Keita Tanaka: Reverse-engineering DNA-binding specificity of auxin response transcription factors​

The development and environmental response of multicellular organisms as well as division and migration of unicellular organisms are regulated by concerted expression of a few hundred to several thousand genes. Taking firm control of gene expression is therefore a critical requirement for engineering organisms, for example towards crop improvement. We are aiming to unlock the structural basis that defines interaction between key components in the transcriptional network that mediates responses to auxin, a central signaling molecule. This fundamental knowledge will be used to repurpose the auxin system and consequently achieve a spatiotemporally tunable gene regulatory system in plants.

Towards this goal, I am trying to develop two biological engineering approaches based on currently solved atomic structures of ARF proteins, central transcription factors for cellular auxin response. One objective in my project is to decode the nucleotide-amino acid correspondence that defines the affinity between ARFs and its target DNA motifs, which will enable engineering the binding specificity of ARFs to confer auxin responsiveness to any gene.

A second objective is to rewire auxin response by rearrangement of ARF-targeted DNA motifs. Inspired by the structural analysis having indicated that importance of configuration of motifs in ARF-DNA interaction, I will transform the ARF-mediated transcriptional network using genome engineering techniques. Consequently, we will obtain a new insight regarding target-discrimination mechanisms of transcription factor and novel strategy to modulate cellular signal responses.

The research outcomes will be a milestone expanding the knowledge base of gene regulation mechanisms and plant development as well as technology base to engineer biological processes, potentially leading to improving crop yield.