# Discover the Boosters of Myoblast Fusion

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2023 · $199,320

## Abstract

Project Summary/Abstract
Myoblast fusion unites the strength from otherwise mononucleate cellular compartments, thus
representing a milestone of muscle evolution. Despite the clear significance, the genetic
mechanism that drives the emergence of myoblast fusion has remained largely unknown. The
central goal of this proposal is to understand the biochemical and genetic mechanisms of
myoblast fusion. We recently uncovered the key roles and regulations of two muscle-specific
membrane-coalescing agents Myomaker and Myomixer in human myoblasts. Our
complementation tests suggested that although this duo is sufficient to induce cell fusion, it only
occurs at low efficiency. As such, at least a third factor is required to constitute the highly efficient
fusion system that is normally observed during human development. Our preliminary studies have
delineated the expected roles of these mysterious factors that can be summarized as 1) like
Myomixer, the unknown factor(s) should be able to induce cell fusion together with Myomaker; 2)
When expressed together with Myomixer and Myomaker, the unknown factor(s) should induce
more efficient fusion than by any two-factor combinations; 3) like Myomixer and Myomaker, the
expression of the unknown factor(s) should also be controlled by MyoD the master regulator of
myogenesis. These features provided a clear roadmap to streamline our experiment design that
will ultimately identify such factors that we named Boosters. We propose to first unbiasedly
identify the interactors of Myomixer and Myomaker given their close functional relationships with
the Boosters. In parallel, we will also perform a genome-wide CRISPR knockout screen in unique
models of human myoblasts to systematically identify the Booster genes. The fusogenic activity
of the Booster candidates will be examined through complementary gain/loss-of-function tests in
various cell types. Therefore, our study will integrate the strengths from a broad range of
approaches including gene discovery, comparative proteomics, and gene function study. Our plan
to systematically identify the unknown myoblast fusion factors exactly from human myoblasts also
represents an innovation considering that previous studies have primarily focused on the mouse
and invertebrate models. Ultimately, knowledge gained from this study will provide new insights
into the mechanisms of intercellular fusion in general and may provide new strategies for
improving human muscle development and growth.

## Key facts

- **NIH application ID:** 10705662
- **Project number:** 5R21AR080330-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Pengpeng Bi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $199,320
- **Award type:** 5
- **Project period:** 2022-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10705662

## Citation

> US National Institutes of Health, RePORTER application 10705662, Discover the Boosters of Myoblast Fusion (5R21AR080330-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10705662. Licensed CC0.

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