# VISUALIZATION OF SUBCELLULAR DYNAMICS IN MULTICELLULAR ORGANISMS

> **NIH NIH R35** · BOSTON CHILDREN'S HOSPITAL · 2020 · $442,500

## Abstract

Abstract
Contemporary fluorescence microscopy connects our understanding of molecular events from
biochemistry and structural biology with their activities in living cells. Lattice light sheet microscopy
(LLSM) has made it possible for us to track phenomena such as endocytic vesicle assembly or lipid
kinase recruitment across an entire cell with high resolution, in both space and time, and with nearly
single-molecule sensitivity. Development during the past year of lattice light sheet microscopy with
adaptive optics (AO-LLSM) has overcome the optical limitations that have so far restricted most
studies to individual cells in culture, allowing us to achieve comparable resolution and sensitivity in the
complex optical environment of an intact, living, multicellular organism. It promises to bridge the gap
between cells and organisms, through high sensitivity, volumetric imaging, with diffraction-limited
resolution, of living tissues and developing embryos. We propose a research program in three
overlapping stages: implementation of AO-LLSM (in collaboration with its developer), development of
the new kinds of visualization and analysis software required by the scale and complexity of the
datasets, and use of AO-LLSM to solve a problem in vertebrate development. To meet the
computational challenges of analyzing the 4D data sets (from low signal-to-noise, the often non-
punctate characteristics of the objects being studied, the temporally varying spatial complexity of the
data, and the size of the data sets), we will develop new approaches using deep learning and related
algorithms, with consultation from experts. As a paradigm application, we will study the consequences
of Notch signaling and the related membrane-traffic and protein translocation events for cell
differentiation in zebrafish early neurogenesis. AO-LLSM will for the first time allow us to relate
molecular signaling events occurring on a timescale of seconds at cell interfaces to the ultimate fate of
daughter cells many hours later. We therefore expect that in the course of resolving some long-
standing issues in cell fate determination, we will develop microscopy approaches and computer
visualization tools that are widely applicable to a range of model systems and biological questions.

## Key facts

- **NIH application ID:** 9872183
- **Project number:** 5R35GM130386-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** TOMAS KIRCHHAUSEN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,500
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872183

## Citation

> US National Institutes of Health, RePORTER application 9872183, VISUALIZATION OF SUBCELLULAR DYNAMICS IN MULTICELLULAR ORGANISMS (5R35GM130386-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872183. Licensed CC0.

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