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Biophotonic Nanoswitches

15 June 2010

The BBC Website has highlighted work from the group of Professor Rudolf Allemann in the School of Chemistry. This project, carried out in collaboration with Professor Paul Smith and Dr Rachel Errington (Cardiff Medical School), Dr Arwyn Jones (Welsh School of Pharmacy) and Professor Huw Summers (School of Engineering, University of Swansea) and funded by a £1.4M grant from EPSRC, may one day reveal how cancer cells survive attempts to kill them, as well as providing a method for differentiating stem cells leading to the development of methods for growing replacement organs.

Biophotonic nanoswitches are made from a light sensitive molecule and a short peptide segment taken from key proteins that control the longevity of cancer cells. When a pulse of light hits the switch, it changes its shape to an active form that is able to bind target proteins within a cell, triggering or shutting down a chemical process, including those processes that keep tumour cells growing.

In describing this work, Professor Allemann said "Proteins only have a function when they adopt a well-defined 3D structure. The cell is a thick soup of proteins, with rather extensive, uniform and shallow surfaces that are difficult to target with conventional small molecule based drugs. We try to target these protein surfaces using peptides taken from natural proteins that should allow us to control protein-protein interactions. This is chemistry at work; based on a fundamental physical understanding of biological chemistry, we use simple chemical building blocks to control the complex biochemical machinery inside a cell.”

These nanoswitches are designed to selectively target two of the processes that keep cells healthy. These pathways, regulated by critical proteins called Bcl-2 and p53, control processes such as cell division and cell survival. Aberrations in the regulation of these pathways account for a large number of tumors. With the right peptides, it might become possible to effectively switch off a tumour cell simply by applying a pulse of light.

"The early success with tumour cells suggests that the approach may be more widely applicable," said Dr Errington.

"Our biophotonic nanoswitches have applications in all areas where we would want to switch a molecular process on or off or change the fate and direction of a pathway," she said.

If proteins that cause cells to change their fate could be controlled in this way, then a pattern of light pulses could transform a uniform sheet of stem cells into tissues containing an ordered array of different cell types - a stepping stone to growing replacement organs.

Biophotonic nanoswitch in its unactivated state (top-left). A pulse of light (top-right) induces a conformational change in the switch (bottom-right) and the attached peptide so that the nanoswitch is able to effectively bind to its cellular target.

Biophotonic nanoswitch in its unactivated state (top-left). A pulse of light (top-right) induces a conformational change in the switch (bottom-right) and the attached peptide so that the nanoswitch is able to effectively bind to its cellular target.

http://gow.epsrc.ac.uk/ViewGrant.aspx?GrantRef=EP/F040954/1

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