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Subcellular Lipid Atlas: Decoding Organelle Identity with Targeted Lipid Profiling

Project description

Mapping membrane lipids with high resolution

Cell membranes are built from lipid bilayers and they protect cells and control nutrient migration by acting as selective barriers. They also contain proteins that facilitate cell communication and define the function of cellular organelles. Membrane lipid composition helps organelles maintain organisation, communicate and adapt to changing cellular demands. Despite their importance, organelle lipidomes remain poorly understood because lipids are highly dynamic and difficult to analyse with spatial and temporal precision. The ERC-funded LipID project will develop a chemical biology strategy to profile lipids at the level of individual organelles in living cells. The idea is to design photoactivatable lipid probes to identify endogenous lipids with high resolution and determine membrane identity.

Objective

Organelle identity, defined by membrane and protein composition, is crucial for maintaining cellular organisation, functions and communication pathways. Disruption of organelle identity can lead to cellular dysfunction and severe health issues, such as fatty liver disease, cardiovascular diseases and lipid storage disorders. Although it is known that lipids are a hallmark of membrane identity, we still have a limited understanding of organellar lipid compositions. Particularly since lipids are very dynamic through transbilayer movement, local metabolism and lipid transfer between organelles, which requires a high temporal resolution to capture. While existing methods are effective for protein analysis, lipid profiling at the organelle level remains challenging.
To answer the outstanding question of how organellar lipidomes shape organelle function, we propose an innovative chemical biology approach for organelle-specific lipid profiling. We will label the lipids of individual organelle membranes in vivo and determine their chemical identity and concentration by lipidomic profiling. We will first design and synthesise functionalised lipid probes for distinct organelles, allowing for their release and photo-crosslinking to endogenous lipids. By analysing the labelled lipids, we will acquire a precise and detailed lipid profiles of individual organelles, and furthermore characterise the lipidome of specific suborganellar membrane domains. This will allow us to define the organelle membrane identity of the major organelles with unprecedented spatial and chemical resolution. Such data will provide the much-needed basis to connect organelle identity and maintenance with function and the research community with open access, high-resolution lipid maps. This has the potential to change the way we think about biological membranes on a fundamental level, advancing not only our understanding of organelle function, but setting the stage to study its impact on health and disease.

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HORIZON-ERC - HORIZON ERC Grants

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(opens in new window) ERC-2025-STG

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Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution

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.

€ 1 500 000,00
Address
BATIMENT CE 3316 STATION 1
1015 LAUSANNE
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 1 500 000,00

Beneficiaries (1)

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