# Multi-scale engineering of developmental stochasticity in stem cell derived cardiomyocyte organoids

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $188,508

## Abstract

PROJECT SUMMARY
Biological stochasticity is intrinsic to the growth and developmental processes of all multi-cellular
organisms. Nature utilizes regulatory networks including feedback loops to tightly regulate the
ratio of stochastic versus deterministic gene expression in order to generate robust and
reproducible functionality under dynamic conditions. Stochasticity can affect cellular fate
decisions from bacterial persistence, HIV latency, cancer metastasis, and cellular reprograming,
suggesting that the active modulation and engineering of stochastic control by changing levels of
noise in gene expression can strongly influence multi-cellular patterning. We have previously
identified a novel class of noise modulating compounds that exogenously control gene expression
fluctuations and enhance control of single-cell fate-determination and decision-making in HIV viral
circuitry (Dar et al., Science 2014). This research aims to establish the fundamentals of
engineering noise in the expression of pluripotent transcription factors during stem cell aggregate
differentiation and differentiation into cardiovascular organoids. In addition to exogenous
treatments, synthetic gene circuits that endogenously tune both the mean abundance and noise
levels of targeted pluripotent factors, such as Nanog, Oct4, and Sox2, will be implemented. A
library of stem cell aggregates will be created with diverse stochastic backgrounds and
differentiated into cardiovascular organoid for further characterization. This research will establish
a foundation towards control of heterogeneous growth and development in other multi-cellular
systems by providing fundamentals for the stochastic engineering and synthesis of complex tissue
patterning. This highly interdisciplinary effort includes scientific areas relevant to the mission of
the NIH such as biological, clinical, physical, chemical, computational, engineering, and
mathematical sciences. The proposed areas of research combine tissue engineering, systems
and synthetic biology, single-cell biophysics, and pharmaceutical sciences. The research will train
and support two faculty members, a postdoc, and a graduate student for the three year term.

## Key facts

- **NIH application ID:** 9968328
- **Project number:** 5R21EB025388-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Roy David Dar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,508
- **Award type:** 5
- **Project period:** 2018-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968328

## Citation

> US National Institutes of Health, RePORTER application 9968328, Multi-scale engineering of developmental stochasticity in stem cell derived cardiomyocyte organoids (5R21EB025388-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9968328. Licensed CC0.

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