The LINE-1 (L1) retrotransposon is a mobile genetic element that constitutes an estimated 17% of the human genome–significantly greater than the portion of the genome that is composed of protein coding genes. While the majority of L1s are inactive due to truncations or other mutations, a few retain their ability to propagate and insert into new regions of the genome via a “copy-and-paste” mechanism. This occurs through the activity of just two proteins, ORF1 and ORF2. ORF1 is an RNA-binding protein encoded by the L1 element that plays an essential but unknown role in L1 retrotransposition. This project will use cryo-electron microscopy and nucleic acid binding assays to characterize the function of ORF1. We will further investigate the interaction of ORF1 with Alu elements, a related transposable element that mobilizes by parasitizing L1 proteins. This work may inform preventative treatments for diseases linked to L1 retrotransposition.

Having worked on this project throughout my time at MIT, I am excited by the opportunity to cumulate and present my research through the SuperUROP program. I’m interested in structural biology because of its ability to inform mechanistic details of biological processes, and I hope to using these tools to investigate transposon-driven diseases. I look forward to having the time and flexibility to dive deeper into my research this semester.