Mechanism, regulation and impact of transposon activation

The National Institute of General Medical Sciences awarded Duke University $523,255 on March 12, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to support research on the mechanisms, regulation, and impact of transposon activation through the Project Grant mechanism (R35GM161651).

The award funds fundamental research investigating how transposons—elements comprising nearly 50% of the human genome—are regulated and how they contribute to genome stability and disease. The research leverages single-cell resolution reporters and genome-wide approaches in Drosophila to identify regulatory factors controlling retrotransposon activation and silencing, with particular focus on how host factors influence transposon mobilization and how programmed retrotransposon activation may confer adaptive advantages such as enhanced immune responses. The work integrates genomic, genetic, and proteomic methods to examine transposon-host dynamics and their evolutionary significance.

Performance occurs in Durham, North Carolina, with a period of performance extending through February 28, 2031. Duke University's Office of Research Administration administered the award.

Abstract

Transposons, comprising nearly 50% of the human genome, are powerful agents of genomic instability and evolutionary change. Despite their prevalence, the mechanisms regulating transposon activation, their interactions with host systems, and their contributions to health and disease remain largely underexplored. Our research leverages innovative tools, including single-cell resolution reporters and genome-wide approaches, to uncover the mechanisms of transposon regulation and their impacts on host biology. By using drosophila as a powerful genetic system, our previous work has revealed how transposons hijack host DNA repair machinery for replication and how programmed retrotransposon activation shapes host immunity during development. We have also identified novel silencing factors that protect germline and somatic tissues from retrotransposon mobilization, demonstrating the pivotal role of transposon control in genome stability. These findings have laid the groundwork for uncovering host-transposon dynamics and their evolutionary significance. Our future research will expand on these discoveries by exploring the mechanisms underlying transposon regulation, particularly how host factors influence retrotransposon activation and silencing. We aim to identify new regulatory factors through genome-wide screens and dissect their roles in maintaining genome integrity and preventing mobilization. Additionally, we will investigate how programmed activation of retrotransposons can confer adaptive advantages, such as enhancing immune responses or shaping host genome variation. By integrating cutting- edge genomic, genetic, and proteomic approaches, we aim to uncover fundamental insights into transposon biology and its implications for health and disease.