# Quantitative analysis of the biological forces and their context in tissue patterning

> **NIH NIH R35** · COLD SPRING HARBOR LABORATORY · 2020 · $480,000

## Abstract

Rules specifying form and function of an organism are encoded in the genome. Over the years, a
variety of approaches have been leveraged to elucidate the underlying programs and machinery that govern
the size and form of different organs or structures. These include genetic strategies, employed to identify gene
products that control developmental events, and biochemical advances that have provided molecular insights
into how communication between individual cells during development is accomplished. While information
theory and mathematical modeling have made inroads toward integrating genetic and molecular aspects of
development, these approaches are fundamentally limited by the simple fact that most measurements that
guide these applications (either genetic or biochemical) are often derived from experimental contexts that lack
the spatial or temporal richness found in vivo. 
 My research team is prepared to address a theoretical, quantitative, and computational program at Cold
Spring Harbor Laboratory (CSHL) with an emphasis on in vivo cellular imaging and in situ sequencing
technologies for gene expression and cell lineage analysis during development. During my postdoctoral
training, I developed an in situ RNA sequencing technology that can be generally employed to determine the
spatial and informational heterogeneity of gene expression in a genome-wide manner. As an independent
investigator I have adapted this technology to monitor gene expression in developing tissues. These methods
enable the simultaneous measurement of gene expression patterns in thousands of single cells in the context
of a developing cell lineage. While simple in concept, this major advance will allow dynamic and temporal
changes in gene expression to be directly tied to three-dimensional architecture, enabling the mathematical
modeling of key developmental processes in the absence of prior limitations.
 Initially, we will focus on understanding how oscillations in gene expression pattern, including those
mediated by the cell cycle, modulate growth factor signaling. Specifically, we will determine if cyclical patterns
of gene expression are sufficient to generate a morphogenic field that controls the size and shape of
developing structures or how these patterns contribute to the robustness of these processes in vivo. We will
also determine the molecular mechanisms of gradient-associated transcriptional initiation/elongation using
direct RNA sequencing in situ. Both oscillatory gene expression and morphogen gradient-associated
transcriptional initiation/elongation impact aspects of cell fate commitment stem cells (important in tissue
regeneration and homeostasis) and these approaches can be used to dissect the contribution of multiple
genetic pathways in vivo. In summary, we have the conceptual framework, biological questions, cutting-edge
technologies, and rigorous scientific environment to better characterize the biological forces driving tissue
patterning and developmen...

## Key facts

- **NIH application ID:** 9938627
- **Project number:** 5R35GM119772-05
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** Je Hyuk Lee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $480,000
- **Award type:** 5
- **Project period:** 2016-08-19 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938627

## Citation

> US National Institutes of Health, RePORTER application 9938627, Quantitative analysis of the biological forces and their context in tissue patterning (5R35GM119772-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9938627. Licensed CC0.

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