Project description
How protein clusters form
Proteins, the fundamental building blocks of life, bind together to form functional complexes. However, in certain cases, they can form aberrant complexes that have dramatic consequences for biological systems and are implicated in neurodegenerative disorders. Conventional approaches to understanding the formation of protein clusters have been challenging as the formation of protein clusters results in aggregates of different sizes and properties and correspondingly diverse effects on the function of living cells. The EU-funded DiProPhys project will address this challenge through a combination of microfluidics and single-molecule spectroscopy, creating a novel digital biophysics platform for studying protein aggregation. Using this approach, DiProPhys will be able to study aggregates one by one, inside and outside cells, and discover the fundamental physical factors that govern their formation and effects on the cellular systems.
Objective
Proteins are the fundamental building blocks of life, underpinning functional processes in living systems. They are able to exert their biological activities by binding to other proteins to form functional complexes which act as the machinery of life. In certain cases, however, proteins escape cellular quality control mechanisms and form aberrant complexes. The formation of such clusters stabilised by inter-molecular hydrogen bonds, amyloid aggregates, has dramatic consequences for biological systems and they are implicated in neurodegenerative disorders. The fundamental biophysical chemistry governing the formation of protein clusters has been challenging to probe and understand as this process results in a highly heterogeneous distribution of aggregates of different sizes and with different properties, and correspondingly diverse effects on living cells’ function. As such, conventional bulk methods are challenging to apply to uncover a fundamental biophysical understanding of their formation, dynamics and behaviour. The present proposal addresses this fundamental problem by bringing together microfluidics and single molecule spectroscopy to develop a novel digital biophysics platform for studying protein aggregation. Through this route, we will be able to study aggregates one by one, inside and outside cells, and discover the fundamental physical determinants that govern their formation and effects on the cellular systems. This proposal is motivated by the hypothesis that the physico-chemical properties of protein aggregates modulate their biological activity, and by studying protein aggregation at the level of single aggregates and single cells, we will access fundamentally new biophysical chemistry, including how liquid-liquid phase separation can modulate the nucleation barriers in protein aggregation, what the molecular mechanisms are by which amyloid aggregates can self-multiply, and what physical parameters determine their effects on living cells.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences physical sciences classical mechanics fluid mechanics microfluidics
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences biophysics
- natural sciences physical sciences optics spectroscopy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2020-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
CB2 1TN CAMBRIDGE
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.