Biophotonic nanoswitches
Recent mapping of all
physical interactions between proteins in a given
cell has confirmed the notion that interactions between proteins are
highly regulated and underpin all cellular processes. Researchers and
technologists have been presented with a major challenge - how to ask
specific questions of such complex systems especially when protein
interactions change with time in a given cell and result in different
end states.
For example when a human cell responds to stress, specific interactions
between master regulatory proteins start to drive a recovery process or
initiate a controlled commitment to cell death. This project aims to
generate a generic technology for solving this problem - introducing
synthetic switches into live cells that can 'fine-tune' protein
interactions by remote control. This exciting approach should allow the
investigator to programme changes in defined protein-protein
interactions by the introduction of small interfering molecules
engineered to be switched on and off by light of carefully selected
wavelengths.
Changes in the structure of a small molecule are triggered by
external
light pulses inducing conformational rearrangements in the peptide
backbone and hence alterations of the biological properties of the
Intracellular Biophotonic Nanoswitch (IBN). IBNs are light-sensitive
molecular structures linked to the short peptide sequences that
recognize features on the surface of a target/molecule that has been
targeted for switching. Conventional and novel methods for IBN delivery
into live cells will allow patterning of the swiches into populations
of cells.
Operating these IBNs by light will allow the researcher to
pattern the activation of switches in such complex cell populations or
to 'programme' the switching process in single cells - a step-forward
in the technology of manipulating master regulators of discrete
intracellular pathways.
Our proposal's adventure and risk relates to the problems of IBN design
and their potential for self-reporting in live cells. The exciting
prospect looms of gaining programmable photonic control over normal
physiology (directing stem cell differentiation, manipulating wound
healing and delaying cell senescence), neoplasia (cancer biology of
cell cycle checkpoint dysfunction and photonically-controlled
therapeutics), constructed cell communities (light-directed tissue
engineering) and molecular target identification (the search for new
medicines and products).
To visit our Intracellular Biophotonic Nanoswitches Group website,
click here.