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Time-lapse movies provide powerful insights into the behavior of genetic circuits in individual cells.  Here are some examples:

yr_chrom yc_chrom
Gene expression is inherently variable, or "noisy," due to random fluctuations in individual cells. Interestingly, noise can provide insights into the regulatory connections that are active in genetic circuits, helping to answer the question, "Which genes effectively regulate each other?" in any particular cellular context. Here, time-lapse movies of noisy gene expression are shown in a synthetic genetic circuit where a repressor-YFP fusion (green) regulates expression of RFP (red), and CFP (blue) is expressed at an approximately constant level. Cells are imaged in three colors; each movie shows two colors at a time for clarity. Note the strong anticorrelation between RFP and YFP, which is due to repression, and the reduced correlation between CFP and YFP. Scale bar, 5 um.

Burst
Cells use dynamic changes in protein localization to coordinate the expression of their genes. Some transcription factors (proteins that control the expression of genes) collectively burst into the nucleus, remain there for about a minute or two, and then dash back to the cytoplasm. These events occur sporadically, but their frequency (how many times these bursts occur per hour) depends on the environment the cell is in. As a result, hundreds of target genes can be regulated in a coordinated manner: all expressed in proportion to the frequency of bursts, independent of their own detailed chracteristics. Here, upon addition of 150mM Calcium, the transcription factor Crz1, fused to a green fluorescent protein, translocates into the nucleus in coherent bursts of localization that appear as bright spots in individual cells, which otherwise appear as dimmer gray fluorescence. These bursts persist throughout the course of the movie (4 hours) in an unsynchronized fashion across a field of cells. Images were acquired every 15 seconds for 4 hours at room temperature.

differentiation
Bacteria are gamblers. Individual cells of the soil bacteria Bacillus subtilis occasionally differentiate into a "competent" state where they can take up DNA from other cells. How do they know when to become competent, and how long to stay competent? Here, cells express a green fluorescent protein when growing normally, but turn on a red fluorescent protein when differentiating. Note the probabilistic and transient nature of these differentiation events: One cell suddenly decides to become competent (turns red), but then switches back after some time.  Also note another interesting behavior of these cells: Some give up on growth entirely, and differentiate into resilient spores (white objects), which can withstand high temperatures and other environmental challenges. These spores can return to growth by germination when conditions improve. Thus, this movie shows how a clonal (genetically identical) cell population is capable of generating diverse behavior even in relatively homogeneous conditions.

differentiation
The Repressilator is a synthetic genetic circuit that causes individual cells to oscillate in their expression of a fluorescent protein gene. The circuit consists of a 'rock-scissors-paper' negative feedback loop composed of three repressor genes. In this movie, individual cells of a growing E. coli microcolony "twinkle" on and off due to the action of the Repressilator.

Elowitz MB, Leibler S. A Synthetic Oscillatory Network of Transcriptional Regulators, Nature, 2000. (pdf)


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