# Optogenetic toolkit for precise control of organellar calcium signaling

> **NIH NIH R21** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $225,702

## Abstract

Endoplasmic reticulum (ER), or sarcoplasmic reticulum in muscle cells, acts as the largest intracellular
Ca2+ store and plays a pivotal role in shaping the spatiotemporal dynamics of Ca2+ sigals to maintain
intracellular Ca2+ homeostasis. Reciprocally, calcium is also intimately involved in regulating ER functions,
including lipid synthesis, protein synthesis, folding, modifications and translocation. Consequently, the
ER employs a series of regulators to control Ca2+ concentration on both sides of the membrane and
mediate Ca2+ transfer with the surrounding organelles via membrane contact sites. Deregulated ER Ca2+
homeostasis not only results in ER stress and unfolded protein response (UPR), but also is involved in
cardiovascular diseases, neurological diseases, metabolic syndromes and other diseases.
Pharmacological modulation and genetic manipulations are often applied to study the ER Ca2+ handling
machinery, but these largely irreversible approaches often lack spatial precision and specificity.
 Optogenetics technology provides a novel approach for modulating ER Ca2+ homeostasis with
superior spatiotemporal resolution and high reversibility. Hence, the team proposes to create an
innovative optogenetic toolkit, named as Genetically Encoded ER Calcium Actuators (GEECAs), that
enable optical interrogation of ER Ca2+ homeostasis, ER-organelle Ca2+ communications and organellar
Ca2+-modulated activities in multiple biological systems. In Specific Aim 1, the team will design a set of
GEECAs based on ER-localized calcium channels and/or their photoswitchable actuators to photo-tune
ER Ca2+ signals with varying kinetic and dynamic properties. In Specific Aim 2, the team seeks to develop
an optogenetic platform to control inter-organellar tethering and Ca2+ transfer between ER and its
surrounding organelles. The successful execution of this project will provide novel opportunities to
achieve noninvasive and precise modulation of ER Ca2+ homeostasis and inter-organellar Ca2+ signaling
with high spatiotemporal precision, thereby exerting remote control over cellular physiology, including ER
stress, energy metabolism, autophagy and mTOR signaling. From a translational perspective, molecular
tools generated from this project will provide novel interventional approaches for human diseases
associated with aberrant ER Ca2+ signaling.

## Key facts

- **NIH application ID:** 10388807
- **Project number:** 1R21GM145063-01
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Guolin Ma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $225,702
- **Award type:** 1
- **Project period:** 2022-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388807

## Citation

> US National Institutes of Health, RePORTER application 10388807, Optogenetic toolkit for precise control of organellar calcium signaling (1R21GM145063-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10388807. Licensed CC0.

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