High-resolution Studies of Phage-Bacterium Systems
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abstract
This project has three main research directions.Research Direction 1): Cellular decision-making is a ubiquitous key biological process underlyingbiological systems. Stochastic noise is among the most important players in decision-making and poses amajor obstacle to accurate cell-fate prediction. A quantitative understanding of cellular decision-making is vitalfor studying a wide variety of biological phenomena from organism adaptive strategy to metabolism,development, diseases and aging, and consequently for predicting, preventing and treating human diseasessuch as cancer and HIV. We have chosen as our model system one of the simplest biological systems,bacterium E. coli and its virus, phage lambda, a paradigm for understanding cellular decision-makingmechanism. Despite some quantitative understandings of this system as witnessed by our recent paradigm-shift findings, we are still far from predicting cell-fate with single-cell accuracy (modulo irreducible noise). Ouroverarching goal is to formulate a quantitative and comprehensive description of bacteriophage lysis-lysogenydecision-making with single-cell accuracy. The knowledge gained from these "simple" systems will haveenormous boost on understanding decision-making mechanisms in higher organisms where spatial structureplays presumably more significant roles.Research Direction 2): The single-stranded RNA bacteriophages were much less explored due to thelimitation of technology and their small sizes. However, RNA phages are very useful and significant areaswhich will be very impactful for preventing diseases and other diagnostic areas. With the advance of currentfluorescence microscopy, we propose to study the details of RNA phage entry into the cell host. The primarygoal of this project is to determine the mechanisms involved in host recognition and gRNA entry for two ssRNAphages, MS2 and AP205, which infect E. coli through the F-pilus and Acinetobacter spp. through the Type IVmotility pilus, respectively.Research Direction 3): The prospect of CRISPR systems to precisely cleave DNA has led to itstechnology rapidly becoming a premier biotechnological tool for genome editing in animals, plants andmicrobial systems..........
