Systems biology of bacterial small RNAs

Small RNAs (sRNAs) are post-transcriptional regulators of gene expression that play fundamental roles in the response of bacterial cells to environmental cues. We study the response of genetic networks and architectural motifs that include sRNAs, as well as the cell-to-cell variability in the expression of genes controlled by sRNAs. To do so, we use fluorescence microscopy and microfluidic techniques that allow us to measure directly the concentrations of fluorescently-tagged target proteins in individual cells as they respond to controlled stimuli, as well as single-molecule fluorescence in-situ hybridization to monitor the response at the target transcript level.


development in cyanobacteria

Development in a one-dimensional organism

Life at the level of single cells is subject to unavoidable fluctuations in gene expression, and cells having the same genome may behave rather differently. How can development of a multicellular organism with a precise blueprint take place and cell fates determined in face of the noisy behavior at the level of single cells? We study Anabaena, a cyanobacterial model system comprised of cells arranged in a one-dimensional filament, which forms a nearly-regular developmental pattern of two types of cells in nitrogen-poor environments, with a clear division of labor: one type carries out photosynthesis while the other carries out nitrogen fixation. We interrogate each cell in the organism at all stages of development to study cellular decisions and understand how patterns are formed and maintained.


Target location during horizontal gene transfer

Genomes of living organisms are comprised of very long DNA molecules. A fundamental question is by what mechanisms are specific loci along these genomes found, with high efficiency and at relevant physiological times. We address this question in the case of horizontal gene transfer processes such as viral transduction and conjugation, which result in the rapid acquisition of new traits in bacteria. We use the infection of E. coli cells by bacteriophage lambda, whose DNA integrates at a unique site into the bacterial genome, when following the lysogenic pathway.  To shed light on the mechanisms by which lambda DNA finds its unique integration site, we follow in real time individual lambda DNAs and their integration site within live cells using fluorescent markers, until lysogeny is established, revealing the dynamics of the search process.