, assistant professor of molecular biology and genetics in the 麻豆视频 and 麻豆视频, has been named to the Pew Scholars Program to pursue research into advancing gene editing capability.
Kellogg鈥檚 project seeks to harness the power of transposases 鈥 enzymes that catalyze the movement of specific DNA elements 鈥 to engineer novel genome-editing tools. One of 22 early-career researchers selected for the , Kellogg will receive funding for the next four years to investigate what the Pew Foundation calls a 鈥渢imely question鈥 related to human health and disease.
In recent years, scientists have started a revolution in gene editing technology using CRISPR-Cas, a series of genes found naturally in bacteria that encode protein that make precise cuts in the genome, Kellogg said. The discovery won the 2020 Nobel Prize in chemistry.
There鈥檚 a limit, however, to what CRIPSR can do, she said; the molecule makes precise cuts, but is not good at pasting in new genetic material.
鈥淲ith CRISPR-Cas9, introducing a new gene sequence is not that easy,鈥 Kellogg said. 鈥淚t makes the cut, but introducing a new sequence can be tricky.鈥
Kellogg plans to build upon CRISPR technology using her existing expertise in transposons. An entirely different class of macromolecule than CRISPR and found in all cells, transposons naturally cut and paste DNA 鈥 that鈥檚 their function in a cell.
鈥淭hey would be great at delivering new DNA sequences,鈥 Kellogg said. 鈥淏eing able to insert any piece of DNA you want, anywhere in the genome is potentially massive. CRISPR can be metaphorically thought of as scissors, but we don't have a glue stick yet. We don't have any way to paste things together. But with [transposons,] we would have our scissors, we'd have our glue stick and we would be able to start making new things.鈥
Transposon mechanics are complicated, however. Up until recently, Kellogg said, 鈥渋t was generally believed that you couldn鈥檛 control where transposons insert themselves; they could insert anywhere.鈥
Kellogg will collaborate on this project , professor in the Department of Microbiology in the College of Agriculture and Life 麻豆视频, and , professor in the Department of Molecular Biology and Genetics in A&S. The three-lab collaboration is well-positioned to study transposons toward the next step in gene editing, Kellogg said. Kellogg uses cryo-electron microscopy (cryo-EM) and computational protein modeling to . Ke is a CRISPR expert who trained with Jennifer Doudna, co-winner of the 2020 Nobel Prize in Chemistry for work on CRISPR. And Peters focuses on DNA replication, recombination and repair.
Peters, who studies transposons as part of his DNA research, that is a . It was subsequently shown by other researchers that these systems could be reprogrammed in bacteria to integrate a DNA sequence at a desired location in the genome.
鈥淭hat showed that you could control where it was inserting,鈥 Kellogg said. 鈥淭hat was a huge revelation, that these CRISPR-associated transposons can be repurposed for targeted DNA delivery. We can actually use this not just to cut things, but also to paste in the desired DNA sequence. It鈥檚 going to be revolutionary when we can do this reliably and robustly.鈥
To that end, members of the Kellogg lab are combining their expertise in cryo-EM, protein modeling and computational protein design to generate new genome-editing tools.
鈥淭he aims are synergistic: New mechanical insights will guide design strategies and vice versa,鈥 Kellogg wrote in her Pew project proposal. 鈥淐apabilities along these lines would enable precise introduction of new promoter sequences or in-frame coding protein-coding blocks, which are currently either impossible or cumbersome with available gene-editing tools. One can easily imagine that such capabilities will bring about a second revolution in biomedical science, eclipsing CRISPR.鈥
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