# Design principles and dynamic gene control in embryonic development

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2020 · $386,827

## Abstract

Project Summary
Recent advancements in high-throughput sequencing techniques have provided many insights into one of the
most fundamental questions in modern biology: gene regulation. Such “seq” techniques have elucidated
enhancer distributions in the genome, revealed distinct chromosome conformation in a nucleus, and identified
hotspots within the genome that are highly associated with disease phenotypes. And yet, there remain
unanswered questions. For example, while spatial boundary of gene expression pattern has been studied
extensively, the kinetics of gene expression is not as well understood. We know that enhancer and promoter
need to interact with each other to produce mRNA, but it is not clear how often, or how long they need to
interact to initiate transcription. Moreover, while complete removal of an enhancer is known to abolish gene
expression, the effect of moderate disruptions in enhancer or enhancer-promoter interactions on development
is yet to be characterized. I believe that recent advancement in imaging techniques can provide equally
exciting discoveries in gene regulation by complementing the “seq” techniques. In the next five years, I
envision achieving molecular-level understanding of dynamic gene control that ensures normal development,
using combination of live imaging, quantitative image analysis, and mathematical modeling.
Using early Drosophila embryo, I propose to study three aspects of gene control that affect developmental
phenotypes: (1) multiple enhancers contributing to developmental robustness by reducing cell-to-cell variability
in transcription, (2) characteristics of enhancer-promoter interactions that guarantee transcriptional initiation,
and (3) modulations in chromosomal loop domain affecting the error-rate of enhancer-promoter interactions
and leading to variable developmental phenotypes. The proposed study will provide exciting new perspectives
on the field of gene regulation during development. The insights obtained from this interdisciplinary study will
be relevant to all other gene expression phenomena underlying metabolism, disease, and other aspects of
human physiology.

## Key facts

- **NIH application ID:** 9983774
- **Project number:** 5R35GM133425-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Bomyi Lim
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,827
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983774

## Citation

> US National Institutes of Health, RePORTER application 9983774, Design principles and dynamic gene control in embryonic development (5R35GM133425-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983774. Licensed CC0.

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