Award details

Membrane nanotubes as a novel mechanism for intercellular communication

Reference	BB/C512896/1
Principal Investigator / Supervisor	Professor Daniel Davis
Co-Investigators / Co-Supervisors
Institution	Imperial College London
Department	Biological Sciences
Funding type	Research
Value (£)	224,806
Status	Completed
Type	Research Grant
Start date	01/06/2005
End date	31/05/2008
Duration	36 months

Abstract

The concept that immune surveillance is sometimes facilitated by the assembly of an immunological synapse triggered a wave of research in imaging immune cell interactions and much discussion on the similarity of intercellular communication controlling disparate biological processes. Analogous to very recent observations in neural cells, we have recently observed another unexpected mechanism for intercellular communication between immune cells. Cultured PC12 rat neural cells or kidney cells could be connected via membrane nanotubes perhaps related to cytonemes in the Drosophila wing imaginal disc. Applying single photon-excitation resonance scanning confocal microscopy to image immune cell interactions in vitro, we observed such nanotubes between live immune cells. These initial micrographs are in press for the Cutting Edge section of J Immunol and here we propose a thorough investigation into the biophysical nature of membrane nanotubes and how they may play a role in intercellular communication. An important first achievable goal is to thoroughly characterise membrane nanotubes between various cell-cell couples. For many different types of immune cell interactions we will determine the frequency of nanotube formation, the energy and cytoskeletal requirements for nanotube formation, and perhaps most excitingly which cell surface and intracellular components may transfer between cells via membrane nanotubes. These parameters will be measured using our unique resonance-scanning single photon excitation confocal microscope for imaging immune cell interactions. We will then proceed to investigate whether or not specific signals could propagate down membrane nanotubes, for example if specific phosphorylation states of key proteins can be seen within membrane nanotubes that are in contact with stimulating cells. One approach to carry this out will be to use fluorescence lifetime imaging (developed in previous BBSRC-funded research) to report fluorescence transfer betweenGFP-tagged receptors and a genetic anti-phosphotyrosine mAb. We will also determine whether or not bacteria and viruses may spread between cells via membrane nanotubes. In summary, this proposal aims to lead the basic research necessary to postulate, and test for, functions for membrane nanotubes and the supracellular structures that they create.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	Immunology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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