Focus

Structural and biochemical mechanisms of retrotransposition.

Research

Nearly 30% of our genome is made up of two retrotransposable elements: long-interspersed nuclear element-1 (LINE-1) and the Alu element. Although most are inactive, a small subset of LINE-1s and Alus can still mobilize. This means that they can copy themselves from one location in and insert themselves into another. Consequently, LINE-1 and Alu mobility can be a significant mutagen. Their movement can result in numerous genetic diseases, is thought to drive oncogenic rearrangements in some cancers, and is linked to age-associated inflammation. Moreover, there has been a resurgence in the development of mobile genetic elements into tools for biotechnology.

Yet, despite a prevalence in human diseases and potential use as genetic tools, many mechanistic aspects of LINE-1 and Alu retrotransposition are poorly understood. The lab aims to understand how these elements retrotranspose at a molecular level through a combination of biochemical reconstitution, in vivo assays, and cryo-electron microscopy (cryo-EM). Understanding the interactions between the retrotransposition machinery, retrotransposon RNA, and target DNA will be essential for therapeutically inhibiting LINE-1 and Alu activity, which has a high incidence of reactivation in human disease. Moreover, the proposed work will yield the mechanistic insights necessary to engineer LINE-1 and Alu elements as molecular biology tools: i.e., modifying their substrate RNA or target DNA specificity.

Biography

George earned his B.A. in Molecular Biology, Biochemistry, and Math from Rutgers University in 2012. He earned his PhD at UC Berkeley, with Professor Donald Rio, focusing on the structural mechanism of Drosophila P element transposition. In 2020, George joined Dr. Kelly Nguyen at the MRC Laboratory of Molecular Biology in the UK, where he applied cryo-EM to study human telomerase and shelterin complexes. His postdoctoral research provided significant insights into the molecular mechanisms of telomere maintenance, earning him the Jane Coffin Childs Fellowship in 2021 and the MRC-LMB Joan A. Steitz Postdoc Prize in 2022. In January 2025, George will begin his independent career at Princeton University’s Department of Molecular Biology.

Honors & Awards

2022

• MRC-LMB Joan A. Steitz Postdoc Prize

2021

• Jane Coffin Childs Postdoctoral Fellowship