PhD Defence: Peter Sørensen Millard
PhD Candidate
Peter Sørensen Millard
Title of PhD Thesis
Structural and functional evolution of R2R3 transcription factors
Abstract
Transcription factors (TFs) are involved in the regulation of all biological processes in plants. Coordinated control of gene expression is achieved through integration of internal and external cues, which is accomplished on a molecular level through dynamic complex formation and modification of TFs. Many binary interactions have been mapped between plant TFs. Yet the exact binding sites mediating interaction are often unknown, although details of the binding mechanism define the interaction parameters that govern activity in vivo. Additionally, within the last few decades, intrinsically disordered regions in proteins have been shown to confer specific molecular functions while lacking stable structures, and these regions are especially prevalent in signalling and regulatory proteins, including TFs. This discovery has had a significant impact on the animal TF field, where increased focus on understanding molecular functions and mechanisms in a structural context has enhanced the understanding of biological processes and regulation. However, very few plant TFs have been structurally characterised. In this thesis, protein structure and molecular functions of TFs from the MYB family are investigated from different angles. The MYB family is structurally uncharacterised, yet one of the largest TF families known and its members regulate a vast array of biological processes. Members of the MYB family regulating the well-studied pathway of glucosinolate biosynthesis serve as models to investigate structure and protein level regulation of MYB TF activity.
A comprehensive analysis of predicted structure suggested that intrinsically disordered regions are common within the protein family, and experimental structural characterisation validated some of these predictions for two MYB TFs. New interacting protein-level regulators were identified and mechanistically linked to altered glucosinolate profiles. The binding site mediating interaction between MYB and MYC TFs regulating glucosinolate biosynthesis was mapped and characterised, allowing accurate prediction of new interactors, and suggesting a correlation between binding affinity and TF activity. Attempts at exploring the evolution of these MYB-MYC interactions revealed the same binding site in many organisms throughout the angiosperm lineage, and a validated binding site instance in an organism that does not produce glucosinolates, suggesting that MYB-MYC interactions mediated by this binding site are involved in regulating more ancient processes in plants.
Supervisors
Associate Professor Meike Burow, University of Copenhagen
Professor Birthe B. Kragelund, University of Copenhagen
Assessment Committee
Dr. Tamara Gigolashvili, University of Cologne, Germany
Dr. Ralf Stracke, Bielefeld University, Germany
Associate Professor Mathias Pribil, University of Copenhagen (Chair)
Reception
The defence will be followed by a reception in room R322 & R323, Thorvaldsensvej 40, 3rd floor, 1871 Frederiksberg