H2020Индивидуална стипендия2019–2021

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-09-01 → 2021-08-31
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Бактерията Bacillus subtilis се изследва чрез модели с червеи, за да се разбере как тя пречи на образуването на токсични протеинови струпвания при болестта Паркинсон. Разбирането на тези механизми може да помогне за създаването на нови методи за диагностика и терапия.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

In the past years, the collective community of microorganisms found in the human gut (the gut microbiome), has emerged as a new important player influencing Parkinson’s Disease (PD). Specifically, the composition of the gut microbiome was shown to differ between PD patients and healthy individuals and these differences correlate with the severity of the symptoms. Understanding the molecular mechanisms by which gut bacteria interact with the host to alter physiology in remote tissues, can lead to novel prognostic and therapeutic interventions for PD. However, how single species of the gut microbiome affect manifestations of the disease remains unclear. In people with Parkinson’s, the protein alpha-synuclein (α-syn) builds up and forms toxic clumps which induce the degeneration of specific dopamine-producing neurons. Using a worm model of PD expressing the α-syn, we tested the effect of commercially available probiotic bacteria in the formation of toxic protein aggregates. We identified a strongly protective effect when worms were fed the strain Bacillus subtilis PXN21 (isolated from Bio-Kult), in comparison to the regular worm’s diet. The main goal of this project was to study how this probiotic induces the protective effect, at the molecular level. We proposed to elucidate this by focusing on both organisms in the interaction: the bacteria and the worms. We aimed to explore the physiological changes induced by B. subtilis in the worms by studying the overall gene expression in the host. From the bacterial side, we proposed to identify specific genes and metabolic pathways used by B. subtilis to reduce protein aggregates by doing a single-gene deletion library screening.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

THE UNIVERSITY OF EDINBURGH · EdinburghКоординаторОбединеното кралство