# Near-Infrared Fluorescent Proteins, Biosensors and Optogenetic Tools

> **NIH NIH R35** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $441,176

## Abstract

ABSTRACT
Near-infrared light is favorable for imaging in mammalian tissues due to low absorbance of hemoglobin,
melanin and water. Therefore, fluorescent proteins, biosensors and optogenetic constructs for optimal imaging,
optical readout and light manipulation in mammals should have fluorescence and action spectra within the
near-infrared window. Interestingly, natural bacterial phytochromes utilize the low molecular weight biliverdin,
found in most mammalian tissues, as a photoreactive chromophore. Due to their near-infrared absorbance
bacterial phytochromes are preferred templates for designing optical molecular tools for applications in
mammals. Based on the analysis of the photochemistry and structure of bacterial phytochromes we suggest a
variety of possible bacterial phytochrome-based fluorescent proteins, biosensors, and optogenetic tools. The
design strategies and experimental considerations for such probes are proposed. Near-infrared fluorescent
proteins and biosensors will extend the methods developed for conventional microscopy into a deep-tissue in
vivo macroscopy including multicolor cell and tissue labeling, fluorescence resonance energy transfer, cell
photoactivation and tracking, and detection of enzymatic activities and metabolites in tissues. The near-infrared
optogenetic tools will allow noninvasive light-control of biochemistry and physiology of a living animal directly
through the skin. Moreover, all bacterial phytochromes-based reagents will spectrally complement existing
genetically encoded probes in the visible range. The planned probes also will expand our basic knowledge of
photochemistry and light-induced signaling of phytochromes in nature. Availability of the near-infrared probes
will further stimulate the development of novel in vivo imaging and light-manipulation technologies, optimization
of strategies for gene delivery to specific cells and tissues in vivo, design of targeted noninvasive illumination,
and refining optical readouts. Overall, this will result in a wide range of noninvasive studies of chemical and
metabolic status, as well as molecular and cellular interactions in intact tissues and whole living mammals.

## Key facts

- **NIH application ID:** 9929596
- **Project number:** 5R35GM122567-05
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Vladislav Verkhusha
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $441,176
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929596

## Citation

> US National Institutes of Health, RePORTER application 9929596, Near-Infrared Fluorescent Proteins, Biosensors and Optogenetic Tools (5R35GM122567-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9929596. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*