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


Project Description

The electrical activity of neurons is metabolically demanding and generates
reactive oxygen species (ROS) through mitochondrial oxidative
phosphorylation. ROS can initiate signaling events to modulate neuronal
firing but persistent ROS is detrimental. Neurons therefore neutralize ROS
through activity-dependent expression of antioxidant proteins to control
spatiotemporal features of ROS signals and maintain homeostasis. ROS and
oxidative damage accumulate during aging such that neuronal activity-
induced antioxidant responses are not sufficient to maintain optimal neuronal
function and neuronal viability, contributing to age-related cognitive decline.
It is therefore important to understand how neurons counter ROS. We and
others have shown that in response to synaptic activity and imposed
oxidative stress, neurons upregulate expression of the antioxidant gene
Sulfiredoxin-1 (Srxn1). This PhD project aims to understand the relative
contribution of Srxn1 in maintaining neuronal redox homeostasis and its
importance for neuronal structure and function.

The student will use various genetic and pharmacological tools including
CAS9/CRISPR to perturb Srxn1 expression in cultured mammalian neurons
and in Drosophila. The effect of Srxn1 depletion (or overexpression) on
neuronal structure, neuronal ROS burden and synaptic function will be
assessed using cellular, biochemical and electrophysiological techniques.

Funding Notes

This studentship is fully funded for four years and covers: (i) a tax-free annual stipend at the standard Research Council rate (£15,009 estimated for 2020 entry), (ii) research costs, and (iii) tuition fees at the UK/EU rate.

References

Entry requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this research project means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions.

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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