Ryan Tran Rose Hills
Investigating Cellular Conditions that Promote CRISPR-Cas Acquisition
Just over a decade ago, research in a revolutionary genetic engineering tool known as CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats) was pioneered here at UC Berkeley by the Doudna Lab. While the use of CRISPR in disease treatments has been well documented, much of the biology behind the diverse functions of CRISPR in their original hosts, bacteria and archaea, remain unknown. CRISPR-Cas (CRISPR-associated) systems are a type of bacterial immune system that can recognize and inactivate foreign genetic invaders. One fundamental question is how these CRISPR systems remember foreign genetic invaders. During the stage of CRISPR-Cas mediated immunity known as adaptation, CRISPR-Cas proteins integrate sequences from foreign genetic elements into the bacterial genome, thereby allowing the cell to recognize and destroy the source of that foreign DNA in the future. However, how CRISPR-Cas proteins choose these sequences, how these substrates for integration are generated, and the cellular conditions that promote adaptation, remain undefined. As such, we are investigating cellular conditions and host factors that contribute to CRISPR-Cas adaptation, with the hope of later elucidating the mechanism of spacer acquisition. Ultimately, this research has the potential to be developed as an important genetic tool, in that CRISPR-Cas proteins involved in adaptation can be used to store meaningful nucleic acid sequences within the genome to create cellular histories for later gene editing or disease fighting purposes.