Decrypting the Cryptochrome with Margaret Ahmad and Brian Crane

Margaret Ahmad and Brian Crane, in collaboration with Frontiers in Plant Science, Frontiers in Physiology, and Frontiers in Chemistry, have launched a new Research Topic showcasing research on the cryptochrome, a blue light receptor first discovered in plants.

Margaret Ahmad and her colleagues characterized the plant cryptochrome in Arabidopsis thaliana, and the protein has since been found to have a range of crucial roles in different organisms. In 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey Hall, Michael Rosbash and Michael Young for their pioneering work on the Drosophila circadian clock in which the cryptochrome is a central component. The circadian clock coordinates organisms’ daily rhythms and thus regulates key functions such as behavior, metabolism, hormone levels, and sleep. It was Margaret’s vision to connect scientists from different disciplines all researching cryptochromes to share knowledge, encourage collaboration, and gain new insights into this essential gene. 

De-Crypting Cryptochromes: Electromagnetic Field Sensors and Clockwork for Quantum Biology and Medicine is open for submissions

Poppy Russell, Journal Specialist for Frontiers in Plant Science, recently spoke with Margaret about her research on the cryptochrome and the importance of connecting scientists between fields.

Poppy Russell: What is the cryptochrome and why is it so named?

Margaret Ahmad: Cryptochromes are a class of flavoprotein receptors that absorb blue light. Classical photobiology experiments from over a hundred years ago, including some conducted by Charles Darwin, had provided physiological evidence of a specific blue light photoreceptor. It was suggested to be a flavoprotein but no one could identify it. The term cryptochrome was originally coined by John Gressel (in 1979) to denote the ‘cryptic’ nature of this mysterious receptor.

PR: Since the discovery of the cryptochrome gene, the cryptochromes are found to have essential roles in many different organisms. Do the cryptochromes play similar roles across taxa?    

MA: Cryptochrome proteins are highly structurally conserved, such that light triggers similar primary biochemical reactions in all cryptochromes. Nonetheless, the downstream physiological responses mediated by cryptochromes vary greatly; in plants, cryptochromes control practically all aspects of growth and development in response to blue light, whereas in vertebrates, they are central components of the circadian clock and possibly function in bird navigation. There appear to be a few evolutionarily ancient functions, such as stress responses and entrainment of the circadian clock, which are conserved across phylogenetic lines.

PR: What is the importance of cryptochrome in circadian rhythms and the Nobel prize-winning research?

MA: One of the most exciting developments was the discovery, in 1998, that cryptochromes transmit blue light information to entrain the Drosophila clock by interacting directly with the core clock proteins. This work originated from the labs of Jeff Hall, Michael Rosbash, and Michael Young, who received the Nobel Prize in 2017 for their work on the genetics and characterization of the Drosophila circadian clock. In 1999, a critical role of cryptochrome was also found in the mammalian clock, where Gilbertus van der Horst showed that a cryptochrome knockout mouse lacked clock function, and the cryptochrome interacts with central mammalian clock proteins. These discoveries have placed cryptochromes squarely into the field of medicine and the onset of disease because the circadian clock controls so many core physiological functions.

PR:  Why do you think it is important to bring together research on cryptochromes across different fields?

MA: All cryptochromes are virtually structurally identical to photolyases, a rare class of DNA repair enzymes that respond to light. Thanks to prior work of Aziz Sancar, who obtained the Nobel prize in Chemistry (2015) for his characterization of the enzymatic properties of photolyases, it has been possible to characterize the photochemistry and physical properties fundamental to all cryptochromes at the receptor level. This means that, in principle, external light and/or electromagnetic field cues can be used to manipulate cryptochrome responses across phylogenetic lines. The field is, therefore, on the cusp of developing a whole new technology.

However, as outlined above, cryptochromes have vastly different physiological roles in different organisms, which involve many distinct downstream signalling intermediates and integration with other cellular pathways in complex ways. Only the physicists can suggest quantum signals; only the chemists can provide mechanisms for impact on receptor function; and only the biologists and medical specialists can apply these insights meaningfully to manipulate their particular systems. 

In sum, effective communication across disciplines is essential for the development of a whole new technology with far-reaching consequences that can only be vaguely imagined at this point. 

PR:  What is the next big question for research on the cryptochrome?

MA: The fundamental question in the field today is mechanistic: how do cryptochromes respond to electromagnetic fields? This will unlock new doors into research on magnetoreception in bird navigation and the potential to manipulate cryptochromes using magnetic fields in human therapy and crop breeding.