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Characterization the role RNA interaction in TDP-43 protein dynamic in neurons

  • Full or part time
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

RNA-binding proteins (RBPs) play an important role in the neuronal system.
Dysregulation of RBPs caused by cellular stress or disrupted protein
homeostasis leads to protein aggregation with consequent damage to
neurons. One of such RBP, TDP-43, has a high propensity to form
aggregates observed in neurons of ageing and neurodegenerative
conditions. Under basal conditions, TDP-43 shuttles between the nucleus
and cytoplasm, transporting target RNA molecules to neuronal extensions
for further processing or local translation. When cells are stressed, TDP-43
brings its target RNAs into an organelle called a stress granule where they
are protected from degradation during stress. We have recently reported a
novel mutation in TDP-43 which abolishes RNA interaction and enhances
TDP-43 protein aggregation. This result and a few other recent studies
indicate that the interaction with RNA plays an important role in keeping
TDP-43 protein soluble, but the mechanism of which is still yet clarified. To
follow up the characterization of the RNA-binding deficient TDP, this project
will address the following key questions:
- Is RNA-binding deficiency affecting other TDP-43 protein characteristics
such as stability and trafficking?
- Can RNA-binding deficient TDP-43 aggregates be refolded by traditional
chaperone pathway?
- What are cellular consequences caused by the loss of RNA-binding of
TDP-43?

This project will examine the properties of TDP-43 across a range of
biological levels, from in vitro protein analysis to cellular models, using
biochemical and biophysical analyses to characterize protein solubility, self-
association and structural changes under different conditions and advance
imaging to track protein movement.

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)

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