# Imaging cell-type-specific transcription in living mammalian brain

> **NIH NIH R35** · HUNTER COLLEGE · 2021 · $390,000

## Abstract

Gene expression is a fundamental problem at the core of life science. All cells in an adult organism contain an
identical set of genes, but their expression varies widely depending on the context, such as cell type and
environmental queues. Transcription is the critical first step in gene expression, which is intricately controlled
by complex regulations and the disruption is pathogenic for many diseases. Much knowledge about the
mechanism has been gained using fixed cells and sequencing assays. Nonetheless, we still do not understand
how the variability of transcription is regulated in living mammals, dynamically in space and time, as the animal
performs development, physiology, and cognitive tasks such as learning. In particular, the role of the cis-
regulatory elements (i.e., enhancers) plays in the context-dependent transcriptional dynamics is obscure. Here
we will develop technology for addressing the current bottleneck. Over the past years, our laboratory has
advanced methods for visualizing transcriptional dynamics in the brain of live mouse (‘intravital MS2
technology’). Single molecules of mRNA of a gene of interest have been imaged in a specific cell type by
intravital multiphoton microscopy (MPM), revealing previously unknown properties of nascent transcripts in
vivo. For the next five years, we will demonstrate more versatile intravital MS2 technology geared toward the
functional annotation of the genome. Taking inspirations from the prior success of illuminating the structure and
function of the neuronal network in vivo, we will fuse intravital MPM, smart molecular sensors, and genomic
engineering to dissect the function of the transcriptional regulatory network in live murine brains. Our research
will lay a foundation for unraveling the origin of diverse cell types, plasticity, and neurodegenerative disorders
of the mammalian brain.

## Key facts

- **NIH application ID:** 10166076
- **Project number:** 1R35GM140841-01
- **Recipient organization:** HUNTER COLLEGE
- **Principal Investigator:** Hyungsik Lim
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2021-08-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166076

## Citation

> US National Institutes of Health, RePORTER application 10166076, Imaging cell-type-specific transcription in living mammalian brain (1R35GM140841-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10166076. Licensed CC0.

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