# UV to blue neuronal phototransduction mechanisms

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $467,589

## Abstract

Many insects pose major health and economic hazards to humans as common disease vectors and
agricultural pests. Almost all of our present understanding of insect phototransduction is based on opsin-based
photoreception in eyes that mediate image forming vision. My lab has recently discovered two additional
phototransduction mechanisms in Drosophila. Cryptochrome (CRY) and Rhodopsin 7 (Rh7) expressed in central
brain neurons mediate rapid onset sustained electrophysiological responses in these neurons. CRY and Rh7
light signaling underlie a novel form of non-image forming vision that strongly modulates complex time-of-day
dependent insect behavioral responses to light, including avoidance/attraction behavioral choice between light
and shade and light evoked arousal. While CRY's mechanism of action is due to light evoked redox state
changes of its flavin adenine dinucleotide (FAD) chromophore and Rh7's mechanism of action is through a G-
protein signaling pathway, they physiologically interact and may form the basis of a true color vision system for
non-image forming vision that discerns specific light spectra. We have extended our study of non-image forming
vision to harmful nocturnal Anopheles gambiae and diurnal Aedes aegypti mosquitoes and find that CRY1s
mediate very distinct time-of-day dependent species specific behavioral light responses in these mosquitp-o
important disease vectors. Remarkably, nocturnal and diurnal mosquito CRY1s confer mosquito species specific
behavioral effects when expressed in all CRY expressing cells in a cry-null Drosophila genetic background and
nocturnal mosquito CRY1 is significantly more light sensitive than diurnal mosquito CRY1 measured by multiple
behavioral and electrophysiological assays. We will determine the detailed mechanisms that confer species
specific physiological and behavioral light responses for flies and mosquitoes and other insects using a highly
sensitive electrophysiological assay that we have developed that will allow us to accurately measure redox state
changes and biological outputs for light sensitive CRYs and functional interactions between CRYs and Rh7, in
combination with behavioral analysis. Our custom designed instrumentation allows us to examine CRY
spectrally driven redox state changes in vivo. Present insect control strategies rely heavily on highly toxic
pesticides. A far more environmentally friendly alternative is to make use of light-based behavioral manipulation
of insects in a species specific fashion to attract harmful insect species to traps or to repel them away from
human habitation. The goal of our research to form a rational basis for designing innovative new LED devices
for species-specific harmful insect control in the ongoing fight against vector-borne diseases.

## Key facts

- **NIH application ID:** 10818424
- **Project number:** 5R35GM127102-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Todd C Holmes
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $467,589
- **Award type:** 5
- **Project period:** 2018-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818424

## Citation

> US National Institutes of Health, RePORTER application 10818424, UV to blue neuronal phototransduction mechanisms (5R35GM127102-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10818424. Licensed CC0.

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