# Dissecting CEBPB Function with Synthetic Biology and Imaging

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $646,793

## Abstract

Project Summary
 Caloric restriction and reduced mTOR signaling mitigate the adverse effects of aging. They do not translate
into effective anti-aging therapies though, because diets are difficult to maintain and mTOR inhibitors exhibit
undesirable side effects. The transcription factor CEBPB drives many of the undesirable effects of aging
downstream of the TOR pathway. The levels of its short isoform called LIP increase with age; loss of LIP
increases lifespan and provides health benefits, while expression of LIP alone increase tumorigenicity.
Reprogramming CEBPB and LIP therefore holds great promise as a tool to control aging.
 Pioneering studies indicated that LIP activates transcription of its target genes, while the canonical long
isoform of CEBPB, LAP, is a transcription repressor. Recent evidence draws a more complex picture:
 - both isoforms are extensively modified by phosphorylation, acetylation (and many others), and those
 modifications impact their activity;
 - dimerization of CEBPB with other factors impacts its function;
 - finally, LIP rescues CEBPB knock-out, suggesting that LIP is not simply a dominant negative inert
isoform.
 Understanding how these regulatory dimensions are integrated by CEBPB isoforms is a pre-requisite to
develop technologies able to reprogram aging.
 Here, we deploy synthetic biology approaches in order to dissect how the CEBPB isoforms, their
dimerization partners and post-translational modifications impact the nuclear dynamics of CEBPB and its
transcription regulation activity.
 We also develop synthetic tools to visualize and perturb the LAP:LIP ratio in individual cells. Being able to
perturb aging regulators in single cells will enable measuring the contributions of cell-autonomous aging
phenotypes and those driven by signals between cells. It will also provide precise tools to dissect one of the
common hallmarks of aging: increased heterogeneity of expression.

## Key facts

- **NIH application ID:** 10345006
- **Project number:** 1R01AG075272-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Timothee Lionnet
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $646,793
- **Award type:** 1
- **Project period:** 2022-02-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10345006

## Citation

> US National Institutes of Health, RePORTER application 10345006, Dissecting CEBPB Function with Synthetic Biology and Imaging (1R01AG075272-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10345006. Licensed CC0.

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