# Illuminating molecular mechanisms of cellular functions by single-molecule and super-resolution imaging

> **NIH NIH R35** · HARVARD UNIVERSITY · 2021 · $417,542

## Abstract

Project Summary / Abstract
Understanding the mechanisms of cellular function and their dysfunction in disease requires a detailed picture
of the molecular interactions in cells. In particular, it is desirable to have imaging tools with single-molecule
sensitivity, molecular-scale resolution, and genome-scale capacity to allow direct visualization of these
molecular interactions and to probe the collective behaviors of different genes and gene products that give rise
to cell and tissue function. The long-term research goal of my laboratory is to develop advanced fluorescence
imaging methods that meet these demands and to apply these methods to elucidate molecular mechanisms of
cellular functions that are of both fundamental and medical significance.
In the next five years, we propose to focus our NIGMS-funded research mainly in the following two directions.
(1) To understand the structure and function of a novel cytoskeletal structure in neurons. Our NIGMS-
supported research on the development and application of super-resolution STORM imaging has led to the
discovery of a periodic membrane-associated cytoskeleton structure in neurons, primarily in axons. While we
have a basic model of the ultrastructural organization of some key components of this structure, including
actin, spectrin and associated molecules, we expect many additional protein components to be present in this
structure. These components and their structural organization remain to be determined. Our understanding of
the functional roles of this novel structure is also far from complete. We propose to use super-resolution
imaging in conjunction with other methods to determine the protein components and structural organization of
this periodic skeleton structure, and to investigate its functional roles in axon morphogenesis and
synaptogenesis, action potential generation and propagation, axon degeneration, and other axonal functions.
(2) To investigate the spatial organization of chromatin and chromosomes important for gene regulation. The
spatial organization of chromatin plays an important role in many essential genome functions such as gene
expression regulation, DNA replication, repair and recombination. In particular, many features of the chromatin
conformation have been implicated in gene regulation, such as open and closed chromatin states, promoter-
enhancer interactions, topologically-associated domains, and chromosome territories. Misregulation of
chromatin structures has been implicated in a variety of diseases. However, many gaps remain in our
understanding of the three-dimensional (3D) organization of chromatin and chromosomes. Our NIGMS-
supported research on STORM imaging and chromatin remodeling studies allowed us to develop a super-
resolution chromatin imaging approach and reveal novel chromatin organizations. We will advance our
chromatin/chromosome imaging capability by developing the ability to trace the 3D path of the chromatin chain
in the chromosome and to stu...

## Key facts

- **NIH application ID:** 10136624
- **Project number:** 5R35GM122487-05
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** XIAOWEI ZHUANG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $417,542
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136624

## Citation

> US National Institutes of Health, RePORTER application 10136624, Illuminating molecular mechanisms of cellular functions by single-molecule and super-resolution imaging (5R35GM122487-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10136624. Licensed CC0.

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