# Sonomagnetic Imaging and Sonomechanical Control of Biological Processes in Deep Tissues

> **NIH NIH R00** · RICE UNIVERSITY · 2021 · $247,514

## Abstract

Project Summary / Abstract
 New ways to observe and manipulate cellular function have revolutionized our understanding of biology.
Such methods have undergone multiple paradigm shifts in history, from Hooke's microscope and Cajal's
staining of neurons, to modern fluorescent imaging based on green fluorescent protein (GFP) and opsin-based
optogenetics. These modern genetically encoded methods, defined by their use of protein-based agents that
can be expressed by cells, provide key capabilities such as cell-specific targeted expression, continued
production in dividing cells, and coupling with state-of-the-art genetic engineering methods. However, as most
of these protein tools rely on optical interactions, they are fundamentally limited by the ~ 1 mm penetration
depth of light into opaque tissue. As the objects of study increase in size from cell cultures and translucent
organisms such as C. elegans, via small rodents, to human beings, this limitation becomes increasingly
severe. To overcome this technological challenge, I aim to develop next-generation methods that are both
genetically encoded and able to communicate with deeply penetrant forms of energy. In particular, I will
leverage the unique physical and biochemical properties of gas vesicles (GVs), a class of gas-filled protein-
only nanostructures discovered in certain photosynthetic microbes. In Aim 1, a new method, “sonomagnetic
imaging” (SMI), will be developed, which takes advantage of GVs' dual ability to induce contrast for magnetic
resonance imaging (MRI) and interact with ultrasound pulses for selective erasing of such contrast. In parallel,
a new method to control gene expression, sonomechanical control (SMC), will be developed in Aim 2 wherein
ultrasound pulses can collapse GVs and trigger signaling pathways to activate gene expression at high spatial
precision and low energy deposition. In Aim 3, I will integrate these novel methods to the task of engineering
spatiotemporally trackable and controllable mammalian gut microbes. The completion of these aims will
establish a platform for designing probiotics that can be monitored for their function and controlled externally by
clinicians to deliver therapies at precise locations and times. Furthermore, the invention of these technologies
will stimulate broad interest in other biomedical research that requires sensitive imaging and control of cellular
function in deep-lying tissues. The proposal also describes research expertise training, conference attendance
and the acquisition of leadership skills that, altogether, will prepare me as a competitive candidate to establish
an independent research program at a major research institute and stimulate advances towards my long-term
goal of developing imaging and control technologies to study intact biological systems.

## Key facts

- **NIH application ID:** 10267208
- **Project number:** 5R00EB024600-04
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** George J Lu
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $247,514
- **Award type:** 5
- **Project period:** 2020-09-21 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267208

## Citation

> US National Institutes of Health, RePORTER application 10267208, Sonomagnetic Imaging and Sonomechanical Control of Biological Processes in Deep Tissues (5R00EB024600-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10267208. Licensed CC0.

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