Project description
Moss piglets and their disordered proteins may help us respond to environmental stressors
For more than a century, protein function was thought to be very closely related to the complex three-dimensional (3D) structure resulting from the folding process, and this structure was considered to be largely immutable. In the last couple of decades, intrinsically disordered proteins (IDPs) have been turning that idea on its head. Recent estimates suggest that at least 15 % of proteins lack a fixed 3D structure under physiological conditions yet carry out important functions. Tardigrades, microscopic members of the animal kingdom also known as water bears or moss piglets, have IDPs that form glass-like solids, enabling these little guys to survive desiccation for up to a decade or longer. The EU-funded FLINDIP project is studying tardigrades and their IDPs for insight into how IDP genotypes relate to phenotypes. This work could point to ways to combat stressors and enhance the fitness of plants and animals in the coming years.
Objective
Mapping genotype to phenotype is a key problem of protein physics, evolutionary biology, biotechnology and medical genetics. In this project, we plan to focus on intrinsically disordered proteins, a large group of proteins whose genotype-phenotype connection is poorly understood. Such proteins do not adopt a unique native structure. Instead, they explore numerous conformations depending on external conditions. Recent bioinformatic analyses show that up to 15% of all proteins are intrinsically disordered.
The critical role of intrinsically disordered proteins in cellular functions and in the onset of pathological conditions generated significant interest for their study. Much effort has been devoted to map the effects of particular mutations on protein functionality. However, no attempt to systematically study the genotype-to-phenotype link in intrinsically disordered proteins has been made. Obtaining such information is essential for sharpening theoretical models of protein folding and molecular evolution, as well as for de novo design of intrinsically disordered proteins with improved activities.
The aim of this project is to experimentally measure and analyse, for the first time, the genotype-to-phenotype connection for several intrinsically disordered proteins by deep mutational scanning. We plan to focus on tardigrade proteins which are essential for their ability to survive complete desiccation. We plan to generate libraries of cells expressing hundreds of thousands of variants of these proteins and to perform competition assays to measure functionality of every variant in the library. We will then use a variety of approaches to analyse the dataset, including machine-learning algorithms to model the fitness of variants and to design new functional intrinsically disordered proteins.
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 biological sciences evolutionary biology
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- natural sciences biological sciences genetics mutation
- natural sciences computer and information sciences artificial intelligence machine learning
- natural sciences biological sciences molecular biology molecular evolution
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
SW7 2AZ London
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.