Project description
Building synthetic cells that sense and respond to force
Cells constantly sense and react to mechanical forces in their surroundings. This is a process known as mechanotransduction. While these mechanical signals are as vital as biochemical ones, they are much harder to control or replicate. The ERC-funded MechanoSynth project aims to create a synthetic system that allows cells to respond to force in new, programmable ways. Specifically, it will design cells that can activate specific genes in response to mechanical cues. As a proof of concept, MechanoSynth will reprogramme fibroblasts to modify their properties, movement, and the stiffness of their surrounding tissue, which are key features in diseases linked to abnormal tissue mechanics. The project will offer a new toolkit for cell engineering.
Objective
Our understanding of cell biology has reached the point in which cells can be exogenously engineered to carry out specific tasks. This is typically applied to generate gene circuits that respond to biochemical interactions between specific molecules. However, cells sense not only biochemical but also mechanical signals, in the process of mechanotransduction. Here, we propose to re-engineer cell mechanotransduction from scratch, in a manner that is not based on any endogenous cell signalling pathway. We will achieve this by harnessing our novel findings that force application to the cell nucleus regulates transport through nuclear pore complexes (NPCs), in such a way that proteins can be made to translocate to the cell nucleus with force by appropriately tuning their active and passive transport properties. First, we will implement a mechanosensing element, involving a precise understanding of the mechanical parameters regulating nucleocytoplasmic transport, and subsequent design of molecules with optimal mechanosensitivity (that is, force-dependent nuclear localization). Second, we will implement a control element, enabling a system to control to what extent, and for how long, force reaches the nucleus and triggers subsequent mechanosensing. Finally, we will implement a functional element, by which mechanosensitive molecules will be engineered to trigger the transcription of specific genes in the nucleus. As a proof-of-concept, we will apply this system to re-engineer three main properties of fibroblasts and mesenchymal cells (matrix remodelling, migration, and epithelial/mesenchymal plasticity), all involved in pathological responses to altered tissue mechanics. This project will deliver synthetic mechanotransduction, a novel tool that will be orthogonal and compatible with existing cell engineering approaches. Further, it will provide an answer to the fundamental question of how a functional, biological mechanotransduction system can be generated de novo.
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.
You need to log in or register to use this function
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
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-ADG
See all projects funded under this callHost institution
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.
08028 Barcelona
Spain
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.