Research
Bacteria and phages have been locked in battle for billions of years, spurring bacteria to invent a diverse array of anti-phage defenses, most of which have not been discovered. In response, phages have devised a myriad of counter-defenses to overcome bacterial immunity and re-establish infection. Because most defense and counter-defenses are undescribed, phage infection outcomes are difficult to predict, and their impacts hard to control.
Functional Selections
Functional selections use a survival phenotype to identify genes with desired activities from enormous DNA libraries. Because phage infections are life-or-death scenarios for both the viruses and bacteria involved, functional selections are well suited to find new genes involved in this conflict. This is especially true because many phage and bacterial genes have no recognizable function. There are few alternatives to explore their activities!
Anti-CRISPRs:
Discovery and Function
Anti-CRISPRs are proteins encoded by phages and other mobile genetic elements for overcoming CRISPR-Cas systems in bacteria (and archaea). Because anti-CRISPRs inhibit CRISPR-Cas activity in vitro, in eukaryotic cells, and in bacteria, they can augment emerging technologies for genome editing and microbiome manipulation. However, most anti-CRISPRs in nature have not been discovered – usually because their genes are not recognizable. Functional selections can overcome this obstacle to reveal hidden genes, illuminate obscured mechanisms, and unlock new applications.
New Frontiers
Many systems conspire to determine phage infection outcomes in nature and each is subject to intense and dynamic selective pressures. Most of these evolutionary battlegrounds are poorly defined, representing lifetimes and lifetimes of potential discoveries. We believe that functional selections are a great way to gain toeholds in these new frontiers, and that detailed mechanistic studies are the best approach to coax out their secrets.
Image Credits
Tamanash Bhattacharya
Danica Schmidtke
Tamanash Bhattacharya