Understanding and engineering plant gene regulation

Faced with accelerating climate change and rapid population growth, we need crops with higher yields and greater resilience to ensure food security. Crop genome engineering will likely play an important role in meeting future food needs. Gene regulatory sequences are promising targets for crop improvements for two reasons: First, changes in regulatory regions often result in tissue- or condition-specific changes in gene expression, and hence can be less deleterious than coding changes. Second, both evolution and domestication have frequently acted on regulatory DNA. However, to enable targeted engineering of plant gene regulation, we need to better understand plant cis-regulatory elements and their interactions—the regulatory grammar of plants.

Our research focuses on a comprehensive understanding of gene regulatory logic in plants. Using high-throughput assays, we are characterizing the condition- and species-specific activity of tens to hundreds of thousands plant cis-regulatory elements. Leveraging the data produced by these assays and deep learning, we are developing computational models that can predict the activity of novel sequences and enable the design of synthetic cis-regulatory elements with desirable features. Furthermore, we study how different types of cis-regulatory elements interact with one another and with the cellular repertoire of transcription factors and other trans-acting proteins. These studies will lead to a deeper understanding of the rules that govern the activity and strength of plant regulatory DNA and will enable us to accurately predict and manipulate plant gene expression.

In parallel to studying plant regulatory grammar, we are developing a toolkit for transgene-free genome editing of cis-regulatory elements. Current technical solutions for plant genome engineering face public skepticism about transgenic organisms and concerns around off-target effects. We are working on an alternative approach to plant genome engineering by using editing proteins that are expressed in Agrobacteria and subsequently transferred to plant cells without a concomitant transfer of DNA. This system will yield transgene-free plants and reduce the number of off-target mutations since the editing proteins will not be produced constitutively.