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Gut_Fights_PD SIGNED

Investigating protective mechanisms of gut bacteria in C. elegans models of Parkinson’s disease

Total Cost €

EC-Contrib. €

Partnership

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Gut_Fights_PD project word cloud

Explore the words cloud of the Gut_Fights_PD project. It provides you a very rough idea of what is the project "Gut_Fights_PD" about.

model symptoms diseases alpha nematode understand protein strategies species preliminary beneficial proposing interaction patients pd syn parkinson modulate probiotic manipulating bidirectional paradigm effect lab deficits connection genetically nervous neurodegenerative bacterial aggregation tractable neuroprotective severity unbiased alterations metabolic protective models data neurodegeneration influence molecular candidate discovered worm mechanisms uncover clear gap host reveal nature elicit throughput human strategy prognostic correlate motor therapeutic bacteria compounds composition players metabolites act neurological microbiota gastrointestinal discovery employed elegans single pharmacological disease mechanistically elucidate synuclein frequently shift protect view gut interact stages

Project "Gut_Fights_PD" data sheet

The following table provides information about the project.

Coordinator	THE UNIVERSITY OF EDINBURGH Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL website: www.ed.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	United Kingdom [UK]
Total cost	183˙454 €
EC max contribution	183˙454 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2017
Funding Scheme	MSCA-IF-EF-ST
Starting year	2019
Duration (year-month-day)	from 2019-09-01 to 2021-08-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	THE UNIVERSITY OF EDINBURGH THE UNIVERSITY OF EDINBURGH Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL website: www.ed.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (EDINBURGH)	coordinator	183˙454.00

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Project objective

The recent discovery that the composition of the gut microbiota can influence the symptoms of neurodegenerative diseases is a paradigm shift in how we view these conditions. In Parkinson’s disease (PD), patients frequently experience gastrointestinal symptoms years before the development of motor deficits and recent studies reveal clear alterations in the gut microbiota composition at advanced stages, which correlate with severity of their symptoms. Therefore, understanding the molecular mechanisms by which gut bacteria interact with the host to affect the nervous system may uncover novel prognostic and therapeutic strategies for neurological diseases. To address this gap of knowledge, we propose a single bacteria-worm model as a genetically tractable system to mechanistically investigate the connection between bacterial metabolites produced in the gut and neurodegeneration. Preliminary data from the lab on a protein aggregation model of PD in C. elegans, show a strong protective effect of a human probiotic bacterial species on α-synuclein aggregation, a well-established factor in Parkinson’s disease. The aim of this project is to understand the mechanisms through which the probiotic bacteria act to protect from α-syn aggregation and the nature of the response induced in the nematode. We are proposing a bidirectional strategy, manipulating genetically both players in this interaction, the bacteria and the nematode. Using a candidate molecular approach based on available data and an unbiased high-throughput analysis, we expect to elucidate new metabolic pathways employed by the bacteria to modulate protein aggregation as well as the molecular mechanisms that elicit this response in the nematode. By directly testing on various C. elegans models of PD the pharmacological effect of the discovered beneficial metabolites, we will identify specific neuroprotective compounds with future therapeutic potential.

Publications

List of publications.
year	authors and title	journal	last update
2020	MarÃa Eugenia Goya, Feng Xue, Cristina Sampedro-Torres-Quevedo, Sofia Arnaouteli, Lourdes Riquelme-Dominguez, AndrÃ©s Romanowski, Jack Brydon, Kathryn L. Ball, Nicola R. Stanley-Wall, Maria Doitsidou Probiotic Bacillus subtilis Protects against Î±-Synuclein Aggregation in C.Â elegans published pages: 367-380.e7, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.12.078	Cell Reports 30/2	2020-02-06

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