The generation of transcriptional differences between cells is the basis of most differentiation and disease. However, our standard measures of RNA synthesis do not register the origins of these differences.
Although useful for a rough sorting of genes to context, widespread techniques such as RT-PCR and RNAseq measure bulk RNA levels from homogenous population extracts. These approaches lose dynamic information from individual cells, and give the impression transcription is a continuous smooth process.
The reality is that transcription is irregular, with strong variable duration periods of activity, interspersed by variable duration “bursts”, or “pulses”, of inactivity. Averaged over millions of cells, this appears continuous. But at the individual cell level, there is tremendous variability, and for most genes, very little activity at any one time. Bursts came to light with the advent of technologies for detecting RNA in single cells, allowing precise measurements of RNA number, or the dynamics of RNA emergence at a gene (see movie below).
We would like to understand the mechanistic basis of pulsing, and how the process is aligned to the regulatory needs of the cell. We are testing the implications of noisy transcription on the generation of diversity between cells during development and for improving regenerative medicine.