Emily Flashman

Photo of Emily Flashman

Dr Emily Flashman

Senior Research Fellow 

 

 

 

Research Interests

My research focusses on enzymes that sense and signal for stress, predominantly in plants. We investigate the structural and functional features of these enzymes that allow them to perform their functions, then try to find ways to manipulate their activity to improve stress tolerance. We work closely with biologists to enable us to implement our findings into cells and organisms.

Plant Cysteine Oxidases

Much of our focus is on the Plant Cysteine Oxidases, which are oxygen-sensing thiol dioxygenases that are important in molecular responses to flooding. They catalyse the oxidation of Cysteine at the N-termini of target proteins to Cys-sulfinic acid, triggering the degradation of these proteins via the N-degron pathway. Key substrates of the Plant Cysteine Oxidases are transcription factors which drive adaptive responses to the low oxygen experienced upon flooding. The oxygen-sensing properties of the Plant Cysteine Oxidase therefore connect the availability of oxygen with the physiological adaptations submergence. Our kinetic analyses identified that the Plant Cysteine Oxidases can act as plant oxygen sensors, and our structural studies of these enzymes have revealed important catalytic features at their active sites. Using our mechanistic, kinetic and structural knowledge of these enzymes, we are finding ways to manipulate Plant Cysteine Oxidase activity to improve submergence tolerance whilst still maintaining a healthy and productive plant.

Redox Stress in Plants 

Elevated reactive oxygen species (ROS) arises as a result of a number of stresses in plants, including low oxygen. 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. This includes collaborating with colleagues in the Dept. Chemistry to use redox-sensing probes to quantify redox markers in plant cells. 

Thiol Dioxygenases in Humans

In collaboration with colleagues from the University of Pisa and the Nuffield Department of Medicine in Oxford, we identified that a thiol dioxygenase in humans (Cysteamine Dioxygenase) is homologous 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.

Biography

 

Emily Flashman is a Senior Research Fellow and Associate Professor in Oxford Chemistry. She leads a research group investigating enzymes involved in stress-sensing, with a particular focus on oxygen-sensing enzymes in plants and their role in flood tolerance and other forms of hypoxic stress. This is supported by an ERC Consolidator Grant and previously a BBSRC New Investigator Award. From 2010-2016 Emily held a Royal Society Dorothy Hodgkin Fellowship and prior to this conducted postdoctoral research with Prof. Chris Schofield in Oxford Chemistry conducting kinetic and mechanistic studies on oxygen-sensing enzymes in humans. She gained her B.Sc. in Biochemistry at the University of Southampton and then conducted her D.Phil. in the Department of Cardiovascular Medicine in Oxford with Prof. Hugh Watkins, using biophysical methods to investigate the effects of Hypertrophic Cardiomyopathy-causing mutations on the interactions between proteins in heart muscle. Emily’s work has been recognised with a L’Oreal For Women in Science Fellowship (2011) and the 2018 University of Kent Wain Award for Excellence in the Biosciences.

Publications

Contact

emily.flashman@chem.ox.ac.uk
01865 275920

Research group

Flashman Group

College

Reuben College