# Post-transcriptional Control of Adaptive Tissue Growth

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $318,910

## Abstract

PROJECT SUMMARY
 Here we seek to understand how translational control of mRNAs within adult stem cells controls their
ability to divide symmetrically. This area of study is significant because such symmetric renewal is a
fundamental but poorly understood behavior of stem cells that is responsible for tissue growth, remodeling
and regeneration in animals including humans. Addressing this deficit, we have found that the RNA-binding
protein LIN-28 is specifically expressed in adult intestinal stem cells (ISCs) of the Drosophila model
organism and is required for the expansion of this stem cell population during growth of the intestinal
epithelium in response to food consumption. Since vertebrate LIN-28 is also known to promote
regeneration, the goal of this grant is to use the unique advantages of the genetically tractable Drosophila
model to rigorously delineate the conserved mechanistic activity, relevant substrates, and required cofactors
that LIN-28 normally uses to promote the symmetric renewal of stem cells. We propose to accomplish this
goal by focusing our experiments on a specific hypothesis that is based on our functional analysis of LIN-28
in ISCs as well as large scale proteomic and transcriptomic analyses we conducted that identified putative
LIN-28 binding partners and mRNA targets in ISCs. Our hypothesis is that a stem cell specific
ribonucleoprotein (RNP) complex, including LIN-28, boosts translation of target mRNAs during nutrient-
deprived conditions in order to poise stem cells to divide symmetrically when nutrients become available. To
accomplish our goal, we propose the following three overlapping areas of investigation: 1) Test whether
adaptive growth is controlled by the ratio between LIN-28 and a second RNA-binding protein called FMR1 in
ISCs; 2) Determine how LIN28 and FMR1 regulate mRNA targets during adaptive tissue resizing; 3)
Investigate whether LIN28 and FMR1 function by excluding one another from a larger mRNP complex. We
expect that these proposed studies will delineate a novel, conserved pathway that controls symmetric self-
renewal of stem cells in response to environmental cues. Medical interventions that trigger this pathway
could be used to promote the regenerative process and therefore would have wide applicability in treating
aging-related and congenital disorders.

## Key facts

- **NIH application ID:** 9984492
- **Project number:** 5R01GM124220-04
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** BRIAN R CALVI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $318,910
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984492

## Citation

> US National Institutes of Health, RePORTER application 9984492, Post-transcriptional Control of Adaptive Tissue Growth (5R01GM124220-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984492. Licensed CC0.

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