MicroSPARK · A Single-Molecule Technology for Resolving Chaperone Action in Neurodegenerative Diseases
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-04-01 → 2021-03-31
- Финансиране от ЕС
- 212 934 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите на протеините-шаперони, като Hsc70, се анализират чрез нови технологии за наблюдение на единични молекули. Това помага за разбирането на болести като Алцхаймер и Паркинсон, при които се образуват вредни протеинови агрегати в организма.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
A Single-Molecule Technology for Resolving Chaperone Action in Neurodegenerative Diseases
The Marie Skłodowska Curie Action “A Single-Molecule Technology for Resolving Chaperone Action in Neurodegenerative Diseases” (project acronym: MicroSPARK) was devoted to advance our technological capabilities of studying misfolding processes in neurodegenerative diseases and elucidate mechanisms of chaperone action and drug action. This was achieved through the first-time combination and integration of single molecule and microfluidics technologies, and their use in dissecting the action mechanism of chaperones. Neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are increasingly prevalent disorders of our ageing society. These diseases arise from the formation of amyloidogenic protein aggregates. Molecular chaperones can counteract aggregate formation, but their molecular action mechanisms remain poorly understood. This Marie Skłodowska Curie Action addresses this challenge and implements the µSPARK technology to extend our understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and introduces new means to sense amyloidogenic species for the development of therapeutics against neurodegenerative disease. The core advancement of this project is the implementation of microfluidic sorting devices with single molecule detection to address important questions related to protein misfolding diseases with a specific focus on chaperones and diagnostics. Specifically, microfluidic diffusional sizing combined with confocal fluorescence spectroscopy was used to study the disaggregation mechanism of the Hsc70 heat shock protein machinery. Moreover, free-flow electrophoresis was used in combination with laser-induced spectroscopy to resolve heterogeneities of oligomeric species created during aggregation reactions. In addition, the technological capabilities of the platform were used to establish a new diagnostic technology termed digital immuno-sensing assay (DigitISA).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
A range of debilitating neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, arise from the formation of amyloidogenic protein aggregates. Molecular chaperones can counteract aggregate formation, but their molecular action mechanisms remain poorly understood. This is chiefly due to the fundamental challenge of resolving heterogeneous and dynamic aggregating protein species in the presence of chaperones. In order to address this challenge and to advance our knowledge of chaperone action, I propose establishing µSPARK, a novel technology that will allow, for the first time, the unravelling of the detailed microscopic mechanisms by which chaperones target and disassemble amyloidogenic protein species in heterogeneous mixtures at the single-molecule level. These new insights will become possible through the first-time combination and seamless integration of two advanced technologies: (i) Miniaturized fluidic sorting devices and (ii) single-molecule fluorescence spectroscopy combined with three-colour coincidence detection. This will enable high-throughput single-particle interrogation of individual chaperone–aggregate complexes providing fundamentally new means for understanding key aspects of chaperone function. To demonstrate the new possibilities, µSPARK will be exploited to unravel the action mechanisms of heat-shock proteins in curtailing amyloid-β peptide and α-synuclein aggregation. This will provide new insights into proteostatic regulatory mechanisms in Alzheimer’s and Parkinson’s disease. The µSPARK technology will then be exploited to dissect—with high throughput and single-particle resolution—the molecular action mechanisms of small-molecule modulators that promote the inhibitory function of chaperones on protein aggregation. This will allow identifying new strategies to ameliorate aggregate toxicity and will pave the way for µSPARK to become a novel screening tool for drug development.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз