Mechanism, regulation and impact of transposon activation

/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. Project Number: 1R35GM161651-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Zhao Zhang | Institution: DUKE UNIVERSITY, DURHAM, NC | Award Amount: $523,255 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 MGG-D (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11259978