Opportunity Details

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Plant-derived insulator elements for predictable gene expression

Focus 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
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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 1

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. 

*The location of insulator elements in Figures 1 and 2 represent possible arrangements for simplicity. Other arrangements may be possible.

Figure 2
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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.

Figure 2

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.

*The location of insulator elements in Figures 1 and 2 represent possible arrangements for simplicity.  Other arrangements may be possible.

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References

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.

What We Are Seeking

We are seeking non-confidential proposals that describe a research plan to identify plant-derived or novel-synthetic DNA-based insulator elements.

Must haves:

  • A stepwise method to identify enhancer blocking insulators or other DNA elements that protect gene expression from the influence of nearby regulatory elements or transcriptional interference.
  • Indication of functionality in plants. Evidence may be literature-based, in-planta, in vitro, or in silico.

Nice-to-haves:

  • Sequences ideally 500 base pairs or less in length
  • Plant-based assay(s) for screening enhancer-blocking or transcriptional interference activities of candidate insulators

Approaches not of interest:

  • Sequences/systems derived from non-plant organisms, including model animal systems, are not desired
  • Proposals that focus on transcriptional terminators as insulators are not desired
  • Proposals that focus on blocking the spread of heterochromatin (barrier insulators) are not desired.

Proposals should include:

  • A high-level timeline to proof of concept, ideally within a 12-month period
  • Expertise, equipment and facilities you have and/or need to execute the proposal
  • A breakdown of the estimated project cost (up to $50,000 including a maximum of 10% indirect costs*)

Download the Collaboration Proposal Template

Awarded Submissions

  • Funding (up to $50,000 including a maximum of 10% indirect costs*)
  • Opportunities for extended collaboration

* Indirect costs available to academic and nonprofit research institutes only

Who Should Apply

  • Scientists with expertise in regulation of gene expression and/or chromatin structure in plants
  • Scientists with expertise in regulation of gene expression and/or chromatin structure in other eukaryotic biological systems that can be applied to plants
  • Any creative and innovative scientist with ideas that can be adapted to solve this challenge
  • Institutions, organizations, entrepreneurs, or individuals with related experience and interest

Program Details

For submissions received by 5:00 pm PDT on April 30, 2021:

  • We will evaluate your submission and notify you of its status by June 30, 2021.
  • An Open Innovation representative will contact selected applicants to provide additional details on the selection process.

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).  Publication rights to remain with the selected applicant.

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