We are interested in examining (sub)cellular decision-making processes and cellular dynamics in various systems. Living systems make decisions by integrating information from their environments in order to optimize their own fitness. This decision-making process has many intricacies, with a dual nature characterized by stochasticity and determinism. Our primary goal is to determine how multiple environmental and genetic factors, some deterministic and some stochastic, impact developmental outcomes. The major tools used for our studies are high-resolution and super-resolution fluorescence microscopy combined with mathematical modeling.
Cell-fate decision making
The system of E. coli and its virus, phage lambda, has long served as a paradigm for cell-fate bifurcation. As a temperate phage, upon infecting an E. coli cell,lambda can choose either the lytic (virulent) pathway producing ~100 new progeny particles and lysing the cell, or the lysogenic (dormant) pathway with its DNA integrated into the host chromosome and replicating along with the host. Recent single-cell, single-molecule studies have yielded many interesting findings including individual phage voting, interplay of phage competition and cooperation. We are interested in formulate a quantitative picture of lysis-lysogeny decision making of lambda. We have also expanded our study to another model system, phage P1, well known for its high rate of generalized transduction. P1 has unusual properties of lysis-lysogeny. We aim to elucidate the fundamental mechanisms of these model systems, which will shed important light on phage therapy treating multi-drug resistant bacteria and how other viruses operate in the host including higher organisms.
Trinh, J.T., Shao, Q., Guan J., and Zeng, L., “Emerging Heterogeneous Compartments by Viruses in Single Bacterial Cells”, Nature Communications 11, 3813 (2020)
Q. Shao, J. T. Trinh, L. Zeng, High-resolution studies of lysis-lysogeny decision making in bacteriophage lambda. J. Biol. Chem. 294, 3343–3349 (2019).
Infection cycle of ssRNA phages
ssRNA phages are small viruses which infect bacteria through retractile pili. We are particularly interested in the entry dynamics of genomic RNA from the phage capsid to the cell, virus replication and assembly inside the cell, and the impact on the retractile pili as a result of ssRNA phage infection. We aim to understand these fundamental processes and to engineer these phages as novel antibacterials.
Harb, L., Chamakura, K., Khara, P., Christie, P.J., Young, R., and Zeng, L., “ssRNA Phage Penetration Triggers Detachment of the F-pilus”, PNAS 117(41), 25751-25758 (2020)
To Academic Professional Track Faculty