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How protective signals from the gut modify neuronal activity and behaviour, using C. elegans as a model system.


Project Description

Amyloid protein misfolding leading to loss of neuronal function are fundamental pathogenic mechanisms of numerous age-associated neurodegenerative diseases, including Alzheimer’s (AD). A fascinating fundamental challenge is to understand how signals from peripheral organs, such as the gastrointestinal tract, can influence the progression of amyloid protein misfolding in the nervous system. Work in the van Oosten-Hawle lab found that activation of transcellular stress responses in the C. elegans gut can protect against amyloid protein aggregation and toxicity in neuronal cells. It is however currently not known which neuronal microcircuit responds to these protective signals from the intestine by an altered signalling activity and how this modifies neuronal behaviour that could exacerbate organismal protection. This project combines molecular biology, behavioural studies, data analytics and computational modelling to identify 1) neuronal subtypes affected first by amyloid proteins (a-syn, amyloid beta, tau) as a function of age; 2) how neuronal signalling activity is protected by stress responses induced in the gut and 3) how this correlates with behavioural changes by measuring subtle differences in worm locomotion using artificial intelligence approaches. The work will provide exciting new insight into protective mechanisms initiated from the gut that can prevent loss of neuronal function.

For informal enquiries please contact:

Please see following links for more information:

http://www.vanoostenhawlelab.com

http://www.astbury.leeds.ac.uk/people/staff/staffpage.php?StaffID=POH

http://www.fbs.leeds.ac.uk/staff/profile.php?un=fbspv


Funding Notes

View Website DEADLINE 01/04/20

View Website DEADLINE 01/06/20

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

References

O’Brien, D., Jones, L., Good, S., Miles, J., Aston, R., Smith, C., Vijayabaskar, S., Westhead, D., and van Oosten-Hawle, P. (2018) A PQM-1-mediated response mediates transcellular chaperone signaling and organismal proteostasis. Cell Reports. 2018 Jun 26;23(13):3905-3919

Miles, J., Scherz-Shouval R., and van Oosten-Hawle, P. (2019) Expanding the organismal proteostasis network: Linking systemic stress signalling with the innate immune response. Trends in Biochemical Sciences, 2019 Jul 11. pii: S0968-0004(19)30142-2

van Oosten-Hawle, P., Porter, R.S., and Morimoto, R. I. (2013). Regulation of organismal proteostasis by transcellular chaperone signaling. Cell 153, 1366-1378

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

FTE Category A staff submitted: 60.90

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

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