# Sizing and Scaling in Functional Muscle Cells

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $463,016

## Abstract

Project Summary/Abstract
 Cell size is one of the most basic and defining features of a cell. However, the mechanisms controlling size
are poorly understood. This is particularly true for muscle cells, which have a remarkable capacity to increase
their size in response to exercise, and to decrease in size upon inactivity, aging, or disease. The long-term
goal of this proposal is to define genes, mechanisms, and networks responsible for muscle size scaling under
normal, hypertrophic, and atrophic conditions. These mechanisms will translate both to a better understanding
of fundamental aspects required to build a functioning muscle and to better strategies for treating muscle
atrophy due to aging and disease. The objective of this proposal is to define salient features of the muscle cell
that determine muscle size using genetic, cell biological, mathematical modeling and imaging approaches. We
will perform these studies in the Drosophila larval musculature, taking advantage of its cellular simplicity, easy
readouts for cell function, optical clarity, and the availability of advanced tools for imaging and tissue-specific
manipulation of genetic, environmental, and mechanical factors in vivo. In Aim 1, we will acquire and
mathematically model measurements of cell and organelle size, particularly of nuclear distribution, size/ploidy,
and activity, to determine those that scale with muscle size under normal, hypertrophic and atrophic conditions.
We will use this model to predict the importance of specific parameters and interrelationships between these
parameters to generate functional muscle sizes. We will test our predictions by genetically manipulating the
specific measured parameters. Already we have found novel compensatory mechanisms that are invoked to
achieve a functioning muscle cell: nuclear area can be adjusted to account for differences in nuclear numbers
in the same sized muscle. In Aim 2, the localized effects of innervation, and the effects of mechanical forces on
individual nuclei size and activity and overall cell size, will be investigated. Mechanisms responsible for altering
nuclear size and activity will be uncovered. Lastly, Aim 3 will focus on the investigation of Myonuclear Domain
sizes in normal, hypertrophic and atrophic muscles. We will also mathematically model and test mechanisms
by which Myonuclear domains are created and maintained under normal, hypertrophic and atrophic conditions.
Altogether, these experimental and computational approaches will identify defining parameters of muscle cell
size under normal, hypertrophic and atrophic conditions, and their physiological range required for muscle
function. These data will reveal general principles of cell size regulation, provide insight to how improper
regulation of these processes results in disease, and inform regenerative medicine aimed at muscle.

## Key facts

- **NIH application ID:** 9984863
- **Project number:** 5R01GM121971-04
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** MARY K BAYLIES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $463,016
- **Award type:** 5
- **Project period:** 2017-09-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984863

## Citation

> US National Institutes of Health, RePORTER application 9984863, Sizing and Scaling in Functional Muscle Cells (5R01GM121971-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9984863. Licensed CC0.

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