Role of SOG1 and related NAC transcription factors in plant DNA Damage Response
Project description
The DNA Damage Response (DDR) is a large signaling network that senses and responds to different types of DNA damage. It controls DNA repair, cell cycle progression, apoptosis and all other responses to replication stress. The DDR network is highly conserved between animals and plants, especially at the level of detection and signal transduction. A major difference, however, is the total absence in plants of a homolog of the well-known tumor suppressor p53. Instead, a set of plant-specific transcription factors called NAC proteins take over these tasks. The name of this family is derived from three transcription Arabidopsis transcription factors: NAM (no apical meristem), ATAF1–2 (Arabidopsis thaliana activating factor), and CUC2 (cup-shaped cotyledon). Most NACs carry out highly specific tasks, but one sticks out as more general and a functional equivalent of p53: SOG1. In contrast to p53, data on SOG1 and related NACs remains scares and little is known about the mechanisms used by these proteins to control the differential regulation of hundreds of genes.
The Loris group studies the structure-function relationships of NAC transcription factors with an emphasis on SOG1. We wish to understand how SOG1 and other NACs control cell cycle arrest upon DNA damage. To this end, we want to find out what the interaction partners are of SOG1 including other NAC proteins that may modify its DNA specificity via the formation of heterodimers. We want to understand the functional role of the large intrinsically disordered domain as a possible transcription activation domain and as a hub for other protein partners and how the phosphorylation of this domain by ATM, ATR and possibly other kinases affects these functionalities. We further aim to understand the DNA specificity of these proteins and how these are modified via interactors and post-translational modification, and whether there is a role of liquid-liquid phase separation in the functioning of NACs. Specific projects can be discussed that involve structural biology (X-ray crystallography, NMR and SAXS) combined with protein chemistry (including ITC, CD and mass spectrometry) and protein engineering. You will bring in your own expertise for these or complementary (e.g. in planta expertise) techniques but will also be able to acquire fresh skills.
As a MSCA Fellow you would be hosted within the VIB-VUB Center for Structural Biology at the Vrije Universiteit Brussel. This multi-disciplinary center encompasses more than 100 researchers divided over 12 research groups and contains state-of-the-art in-house facilities for protein production, cryo-EM, X-ray crystallography, NMR, SAXS, molecular biophysics and molecular biology. The work will be carried out in collaboration with the VIB and UGent department of Plant Systems Biology where, depending on your interests, you will also have the opportunity to participate in in planta work.
About the research Group
Structural Biology Brussels
Structural Biology Brussels (SBB) is headed by Prof. Dr. ir. Jan Steyaert and focusses on research in structural biology. We study the structure of proteins and DNA from the molecular to the atomic level. By determining the position of atoms in a macromolecule (proteins, for example, contain thousands of atoms) we can derive how such molecules can act as tiny machines, and determine how they interact with each other. The end goal of this research is to unravel the complex machinery that makes cells work.
Our work on fundamental aspects of biology and biochemistry also leads to important industrial and biomedical applications. If you know how a protein works, you can also find out why these tiny machines sometimes fail to work as they should. For example, if we learn more about the molecular cause of certain hereditary diseases, or the reason why bacteria can resist antibiotics, then this serves as the first step in rational drug design: developing novel drugs based on knowledge of protein structure and their mode of action.
SBB is a large research groep with about ten principal investigators. This critical mass allows us to employ many complementary state-of-the-art techniques in the field, whose results we combine to obtain a picture of the macromolecules under study that is as accurate and correct as possible. The most important technique we use is X-ray diffraction on protein crystals, as well as NMR spectroscopy, SAXS and electron microscopy. These are supported by our expertise in biochemistry, protein engineering, molecular biophysics and computational structural biology.
At the SBB we also perform fundamental research into the crystallisation and nucleation of biological macromolecules; this goes as far as employing microgravity in the International Space Station.
Finally, the SBB is part of the Structural Biology Research Center (SBRC). The SBRC is part of the Vlaams Instituut voor Biotechnologie (VIB), an institute which encompasses leading research groups with biotechnology interests over the Flemish universities. The aim of the VIB is to translate results from fundamental research in medicine, agriculture and industry.