Like any other organism, bacteria are constantly exposed to pathogenic threats, such as viruses and plasmids. The Aviram Lab is interested in understanding how bacterial cells protect themselves from invaders, focusing particularly on the CRISPR-Cas adaptive immune system. CRISPR-Cas systems have a remarkable capability to form immunological memories by integrating short segments of invading genomes, called “spacers” into the CRISPR locus in the genome of the bacterial host. These spacers are later transcribed into crRNA that are loaded on Cas nucleases to target them to cleave and block recurring infections.
Our work focuses on the type III CRISPR-Cas system, one of the most complex and understudied CRISPR-Cas types. We have previously demonstrated that this system is capable of acquiring new spacers by two distinct modes—one arising from transcribed regions and the other from exposed dsDNA ends. This suggests the existence of underlying mechanisms that link the spacer-acquisition machinery to the bacterial transcription apparatus and to processes ensuring DNA integrity. Using genetics, genomics, high-throughput screening and live fluorescence imaging, our research examines how these spacers are acquired, regulated, and maintained, even when they pose a risk of the bacterial host itself. By exploring these molecular dynamics, we hope to expand our understanding of bacterial defense and its impact on bacterial physiology, adaptability, and evolution.
Publications Highlights
Aviram N*^, Shilton AK*, Reis BS, Brivanlou A, Marraffini LA^ (2024). Cas10 relieves host growth arrest to facilitate spacer retention during type III-A CRISPR-Cas immunity. Cell Host & Microbe 32(12), 2050-2062.
Aviram N^, Thornal AN, Zeevi David, Marraffini LA^ (2022). Different modes of spacer acquisition by the Staphylococcus epidermidis type III-A CRISPR-Cas system. Nucleic Acid Research 50, 1661-1672.