Project description
Cracking the ‘tubulin code’ in an innovative animal model
Microtubule arrays play a plethora of roles in cell division, cell shape, intracellular transport and motility. Despite being highly conserved, the protein tubulin exists in many different isoforms and post-translational modifications further increase diversity. This complex ‘tubulin code’ modulates microtubule structure, dynamics and function over large spatial and temporal scales. The code has yet to be ‘cracked’, telling scientists how it guides function from the molecular to the organism scale and over an organism’s lifetime. The ERC-funded TubulinCode project aims to answer many of these open questions by combining techniques in biochemistry, cell biology, physiology and introducing a novel fish model for lifelong in vivo imaging.
Objective
Microtubules (MT) are core components of the eukaryotic cytoskeleton with essential roles in cell division, cell shape, intracellular transport, and motility. Despite their functional divergence, MTs have highly conserved structures made from almost identical molecular building blocks tubulin proteins. A variety of posttranslational modifications (PTMs) diversifies these building blocks, which is thought to control most of the properties and functions of the MT cytoskeleton, a concept referred to as the tubulin code.
While they appear to have subtle effects at the molecular level, tubulin PTMs are essential for maintaining cellular functions of MTs over large spatial and temporal scales. Yet, a comprehensive knowledge of the principles of the tubulin code, connecting its functions across the molecular, cellular and organismal levels, is almost entirely lacking.
Our project aims to obtain a novel molecular and mechanistic understanding of how tubulin PTMs control long-term cellular function and homeostasis. Our unique approach bridges all relevant scales of biology and relies on a synergy between our powerful experimental models and expertise in biochemistry, structural biology, single-molecule assays, systems-biophysics, cell biology, and physiology.
Specifically, we will: (1) Determine how different tubulin PTMs affect biophysical and structural properties of MTs and their interactions with associated proteins; (2) Define the impact of tubulin PTMs on overall MT cytoskeleton behaviour and the resulting physiological implications in neurons; (3) Combine zebrafish and mouse models and develop a novel fish model for lifelong in-vivo imaging to determine how the tubulin PTMs control lifelong MT-based functions.
Our work will define the importance of tubulin PTMs by revealing their critical molecular functions over the lifetime of an organism. The project has the potential to substantially change our perception of the cytoskeletons role in homeostasis and disease.
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 biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology homeostasis
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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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
HORIZON-ERC-SYG - HORIZON ERC Synergy Grants
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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-2022-SYG
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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.
75794 PARIS
France
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