# High-throughput integrated live imaging and optogenetic pacing platform to assess hypoxia responsiveness in the fly heart

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $547,286

## Abstract

Project Summary
Ischemic preconditioning is a well-established phenomenon, in which a brief episode(s) of controlled ischemia
and reperfusion renders cardioprotection from a subsequent sustained episode of ischemia. An emerging body
of evidence demonstrated that neural regulated heart rate modulation confers cardiac preconditioning
responses. Understanding the mechanism through model systems of preconditioning would help us identify the
genes and proteins when designing future drug targets for the prevention of ischemic cardiac injury. As a
promising alternative to electrical pacing to modulate heart rate, optogenetic pacing does not require physical
contact, has high spatial and temporal precision, offers more specific excitation, and avoids artifacts from
electrical stimulation. Recent developments in the field of optogenetics make it possible for non-invasive and
specific optical control of the heart rhythm in animal models, such as in Drosophila melanogaster. Drosophila is
a powerful genetic model system that has been used since the early 1900s to characterize genes associated
with human diseases, including cardiac diseases. Studies performed in flies can provide insights into conserved
mechanisms in cardiac diseases, which can be applied to higher organisms, including humans. Working in
collaboration with Drs. Airong Li and Rudolph Tanzi from the Massachusetts General Hospital, we demonstrated
non-invasive optogenetic pacing and concurrent optical coherence tomography (OCT) imaging of the Drosophila
heart for the first time. Recently, we further demonstrated red-light optogenetic pacing and successful optical
control of tachycardia, bradycardia, and restorable cardiac arrest in fly models. Building on the decade-long
productive collaboration with Drs. Li and Tanzi and new collaborations with Dr. Abhinav Diwan (cardiologist)
and Dr. Jeanne Nerbonne (cardiac electrophysiologist) and Dr. Kenneth Schechtman (biostatistician) at
Washington University, we propose to develop a high-throughput integrated OCT imaging and dual-color
optogenetic pacing system and establish a novel research platform to study preconditioning and hypoxia
responsiveness in the fly heart. We hypothesize that periods of bradypacing will precondition the fly heart to
protect against hypoxia, via activation of the autophagy-lysosome pathway. The specific aims are: 1) Develop
and optimize a high-throughput integrated instrument for non-invasive OCT imaging and optogenetic control of
fly heart function in vivo; 2) Develop double transgenic fly models and functional assays based on OCT imaging
to characterize fly heart physiology in vivo; 3) Define functional and molecular changes in response to hypoxia
and optogenetic preconditioning in transgenic fly models. If successful, the high-throughput optical imaging and
dual-color optogenetic pacing platform developed in this program combined with powerful double transgenic fly
models will enable us to characterize changes of the fly h...

## Key facts

- **NIH application ID:** 10318214
- **Project number:** 5R01HL156265-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Chao Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $547,286
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318214

## Citation

> US National Institutes of Health, RePORTER application 10318214, High-throughput integrated live imaging and optogenetic pacing platform to assess hypoxia responsiveness in the fly heart (5R01HL156265-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10318214. Licensed CC0.

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