Thawani Lab
Understanding how mobile genetic elements spread
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Human LINE-1 retrotransposon​
Nearly half of the genomic content of mammals are mobile genetic elements. The human genome is also dominated by one mobile element, LINE-1 from the retrotransposon family, which copy-and-paste in the genome using an RNA intermediate.
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​​We employ biochemical, structural biology and genetic approaches to unravel how transposon-encoded proteins and nucleic acids enable their spread. Our recent work reveals how the enzyme encoded by LINE-1 ORF2 initiates retrotransposon insertion near Okazaki fragments of DNA replication forks, suggesting how these repeat elements contribute to a major chunk of the human genome.
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We are interested in unraveling the lifecycle of LINE-1 retrotransposon insertion in the human genome.
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Site-specific R2 retrotransposons​
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R2 retrotransposons are site-specific retrotransposons that insert into the ribosomal DNA loci of many eukaryotes. R2 elements from vertebrates are being engineered into safe-harbor genome insertion tools. In our recent work, we have been employed structural biology approaches to unravel how vertebrate R2 retrotransposons insert genes by resolving distinct mechanistic steps during insertion. By combining these approaches with transgene insertion assays in vitro and in cells, we are elucidating the key features that R2 retrotransposon proteins utilize for precise genome insertion in human cells.
Harnessing retrotransposons for biotechnology
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Understanding the molecular mechanisms that transposons use to mobilize will guide efforts to engineer them for new biotechnological applications.
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We are interested in engineering retrotransposons for programmable genome insertion in human cells for gene therapy and future genome engineering efforts.
