Optogenetics is the combination of genetic and optical methods to control specific events in live cells with high temporal and spatial precision. In 2010, optogenetics was chosen as the Method of the Year across all fields of science and engineering by Nature Methods. Two methods for the photocontrolled activation of apoptosis in cancer cells will be contrasted; one that relies on the development of externally administered biophotonic nanoswitches and the second, in which the photocontrolled agents are genetically integrated in the cell. The intrinsic apoptosis pathway is regulated by the interaction of pro- and anti-apoptotic members of the Bcl-2 family of proteins. These interactions are mediated through highly conserved α-helices and corresponding grooves. The design, synthesis and characterization of intracellular biophotonic nanoswitches (IBNs) derived from Bcl-2 helices will be discussed. The conformation of these peptides and hence their activity in vitro and in vivo can be controlled with external light pulses. IBNs can be used in live cells to control apoptosis in a UV light-dependant manner. IBNs offer a novel research approach for the reversible modulation of protein interactions in real time within live cells but their use requires them to cross cellular membranes. Hence in an optogenetic approach LOV-domains, light-sensing domains present in many photo-reactive proteins, are engineered to target Bcl-xL and influence cell cycle arrest and cell death in a biomimetic manner. This work will deliver novel generic tools with the potential for the study and the manipulation of many biological processes and potentially with therapeutic applications.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: Declaration of Funding: EPSRC-Basic Technology EP/F040954/1.