Exploring the CRISPR-based immune system of archaea and bacteria
The goal of my research is to understand the immune system recently discovered in bacteria and archaea, and exploring new applications of the system. I perform my research at the department of Cell and Molecular Biology at Uppsala University, Sweden.
The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a cassette found in one or more copies of the genome of many bacteria and archaea. The cassette consists of short fragments (“spacers”) of e.g. virus DNA separated by repeated sequences. Adjacent to the CRISPR cassette are the Cas (CRISPR-associated) genes, that play an important role in the immune system. The CRISPR system enables the cell to develop resistance to viruses it has been exposed to, by incorporating new virus fragments into the repeat cassette. The system constitute a until now unexpected level of sophistication to bacteria’s and archaea’s defense against viruses, which previously were thought to be limited to innate systems, such as restriction modification systems and abortive infection programs.
The CRISPR system comes in many variants and is highly mobile. Distantly related species can have the same system, while close relatives might have different ones. The same cell can also host several different CRISPR-systems. The common pathway for destroying en infecting phage begins with the transcription of the CRISPR cassette, which is then bound and processed by proteins encoded by the Cas genes. In E. coli the proteins form a complex, Cascade, and each complex retains one CRISPR RNA (crRNA) fragment containing one spacer and flanking repeat sequences. The crRNA then guides the Cascade complex to the virus DNA complementary to the spacer, and inactivates it.
For a popular science article (in swedish) by me about the CRISPR system and its many applications in medicine and biotechnology, please go to the webpage of the journal Forskning och Framsteg.