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LMCB - MRC Laboratory for Molecular Cell Biology

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Jonathan Chubb's picture

LMCB Group Leader, Professor of Quantitative Cell Biology, Wellcome Trust Senior Research Fellow

j.chubb@ucl.ac.uk

+44 (0)20 7679 7271
LMCB Room 3.11

Twitter @Chubblab

 

Gene Expression Dynamics

Research Synopsis

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.

Selected Publications

Chubb JR (2017). Symmetry breaking in development and stochastic gene expression. Wiley Interdiscip Rev Dev Biol. 6. doi: 10.1002/wdev.284.
Antolović V, et al (2017). Generation of single cell transcript variability by repression. Curr Biol. 27:1811-1817.e3. doi: 10.1016/j.cub.2017.05.028.
Corrigan AM, et al (2016). A continuum model of transcriptional bursting. ELIFE, 5, ARTN e13051. doi:10.7554/eLife.13051
Corrigan AM & Chubb JR (2014). Regulation of transcriptional bursting by a naturally oscillating signal. Curr Biol, 24 (2), 205-211. doi:10.1016/j.cub.2013.12.011
Cannon D, et al (2015). Multiple cell and population-level interactions with mouse embryonic stem cell heterogeneity. DEVELOPMENT, 142 (16), 2840-+. doi:10.1242/dev.120741
Muramoto T, et al (2012). Live imaging of nascent RNA dynamics reveals distinct types of transcriptional pulse regulation. PNAS, 109 (19), 7350-7355. doi:10.1073/pnas.1117603109
Chubb JR, et al (2006). Transcriptional pulsing of a developmental gene. Curr Biol, 16 (10), 1018-1025. doi:10.1016/j.cub.2006.03.092

Funders

Wellcome Trust
BBSRC

Research Themes

Regulation of gene expression, Cellular decision-making, Cell-cell interactions, Development, Dedifferentiation

Technology

Fluorescence microscopy, Live cell imaging, Transcriptomics, Quantitative image analysis, Software development, Mathematical modelling and simulation

People

John Nichols (Postdoc)
Vlatka Antolovic (Postdoc)
Tchern Lenn (Postdoc)
Julia Deathridge (PhD Student, BBSRC Systems Biology)
 

Collaborators

Adolfo Saiardi (LMCB, UK)
Manju Kurian (UCL, UK)