Signaling, Deconstructed: Using Optogenetics to Dissect and Direct Information Flow in Biological Systems

Abstract

Cells receive enormous amounts of information from their environment. How they act on this information—by migrating, expressing genes, or relaying signals to other cells—comprises much of the regulatory and self-organizational complexity found across biology. The “parts list” involved in cell signaling is generally well established, but how do these parts work together to decode signals and produce appropriate responses? This fundamental question is increasingly being addressed with optogenetic tools: light-sensitive proteins that enable biologists to manipulate the interaction, localization, and activity state of proteins with high spatial and temporal precision. In this review, we summarize how optogenetics is being used in the pursuit of an answer to this question, outlining the current suite of optogenetic tools available to the researcher and calling attention to studies that increase our understanding of and improve our ability to engineer biology. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Signalling dynamics, cell decisions, and homeostatic control in health and disease

“…Notably, optogenetics ( Figure 3 c) – the capability to control biochemical reactions by light – is proving to be extremely powerful in probing biochemical networks [ 69 , 70 , 71 , 72 ]. For example, Wilson et al.…”

Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation

“…Although such rapid stimulus-response experiments have been traditionally difficult to perform in vivo, the recent advent of optogenetic perturbations and live biosensors of gene expression offer the possibility to dissect gene expression networks with unprecedented resolution (Figure 1e-f) [6][7][8][9][10] .…”

Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation

“…Differences in response kinetics can also distinguish direct interactions (e.g., where a transcription factor directly regulates its target’s expression) from indirect links (where an intermediate gene product must first be synthesized), which can be crucial when the input influences a downstream gene through multiple regulatory paths. Although such rapid stimulus-response experiments have been traditionally difficult to perform in vivo , the recent advent of optogenetic perturbations and live biosensors of gene expression offers the possibility of defining transcriptional input/output relationships with unprecedented resolution ( Figures 1E and 1F ) ( de Mena et al, 2018 ; Farahani et al, 2021 ; McFann et al, 2021 ; Patel et al, 2019 ; Rullan et al, 2018 ).…”