# Single-cell analysis and synthetic control of mammalian chromatin dynamics and gene regulation

> **NIH NIH R35** · STANFORD UNIVERSITY · 2024 · $385,985

## Abstract

PROJECT SUMMARY
Gene and chromatin regulation are at the core of many human biological processes such as development and
aging, and play an important role in disease, including during immune response and cancer progression. Much
work was done over the last few decades to catalogue transcription factors and chromatin regulators, determine
the gene regulatory elements where they act, and measure the chromatin states associated with them across
different cell types.
However, there are over a thousand transcription factors and chromatin regulators controlling gene expression
in human cells. Similarly, on the DNA side, there are tens of thousands of gene regulatory elements in the human
genome. Moreover, the function of these regulatory proteins (and hence of the DNA elements they bind to) can
change over time in response to signals such as cell differentiation or immune responses to viral infections.
These processes also show cell-to-cell heterogeneity that is important in cell-fate decisions. Consequently, our
efforts to understand the general principles of gene and chromatin regulation in human cells and the type of
dynamical responses they enable are severely limited by the fact that most experimental methods can only study
a handful of proteins at a time, generally use methods that average across cell populations, and often only
measure correlations at a given point in time.
In order to address these challenges, we combine high-throughput synthetic biology, single-cell measurements
of gene expression dynamics using fluorescence microscopy and flow cytometry, and mathematical modelling
for both a systematic and in-depth understanding. We use these tools to answer essential question about gene
and chromatin regulation in human cells: (1) How do transcription factors work: what are the biophysical rules
governing their effector domains and interactions with coactivators and corepressors, and what type of dynamic
responses do they enable? (2) How does the dynamics of gene silencing, activation and epigenetic memory
depend on the architecture of gene regulatory elements such as enhancers, promoters, terminators and
insulators? (3) What are strategies that viral proteins have evolved to interface with and perturb gene and
chromatin regulation in human cells in order to increase viral gene expression and disrupt immune responses?
Together, answering these questions quantitatively will help uncover the basic principles of gene regulation in
human cells in the context of a dynamic chromatin environment, will provide new tools for genetic, epigenetic
and cellular therapies, and will inform treatments of viral infections and immune disorders.

## Key facts

- **NIH application ID:** 10765555
- **Project number:** 2R35GM128947-06
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lacramioara Bintu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,985
- **Award type:** 2
- **Project period:** 2018-07-05 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765555

## Citation

> US National Institutes of Health, RePORTER application 10765555, Single-cell analysis and synthetic control of mammalian chromatin dynamics and gene regulation (2R35GM128947-06). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10765555. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*