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ERC

MEMBRANEFUSION Report Summary

Project ID: 648432
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - MEMBRANEFUSION (Structure and mechanism of viral and cellular membrane fusion machineries)

Reporting period: 2015-09-01 to 2016-12-31

Summary of the context and overall objectives of the project

Fusion of two biological membranes is essential to life. It is required during organism development, for trafficking of material between cellular compartments, for transfer of information across synapses, and for entry of viruses into cells. Fusion must be carefully controlled and the core fusion components are typically found within a complex regulatory machine. We are applying a combination of state-of-the-art cryo-electron tomography, image processing and correlative fluorescence and electron microscopy methods to obtain detailed structural information on assembled fusion machineries and of fusion intermediates both in vitro and in vivo. By determining how viral and synaptic fusion complexes reposition and restructure prior to fusion, how they arrange around the fusion site, how they reshape the membrane to induce fusion, and how these processes can be regulated and inhibited, we aim to derive a mechanistic model of membrane fusion in situ.
Regulated fusion between biological membranes represents a central function that is essential to life. We do not, however, understand how assembled fusion machineries and membranes interact and move to drive this process. By contributing to this understanding, this project will deliver fundamental knowledge on an important, basic biological process.
Influenza A and HIV-1 are major human pathogens, and the fusion of these viruses with the host cell is a target for drug development and a process interfered with by neutralizing antibodies. By contributing to understanding of this process, this project will deliver data that may be valuable in the design and development of strategies for disease treatment or prevention.
It is challenging to obtain detailed structural information on biological systems in situ within complex environments. This project will help develop methods to do this.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

At this early stage in the project, we have hired project staff, established experiments, data collection protocols and image analysis pipelines. We have reconstituted membrane fusion in vitro for both influenza virus and synaptic vesicle fusion, and have generated preliminary cryo-electron microscopy images that will help us to understand aspects of the mechanism of membrane fusion. We have also collected cryo-electron microscopy images of HIV-1 from which we are deriving new information on the arrangement of the matrix protein layer that underlies the viral membrane.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project is at too early a stage to reliably assess the impact. Nevertheless, our preliminary data suggest that we will be able to derive new knowledge of membrane fusion mechanisms, and thereby obtain a deeper understanding of mechanisms of virus infection and of synaptic transmission. We will also improve methods and techniques that can be applied in other research projects.
Record Number: 198287 / Last updated on: 2017-05-18
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