Publishing; Regulator Genes; Regulatory Element; Research; Resistance; Resources; RNA; RNA Splicing; Site; Solutions; Soybeans; Specificity; Testing; Time; Tissues; trait; Transcript; Transcriptional Regulation; transgene expression; Transgenes; Transgenic Organisms; Translations; Water

Phase II

Contract Number: ----------
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
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Phase II Amount
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