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Computational Microscopy of Crowded Membranes

Project description

Insight into cell membrane organisation

Cell membranes are complex structures that consist of lipids, proteins and carbohydrates which work together to create a selectively permeable barrier that separates the cell from its external environment. Although there is significant knowledge regarding the properties and functions of cell membranes, our current understanding of membrane organisation is limited due to the challenges of studying them in vivo. Funded by the European Research Council, the COMP-MICR-CROW-MEM project plans to use advanced computational microscopy to study lipid-protein interactions in complex membrane patches, mimicking real cellular conditions. The project aims to develop a framework for simulating biomolecular processes, investigate protein sorting and clustering, and provide molecular insights into realistic biological membranes.

Objective

Cell membranes form a highly complex and heterogeneous mixture of membrane proteins and lipids. Understanding the protein-lipid interplay that gives rise to the lateral organisation principles of cell membranes is essential for life and health. Thus, investigations of these crowded membranes is emerging as a new and exceptionally exciting frontier at the crossroads of biology, life sciences, physics, and chemistry.

However, our current understanding of the detailed organisation of cellular membranes remains rather elusive. Characterisation of the structural heterogeneity in-vivo remains very challenging, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatio-temporal resolution. In recent years, computer simulations have become a unique investigatory tool for understanding the driving forces governing the lateral organisation of cellular membrane components and this “computational microscopy” has become indispensible as a complement to traditional microscopy methods.

In this ERC project I will, using advanced computational microscopy, study the interaction of lipids and proteins in complex, crowded, membrane patches, to enable the driving forces of membrane protein sorting and clustering to be unravelled at conditions closely mimicking real cellular membranes. The specific objectives are:

• To develop a novel computational microscopy framework for simulating biomolecular processes at multiple resolutions.
• To use this new computational microscopy framework to investigate the driving forces of membrane protein sorting and clustering.
• To provide a molecular view of realistic, crowded, biological membranes composed of hundreds of different lipids and proteins.

The outcomes will enable subsequent studies of many different types of cell membranes based on forthcoming lipidomics studies and progress in structural characterisation of membrane proteins.

Host institution

RIJKSUNIVERSITEIT GRONINGEN
Net EU contribution
€ 2 396 584,57
Address
Broerstraat 5
9712CP Groningen
Netherlands

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Region
Noord-Nederland Groningen Overig Groningen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 2 396 584,57

Beneficiaries (1)