Optogenetics: From molecules to applications

Scientific case and aim

In the past two decades, genetically encoded fluorescent proteins such as GFP have revolutionized the life sciences by enabling observation of cellular processes through fluorescence microscopy. Generalizing the concept of genetically encoded probes, a newly emerging field called ‘optogenetics’ is utilizing photoreceptor proteins to directly control cellular processes and organism behavior with light in a non-invasive, reversible, and spatiotemporally precise manner.

Biology has always been mainly an observational science. Yet, to determine mechanisms and networks that underlie complex biological processes, merely observing the process is not enough: true understanding arises from systematic manipulation of parameters (perturbation) and subsequent analysis of the system response. Optogenetics offers that opportunity in an unprecedented way by allowing precise control of cellular processes in space and in time. To achieve such control, novel customized light-regulated actuators are emerging in which photosensor protein domains that respond to the desired light quality are combined with effector protein domains that deliver the desired biological activity. Despite these successes, there remains a clear demand for robust and generic strategies to achieve optogenetic control. In addition, combining optogenetics with multicolor imaging has remained a challenge due to the overlapping spectral requirements. Finally, the true potential of optogenetics for the study and modulation of complex biological processes in intact model organism has not been fully explored.

The new field of optogenetics spans fundamental molecular research all the way to cell biology, physiology and neuroscience. This workshop will bring together research leaders that work in the various disciplines that collectively form the optogenetics field. One important objective of the workshop will be to bring the (slowly) emerging Dutch optogenetics community in contact with international research leaders. The workshop will be considered a success if the researchers from the various disciplines in the end form a more closely knit community that will catalyze collaborations in order to achieve 1) more fundamental insight into photoreception and signal transduction, 2) improved strategies to obtain optogenetic control, 3) novel biological insight through application of optogenetic strategies in advanced model systems. To stimulate discussions and interactions and to drive true innovation, the workshop is organized around the following three Grand Challenges.

1.       Everything under control – defining generic strategies for optogenetic control.

a.       Defining generic strategies for generating light-sensitive enzymes.

b.      Strategies to cage enzymes or ligands using photosensitive domains

2.       Seeing more - photoreceptor engineering and advanced instrumentation

a.       Combining imaging with optogenetics

b.      Understanding and altering the spectral properties of photosensitive modules

3.       Enlightening life – light-sensitive tools in advanced model systems and in the clinic

a.       Optogenetic strategies for model organisms and humans

b.      Chemooptogenetics.