Timothy Johnston

Role of Sulfiredoxin-1 in maintaining neuronal function and redox homeostasis

About me

I attended Cardiff University, completing an integrated Master’s degree in Neuroscience. For my Master’s project, I studied at the UK Dementia Research Institute (UKDRI) in the Peters/Smith/Van der Goes van Naters labs, investigating the contribution of Alzheimer’s Disease risk genes to glial regulation of neuron activity and synaptic transmission. I gained an appreciation for the use of Drosophila melanogaster as a model organism and an understanding of the importance of mammalian systems to validate findings. These factors, along with my passion for neuroscience research, led me to apply for this project in Dr. Sangeeta Chawla’s lab.

My project

Neurons are amongst the most metabolically-demanding cells in the body, producing reactive oxygen species (ROS) as a byproduct of oxidative phosphorylation. Large amounts of ROS can induce a state of oxidative stress (OS), which is implicated in the pathology of many neurodegenerative diseases. However, these also play a vital physiological role in controlling signalling pathways. Sulfiredoxin-1 (Srx) is an antioxidant enzyme that reduces hyper-oxidised typical 2-Cys Peroxiredoxin (Prx) enzymes, which allows for the recycling of these enzymes so that they can continually reduce peroxides. Srx is, therefore, likely to affect intracellular hydrogen peroxide levels that may modulate synaptic activity. The chaperone activities of Prx enzymes depend on their oxidation state too, which Srx is also likely to exert an effect over. Work at the University of York has shown that Srx is upregulated in response to neuronal activity and OS, via distinct MAPK signalling cascades. This up-regulation is protective against the loss of dendrites in neuron cell cultures under conditions of OS. We aim to elucidate the importance of Srx to neuron function and investigate the impact it has upon other putative substrates, which are yet to be characterised. I will perform experiments using Drosophila melanogaster and mammalian neuron cultures to understand the role of Srx in maintaining neuronal redox homeostasis.


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