Periodic Reporting for period 3 - CRISPRsition (Developing CRISPR adaptation platforms for basic and applied research)
Periodo di rendicontazione: 2022-12-01 al 2024-05-31
We partially achieved two aims of the project and significantly advanced the other one. The first aim to develop a robust adaptation system and then use it to identify adaptation inhibitors was partially achieved by developing a system that allowed us to enrich the proteins that manifest the highest recorded adaptation activity. The adaptation system can be beneficial for society as it is a bacterial memorization system. It allows the bacteria to store in their DNA the information of viruses that attacked them. Memory storage in DNA is a feature that may advanced technology immensely. It can decrease the size required for storage dramatically in small devices and allow humanity to develop nano-sized robots and computers. In fact, researchers have already used the adaptation system to code movies and images in the DNA. Our accomplished aim will enable up to 10 fold better efficiency in this process.
We further identified, in an interdisciplinary effort, novel defense systems against bacteriophages, that are located in a specific genetic island in many bacteria. Identifying new defense systems may revolutionize biotechnology in ways that we sometimes cannot even imagine. For example, the antibodies, a defense mechanism against foreign elements, enabled numerous biotechnological developments including even drugs against cancer. Restriction enzymes and the CRISPR-Cas system, that were identified as a defense mechanism against bacterial viruses have revolutionized the way that we carry out molecular biology. They also allow unprecedented precision in DNA cleaving and genome editing and paved the way for developments that significantly improve the well-being of humanity. These findings are now in revision in Nature Microbiology.
These two achievements combine both basic and applicable studies of the adaptation system and of phage-bacteria relations, and significantly contribute to both aspects.
We further identified, in an interdisciplinary effort, novel defense systems against bacteriophages, that are located in a specific genetic island in many bacteria. Identifying new defense systems may revolutionize biotechnology in ways that we sometimes cannot even imagine. For example, the antibodies, a defense mechanism against foreign elements, enabled numerous biotechnological developments including even drugs against cancer. Restriction enzymes and the CRISPR-Cas system, that were identified as a defense mechanism against bacterial viruses have revolutionized the way that we carry out molecular biology. They also allow unprecedented precision in DNA cleaving and genome editing and paved the way for developments that significantly improve the well-being of humanity. These findings are now in revision in Nature Microbiology.
These two achievements combine both basic and applicable studies of the adaptation system and of phage-bacteria relations, and significantly contribute to both aspects.
The main results achieved so far are the identification and characterization of the most robust adaptation proteins, a study accepted to Nucleic Acids Research, and the identification and characterization of novel defense islands, a study in revision in Nature Microbiology. Another study, published in PNAS, shows that the T5-015 combines with a DNA repair protein to cleave DNA. We further developed and published a method for engineering phages, and also identified a new phage protein that inhibits bacterial division. These findings were published in RNA Biology and Microbiology Spectrum, respectively.
The above progress is beyond the state of the art. We anticipate to achieve the other aims as well till the end of the project.