UCI-led study reveals non-image light sensing mechanism of circadian neurons in fruit flies

Irvine, CA – November 7, 2019 – University of California, Irvine researchers reveal how an ancient flavoprotein response to ultra violet (UV), blue and red light informs internal circadian processes about the time of day.

The study, led by Todd C. Holmes, PhD, a professor in the Department of Physiology and Biophysics at the UCI School of Medicine, is titled, “Distinct mechanisms of Drosophila CRYPTOCHROME mediated light-evoked membrane depolarization and in vivo clock resetting,” and was published in Proceedings of the National Academy of Sciences. 

Phototransduction is relatively well characterized in the eyes and other external photoreceptors in animals for image-forming vision.  Much less understood are phototransduction mechanisms in non-eye photosensitive cells, including central brain neurons.  In the UCI School of Medicine-led study, researchers revealed how blue and ultra violet (UV) light create a sustained light response which is key to a form of non-image-forming vision that averages environmental light levels to determine the time of day and inform internal circadian processes.  Red light evokes a light response but less sustained.

“Image-forming vision works so rapidly that humans and likely other animals perceive the visual world as a continuous process,” said Holmes.  “Our eyes capture moment to moment changes in light that enable us to see objects and movement, even when moving from bright to dark surroundings.  An entirely different type of vision, the non-image-forming vision, is important for informing us about the time of day, based on the color and intensity of light.  It is a slower visual process that captures an average of light levels rather than moment to moment changes in light.”

Using Drosophila melanogaster, commonly known as fruit flies, researchers discovered that non-image-forming vision in invertebrates relies on redox chemistry of a light sensitive protein called Cryptochrome.  Biological redox chemistry is typically associated with metabolism.

“The protein ancestors of Cryptochromes were ultraviolet light-activated DNA repair enzymes that appeared in evolution well over 3 billion years ago before the appearance of our present day oxygen rich atmosphere that protects us from harmful ultraviolet radiation.  These first light sensing mechanisms evolved when single cell organisms developed the ability to repair their DNA damaged from UV light after coming too close to the surface of water.  At that time, there was no life on land.  It is remarkable that this ancient form of non-image forming vision persists to the present day.” 

Light is the primary regulator of circadian rhythms and evokes a wide range of time-of-day specific behaviors. By gaining an understanding of how insects respond to short wavelength light, researchers hope to develop new, environmentally friendly alternatives to controlling harmful insects, such as mosquitoes and flies, and reduce the need for toxic pesticides.

This study was funded by the National Institute of Health and an individual NSF Graduate Research Fellowship award.  This new research builds on the Holmes lab’s previous studies at the UCI School of Medicine published over the past few years in Science, Nature and Proceedings of the National Academy of Sciences. 

About the UCI School of Medicine

Each year, the UCI School of Medicine educates more than 400 medical students and nearly 150 PhD and MS students. More than 700 residents and fellows are trained at the UCI Medical Center and affiliated institutions. Multiple MD, PhD and MS degrees are offered. Students are encouraged to pursue an expansive range of interests and options. For medical students, there are numerous concurrent dual degree programs, including an MD/MBA, MD/MPH, or an MD/MS degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Program in Medical Education for Leadership Education to Advance Diversity-African, Black and Caribbean (PRIME LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.