INTEREST AREA: Enabling Technologies
The ability to effectively and efficiently improve crops through genetic engineering relies on finely tuned expression of integrated genes that is predictable in varying genetic backgrounds1. However, the structural organization of the eukaryotic genome is complex. The expression of a gene is not only influenced by its associated regulatory elements but may also be affected by regulatory elements of nearby genes or by transcriptional interference between genes (Figures 1 and 2). One strategy for improving the predictability of gene expression is to use insulator elements to shield gene expression from outside influence (Figures 1d and 2c).
Chromatin insulators were first discovered in animals based on their ability to block enhancer-promoter interactions (enhancer blocking insulators) and/or serve as barriers against the spread of silencing effects of heterochromatin (barrier insulators)2. To date, little is known about insulators in plant systems. Consequently, we are seeking collaborations to identify plant-derived or novel-synthetic DNA sequences that protect gene expression from outside influence and improve predictability in plants.
At Corteva Agriscience, our goal is to develop effective, sustainable, and durable solutions to agricultural challenges. Improving the predictability of gene expression is core to delivering robust genetically engineered traits. We invite public and private sector scientists to join in our efforts by submitting a research proposal to discover plant-derived or synthetic insulator-like elements.
Figure 1. Transcriptional interference reduces the predictability of gene expression in plants. (a) represents expression of Gene 1 without influence from neighboring genes; (b) represents expression of Gene 2 without influence from neighboring genes; (c) represents transcriptional interference between two proximal genes, Gene 1 and Gene 2, in a genomic context; (d) represents a hypothetical scenario where an insulator element* (< 500 bp) shields both genes from transcriptional interference.
Figure 2. A transcriptional enhancer reduces the predictability of gene expression in plants by influencing expression of neighboring genes. (a) represents the expression of genes in the absence of an enhancer element; (b) represents an enhancer’s effects on the expression of two nearby genes; and (c) represents a hypothetical scenario where an insulator element* (< 500 bp) shields a nearby gene from activation by an enhancer.
*The location of insulator elements in Figures 1 and 2 represent possible arrangements for simplicity. Other arrangements may be possible.
1 Singer, S.D., Liu, Z., and Cox, K.D, (2012). Minimizing the unpredictability of transgene expression in plants: the role of genetic insulators. Plant Cell Rep. 31:13-25.
2 Heger, P. and Wiehe, T. (2014). New tools in the box: An evolutionary synopsis of chromatin insulators. Trends in Genetics 30:161-171.
This opportunity is now closed.
We are seeking non-confidential proposals that describe a research plan to identify plant-derived or novel-synthetic DNA-based insulator elements.
Approaches not of interest:
Proposals should include:
* Indirect costs available to academic and nonprofit research institutes only
For submissions received by 5:00 pm PDT on April 30, 2021:
The outcome of the research from funded proposals under this RFP is to be deposited in the public domain and accessible by all (no intellectual property filings shall occur).