Unravelling gene networks to bridge the genotype-to-phenotype gap

Ronan O’Malley, PhD

DOE Joint Genome Institute

Lawrence Berkeley National Laboratory

https://jgi.doe.gov/our-science/scientists-jgi/ronan-omalley/

Unravelling gene networks to bridge the genotype-to-phenotype gap

Phenotypic variations that are central to crop improvement result from either the emergence of novel gene functions and pathways, or through the modifications of gene expression dynamics within the conserved pathways. While both mechanisms can contribute to phenotypic innovations, recent studies suggest that the changes in gene regulation may be more common, particularly in shorter evolutionary time frames and domestication. While comparative transcriptomics along with gene network modeling have proven to be powerful approaches to characterize regulatory plasticity, most studies to date have relied on bulk tissue RNA-seq analysis and as such fail to capture the cell-type resolution required to clearly understand the composition and function of plant gene networks. Furthermore, as changes in gene regulation are a direct consequence of changes in transcription factor binding at promoters and enhancers, comprehensive genome-wide transcription factor binding site atlases are crucial for deciphering how pathways are rewired during domestication and adaptive selection. To address these questions, we are developing integrative approaches to leverage complementary technologies including single-cell transcriptomics and chromatin accessibility assays (single cell RNA-seq and ATAC-seq) along with ultra-high throughput transcription factor binding assay (DAP-seq and multiDAP), to understand how pathways and ultimately plant traits are shaped through alterations in gene expression. I will present our current progress in applying these technologies in important bioenergy plants, fungi and bacteria to develop integrative atlases of gene networks to understand how they control and shape important growth and stress response pathways at the levels of DNA sequence, cell-type and tissue regulation.