Award details

Imaging magnetic micro- and nanoparticle-mediated activation of mechanosensitive transmembrane ion channels

Reference	REI18446
Principal Investigator / Supervisor	Professor Jon Dobson
Co-Investigators / Co-Supervisors	Professor Alicia El Haj
Institution	Keele University
Department	Sch of Medicine
Funding type	Research
Value (£)	32,548
Status	Completed
Type	Research Grant
Start date	01/04/2003
End date	30/09/2003
Duration	6 months

Abstract

The research will focus primarily on the remote activation of mechanosensitive (ie stretch-activated) transmembrane ion channels in human and mouse cell lines (eg primarily human osteoblasts, chondrocytes, atrocities). Remote activation will be accomplished via coupling of biocompatible magnetic micro- and nanoparticles to the cell membrane via RGD and integrin receptors as well as to tagged sites on the ion channel protein TREK-1. Mechanosensitive ion channels are present in a variety of human cells and the possibility of selectively activating them both in vivo and ex vivo would represent an extraordinary opportunity to advance our ability to control and monitor cellular processes. It would also present avenues for advances in targeted drug delivery and allow the directed activation of biochemical reaction pathways which are dependent on the operation of these channels. Such stress-initiated biochemical cascades are important for the formation and functional bone and connective tissue in bioreactors, however, the methods for applying the required stresses to activate the ion channels has not been achieved. The primary method for analysis of ion channel activation will be through confocal laser scanning microscopy imaging. This technique will allow us to monitor ion flux - particularly calcium but also potassium via the use of membrane potential-sensitive dyes - in response to magnetic activation. The ability to manipulate these ion channels from outside the body would be a significant scientific breakthrough with applications in therapeutics and tissue engineering and repair. This research has recently been funded by a Sir Henry Wellcome Showcase Award to the investigators from the Wellcome Trust. The purchase of a confocal system will also facilitate other fluorescent imaging research efforts within our Centre. These projects include the development of magnetic micro- and nanoparticle-mediated cell seeding of biodegradable scaffolds for tissue engineering/bioreactor applications; the development of imaging methods using novel engineered circulatory permuted Green Fluorescent Protein (cpGFP) and investigations of the effects of radiofrequency (RF) electromagnetic emissions on calcium flux in cells (funded by an industry grant from DiAx/Sunrise Telecommunications, Switzerland).

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Research Equipment Initiative 2002 (REI) [2002]
Funding Scheme	X – not Funded via a specific Funding Scheme

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