# Studying the mammalian regulatory circuits by developing single-cell multi-omics technologies

> **NIH NIH K99** · LUDWIG INSTITUTE  FOR CANCER RES  LTD · 2022 · $66,190

## Abstract

Project Summary/Abstract
How the identical genome sequence produces diverse cell types during development remains a fundamental
question in biology. Recent technology advancements in single-cell genomics provided excellent opportunities
to study the molecular profiles during development and in disease at unprecedented resolution. However,
monitoring individual modalities from single cells at a time runs the risk of obtaining only partial pictures from the
complex regulatory network. Multi-modal single-cell genomics tools would be desired to overcome this limitation.
I recently invented a method for ultra-high-throughput joint analysis of open chromatin and transcriptome from
the same single cells (Paired-seq) and demonstrated its potential for comprehensive investigations of the cell-
type-specific regulatory programs from heterogenous brain tissues. In this K99/R00 application, I propose to
further develop a set of new single-cell multi-omics tools to study the dynamic and cell-type-specific regulatory
circuits during mammalian development. I will improve the sensitivities and coverages of Paired-seq and develop
a computational method for single-cell multi-omics analysis from the phenotypic level (Aim1). Subsequently, I
will further develop a method for high-throughput single-cell joint analysis of histone modifications/transcription
factors binding with gene expression (Paired-tag) for analysis of molecular programs from the mechanistic level
(Aim2). Finally, I will apply these technologies to study the dynamic and cell-type-specific molecular programs in
mammalian developing germ cells, and to identify and validate novel regulators during this process (Aim3).
Overall, the results from this proposal will provide new technologies for the study of epigenetic programs in
complex tissues and during development at single-cell resolution, and providing more complete views of the
gene regulatory circuits during mammalian germ cell development. My career goal is to lead an independent
research group focusing on integrating novel experimental and computational technologies to understand the
underlying principles controlling mammalian development. During the K99 phase, I will continue to receive
experimental and computational training from my postdoctoral mentor Dr. Ren and collaborators/advisory
committee at UC San Diego and the Salk Institute. The rigorous mentored support and results obtained in the
K99 phase will facilitate my transition to an independent investigator in the R00 phase and lay the foundation for
my future career.

## Key facts

- **NIH application ID:** 10312802
- **Project number:** 5K99HG011483-02
- **Recipient organization:** LUDWIG INSTITUTE  FOR CANCER RES  LTD
- **Principal Investigator:** Chenxu Zhu
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $66,190
- **Award type:** 5
- **Project period:** 2020-12-07 → 2022-04-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312802

## Citation

> US National Institutes of Health, RePORTER application 10312802, Studying the mammalian regulatory circuits by developing single-cell multi-omics technologies (5K99HG011483-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10312802. Licensed CC0.

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