# Genomic and Physiological Impact of Transposable Elements.

> **NIH NIH R35** · CORNELL UNIVERSITY · 2024 · $542,340

## Abstract

PROJECT SUMMARY
Transposable Elements (TEs) make up a large fraction of vertebrate genomes, including half of the
human genome. The mutagenic properties of TEs are well documented and they are important drivers of
genetic variation between and within species. However, how this enormous source of genetic variation
has shaped the evolution and biology of species remains poorly understood. Our MIRA project is
designed to yield transformative insights into the biological significance of TEs in evolution and disease.
Our previous research has focused on the long-term impact of vertebrate TEs in driving genetic
innovations. Notably, we showed that TEs have been a recurrent source of raw sequence material co-
opted during vertebrate evolution to create new cis-regulatory elements driving changes in gene
expression and new protein-coding genes underlying the emergence of novel cellular functions. Most of
these events involved ancient TEs long inactive transpositionally. In this next funding cycle, we are turning
our attention to young TEs -- those recently or currently mobile. We focus on the developmental impact
of young TEs in humans and in zebrafish, a powerful model organism for studies of vertebrate
development. By focusing on the functional impact of young retroelements in embryonic development we
will uncover the molecular underpinnings of evolutionarily recent biological innovations. Notably, we will
investigate the regulatory contribution of TEs in defining features of the human placenta, such as its deep
invasion into maternal decidual tissue, and the functional significance of endogenous viral-like particles
produced in the early stages of human embryonic development. Our work will also uncover general principles
that lead to the cooption of specific TE sequences for cellular function. Specifically, we will test a new
provocative model of host-TE interaction in which organismal development becomes dependent on TE-
encoded products. We will test this ‘addiction model’ by studying the trans-regulatory activities of Gag (capsid)
proteins encoded by endogenous retroviruses in human and zebrafish for which we have obtained preliminary
evidence they modulate embryonic developmental processes. The outcomes of this project are expected to
shift our view of host-TE interactions from conflicting to mutualistic. Our studies will also yield new mechanistic
insights into poorly understood disease processes, such as pregnancy loss by preeclampsia and
neurodevelopmental disorders, implicating the dysregulation of young TEs.

## Key facts

- **NIH application ID:** 10840322
- **Project number:** 5R35GM122550-07
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Cedric Feschotte
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $542,340
- **Award type:** 5
- **Project period:** 2017-09-08 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840322

## Citation

> US National Institutes of Health, RePORTER application 10840322, Genomic and Physiological Impact of Transposable Elements. (5R35GM122550-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10840322. Licensed CC0.

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