# Architecture and Dynamics of a Gene Regulatory Network Controlling Cell Fate

> **NIH NIH F32** · DUKE UNIVERSITY · 2020 · $64,926

## Abstract

Project Summary
Cell fate acquisition is a fundamental developmental process in all multicellular organisms and a growing body
of evidence indicates that gene regulatory networks (GRNs) play an important role. However, the molecular
regulation of the entire pathway from stem cell to differentiation has never been defined for any tissue. The
Arabidopsis root, with its simple structure and defined stem cell niche, is a tractable model for studying the
transcriptional regulation of cell fate. Over two decades of work have outlined the GRN that orchestrates cell
proliferation and specification of the endodermis, a tissue analogous to the mammalian epithelium. This GRN is
mapped in sufficient detail to now mathematically model its dynamics. However, crucial questions remain
regarding downstream differentiation events. These include what regulators control endodermal fate stabilization
and differentiation? And how closely are such regulators connected to the transcriptional events controlling stem
cell proliferation? Until recently, technological constraints made it very difficult to study the molecular dynamics
underlying development of a single cell type in the context of an entire organ or organism. The research proposed
here utilizes new advances in imaging and transcriptional profiling to study protein and gene expression
dynamics at cellular resolution. The overall goal of this proposal is to expand the topology of the endodermal
GRN and begin to quantify the dynamics underlying differentiation. To achieve this goal, the proposed specific
aims include conducting a forward genetic screen in a sensitized genetic background to uncover novel regulators
of endodermal identity (Aim 1). In parallel, single cell RNA-sequencing experiments will define gene cascades
underlying cell maturation events, thus providing systems-level insight into regulation of the entire pathway from
stem cell to differentiated endodermis (Aim 2). To experimentally quantify the dynamics of known and novel
regulators in the context of differentiation, state-of-the-art imaging techniques will be employed to track changes
in protein accumulation over time at a cellular resolution in living roots (Aim 3). Together, these aims should
expand the architecture of the endodermal GRN and begin to define how information flows through it to
orchestrate cell differentiation events. The intellectually stimulating and collaborative environment of Duke
University, coupled with individualized mentoring and enabling technology in the sponsoring lab, provide a
resource-rich environment in which to conduct the proposed experiments. This research plan will facilitate
advanced training in genetics, systems-level transcriptional regulation, multi-dimensional data analysis, and
time-lapse microscopy, thereby providing the foundation for a long-term research program to dissect and model
the GRNs underlying fundamental developmental processes. Insights gained from this work will deepen our
mechanistic u...

## Key facts

- **NIH application ID:** 9908461
- **Project number:** 1F32GM136030-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Rachel Maczis Shahan
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908461

## Citation

> US National Institutes of Health, RePORTER application 9908461, Architecture and Dynamics of a Gene Regulatory Network Controlling Cell Fate (1F32GM136030-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908461. Licensed CC0.

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