Descripción del proyecto
Información sobre la organización de las membranas celulares
Las membranas celulares son estructuras complejas formadas por lípidos, proteínas e hidratos de carbono que actúan conjuntamente para crear una barrera con una permeabilidad selectiva que separa la célula de su entorno exterior. Aunque se conocen muy bien las propiedades y funciones de las membranas celulares, hoy en día se tienen pocos conocimientos sobre la organización de las membranas debido a las dificultades que plantea su estudio «in vivo». En el proyecto COMP-MICR-CROW-MEM, financiado por el Consejo Europeo de Investigación, se prevé utilizar la microscopía computacional avanzada para estudiar las interacciones entre los lípidos y las proteínas en parches de membrana complejos, mediante la imitación de las condiciones celulares reales. El objetivo del proyecto es desarrollar un marco para simular procesos biomoleculares, investigar la clasificación y agrupación de las proteínas y aportar conocimientos moleculares sobre membranas biológicas realistas.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
9712CP Groningen
Países Bajos