Thiol Dioxygenases and Oxygen Sensing in Plants
Plants are subjected to a wide range of environmental and biological stresses. These include flooding, a problem which is increasing with the advent of climate change. Flooding is a major cause of crop damage across the globe, often with devastating socio-economic consequences. Coupled with a rapidly increasing population, it is clear that finding ways to make plants more flood-tolerant is a major challenge in the effort to sustain food security. As biochemists, we can help address this challenge by understanding how plants respond at the molecular level to being flooded. We can then try to manipulate these responses to help plants survive for longer when they become submerged.
The molecular response to flooding has recently been uncovered and found to be dependent on oxygen availability, something which decreases when plants are submerged. In low oxygen conditions, a signalling pathway is activated which directs a plant to turn on flood-survival mechanisms. The plant must be able to sense how much oxygen is present so that it knows when to turn this signalling pathway on or off. It does this with oxygen-sensing enzymes, called Plant Cysteine Oxidases.
The Plant Cysteine Oxidases catalyse the oxidation of N-terminal cysteine residues on target proteins, but only in the presence of sufficient oxygen. This oxidation triggers the degradation of these proteins, which are conversely stabilised in low oxygen, initiating low-oxygen signalling and adaptation. We are interested in how the Plant Cysteine Oxidases interact with their target proteins and oxygen, both so we can fully uncover how oxygen signalling works in plants but also to engineer these enzymes to enhance low-oxygen signalling and improve plant flood tolerance.
Redox Stress in Plants
Abiotic stress can result in an oxidative burst that generates reactive oxygen species (ROS) in plant cells. Since the sulfhydryl groups on cysteine side chains are particularly susceptible to oxidation, abiotic stress could therefore trigger oxygen-sensing signalling pathways in a non-enzymatic manner. ROS and other redox stress-related species can also have a wider range of impacts on plant cells, ranging from stress-signalling to non-specific cellular damage.
We are interested in understanding how ROS and other redox-active molecules impact on plant cells, in particular on low oxygen signalling events. An important aspect of this is on being able to quantify redox markers in cells and we are working as part of a large interdisciplinary team, funded by EPSRC, developing tools to do this, with our focus being on measuring redox markers in plant cells.
Thiol Dioxygenases and Oxygen Sensing in Humans
In collaboration with the Licausi lab (Pisa, Italy) and the Ratcliffe lab (NDM), we found that a thiol dioxygenase in humans (ADO) is similar to the Plant Cysteine Oxidases in that it regulates the stability of certain proteins with N-terminal cysteine residues in an oxygen-dependent manner, meaning it is a novel oxygen sensor in humans. We are now investigating the role of ADO in more detail to understand the role it plays in hypoxic disease states.