Endogenous circadian clocks align cellular physiology with diurnal light/darkness cycles on Earth, endowing organisms from unicellular cyanobacteria to multicellular plants and mammals, with a selective fitness advantage. Using fluorescence microscopy and microfluidic techniques we study at the single cell level circadian clocks and the remarkable reliability they can display in Anabaena, a multicellular cyanobacterium that has a one-dimensional structure. This allows us to probe the effects of cell-cell communication on clock synchrony and coherence, noisy fluctuations in protein copy numbers and phosphorylation states as well as the interplay between clocks and other processes in the cell such as cell division and differentiation. We model these phenomena theoretically using stochastic approaches.
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.
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.