“There were numerous problems along the way; we found ways to get around them. It took us four years, but the effort paid off..”

Our experiment was one of the first to measure the dynamics of gene expression in live cells with single molecule resolution. It showed that protein expression occurs in random bursts and that the statistics of these bursts can be linked to the molecular mechanisms of transcription and translation. It is an interdisciplinary research combining single molecule microscopy and systems biology.

It describes a new single cell version of an old assay with the ultimate sensitivity of detecting single molecules. By looking at single cells, we were able to see fluctuations that would otherwise be averaged out in a population of cells. These fluctuations then tell us something fundamental about the biochemistry of the cell. So I guess it touches on a little bit of each.

In a way, we were able to make movies of cells "giving birth" to new proteins. It is kind of cool because we typically think of cells following certain programs and producing proteins at the right time. What we see is that what goes on in the cell seems to be pretty random, so the cell might even look a little absent-minded.

This work was derived from our group’s work on probing enzymatic activity of single beta-glactosidase molecules in vitro. We got interested in developing techniques to study gene expression with single molecule sensitivity in live cells. There were numerous problems along the way; we found ways to get around them. It took us four years, but the effort paid off.

I think there are a lot of exciting opportunities in looking at molecular processes in a live cell, which have been called the "test tubes of the 21st century." We are developing imaging techniques to observe these reactions in live cells in real time, as they occur.