Research
What do we study, and why?
In order to enhance their chances of survival and reproductive success, plants need to fine tune their growth and development in response to a wide range of diverse internal signals (e.g. hormones) and environmental cues (e.g. temperature or oxygen availability).
We are interested in understanding the cellular mechanisms that plants have evolved to perceive these signals and transduce them into appropriate developmental and physiological outputs, with a particular focus on targeted protein degradation. We use a diverse range of molecular, genetic, biochemical and physiological approaches to achieve this, primarily in the model plant Arabidopsis.
Targeted protein degradation
Regulation of protein turnover is essential for controlling cellular responses and developmental outputs. In eukaryotes, the ubiquitin proteasome system (UPS) is the predominant pathway for targeted protein degradation; in this system, conjugation of ubiquitin molecules to protein substrates marks them for destruction by the 26S proteasome. The UPS is known to play a key role in almost all aspects of plant growth, development and stress response – for example, the perception of the majority of phytohormones is dependent on the UPS.
We investigate how plants use protein degradation as a signalling mechanism, and are especially interested in a specific branch of the UPS called the N-degron pathway (formerly N-end rule pathway).
The N-degron pathway
The N-degron pathway is an ancient and highly evolutionarily conserved proteolytic system that targets proteins for destruction based on the nature of their N-terminus (the beginning of the protein) (e.g. Gibbs et al., 2014 Trends in Cell Biology). Proteins are synthesised with an N-terminal Methionine, but in many cases new N-terminal residues are exposed by peptidases. N-terminal residues can be stabilising or destabilising; if the new N-terminal residue is destabilising, then the protein can be targeted for destruction via the N-degron pathway.
In previous work carried out in the lab of Prof. Michael Holdsworth (University of Nottingham), plant-specific ERFVII transcription factors were identified as the first physiological targets of the N-degron pathway in plants. Regulation of their stability via this pathway controls plant perception and response to low oxygen stress (hypoxia), a situation that frequently occurs during floods (Gibbs et al. 2011 Nature). Regulation of these transcription factors was also shown to mediate perception and transduction of nitric oxide (NO), an important developmental signalling molecule in plants (Gibbs et al., 2014 Molecular Cell).
We recently identified and characterised a new oxygen- and nitric oxide regulated target of the N-degron pathway - the polycomb repressive complex 2 (PRC2) subunit VERNALIZATION2 (VRN2) (Gibbs et al., 2018 Nature Communications), and we showed that this regulation is important for modualting growth and development (Labandera et al., 2021 New Phytologist) As part of the PRC2, VRN2 regulates the epigenetic repression of gene targets through methylation of chromatin. This suggests that the N-degron pathway is important for sensing and transducing oxygen and nitric oxide signals into direct transcriptional and long term epigenetic changes through targeting functionally distinct proteins to the same degradation pathway (ERFVIIs, VRN2). In work fuded by the ERC and the BBSRC we are now exploring how control of VRN2 stability is linked to its functions during a wide range of processes.
Rice flooding trials at IRRI, Philippines, 2013. The N-end rule pathway was recently shown to regulate the transcriptional response to low oxygen, which has important implications for the development of flood tolerance in crops.