Thursday March 13th, 1pm
Thursday March 20th, 1pm
1995, BA, Cambridge University
2000, PhD, University College London
Tel: +44 (0)207 679 7271 (Office)/ +44 (0)207 679 7273 (lab)
Imaging transcriptional dynamics
Despite the generation of transcriptional differences between nearby related cells being the basis of most differentiation and disease, our standard measures of RNA synthesis do not register the origins of these differences. Although useful for a preliminary rough sorting of genes to context, the widespread techniques of Northern blotting, microarrays, RT-PCR and RNA-Seq 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 periods of inactivity (see movie sequence). Averaged over millions of cells, this appears continuous. But at the individual cell level, there is considerable variability, and for most genes, very little activity at any one time. Transcription of genes, the process which transforms the stable code written in DNA into the mobile RNA message can occur in "bursts" or"pulses" (see movie sequence). These phenomena have recently come to light with the advent of new technologies, to detect RNA in single cells, allowing precise measurements of RNA number, or RNA emergence at a gene. We would like to understand the mechanistic basis of pulsing, and how it is responsive to signals, developmental and chromatin context. And we are testing the implications of noisy transcription on the generation of diversity between cells in developmental and clinical contexts.
2000-2003: Post-doctoral fellow, MRC Human Genetics Unit, Edinburgh
2000-2005: Post-doctoral fellow, Albert Einstein College of Medicine, New York
2005-2011: Principal Investigator, College of Life Sciences, University of Dundee
2012- present: Group leader, MRC LMCB and Department of Cell and Developmental Biology
1. Muramoto T, Cannon D, Gierlinski M, Corrigan A, Barton GJ, Chubb JR. Live imaging of nascent RNA dynamics reveals distinct types of transcriptional pulse regulation. PNAS (in press).
2. Stevense M, Chubb JR, Muramoto T (2011). Nuclear organisation and transcriptional dynamics in Dictyostelium. Dev Growth Differ 53:576-86.
3. Chubb JR and Liverpool TB (2010). Bursts and pulses: insights from single cell studies into transcriptional mechanisms. Current Opinion in Genetics and Development 20:478-84.
4. Muramoto T, Mueller I, Thomas G, Melvin A, Chubb JR (2010). Methylation of H3K4 is required for inheritance of active transcriptional states. Current Biology 20:397-406.
5. Mueller I, Boyle S, Singer RH, Bickmore WA and Chubb JR (2010). Stable morphology, but dynamic internal reorganisation, of interphase human chromosomes in living cells. PLOS ONE e11560.
6. Stevense M, Muramoto T, Mueller I, Chubb JR (2010). Digital nature of the immediate-early transcriptional response. Development 137:579-84.
7. Chubb JR (2009). Gene activation at the edge of the nucleus. EMBO J 28:2145-2146
8. Muramoto T and Chubb JR (2008) Live imaging of the Dictyostelium cell cycle reveals widespread S phase during development, a G2 bias in spore differentiation and a premitotic checkpoint. Development. 135:1647-57.
9. Chubb JR*, Trcek T, Shenoy SM, Singer RH. (2006).
Transcriptional pulsing of a developmental gene. Curr Biol. 2006 16:1018-25.
The Chubb Lab
As an undergraduate I studied pure physics at The University of Dundee. After investigating the structure and formation of amyloid aggregates associated with Alzheimer’s disease for my PhD at the Cavendish Laboratories in Cambridge, I moved into Jonathan Chubb's group where I am now using a variety of microscopy techniques to study the single cell gene expression dynamics in Dictyostelium and a variety of mammalian cell types.
am interested in studying the heterogeneity of behaviour in cell
populations, principally the stochastic 'bursts' of transcription
observed in many cells, by developing high-throughput image processing
and analysis techniques and computer simulation.
completed my PhD in biophysics with Prof Dame Athene Donald at the
Cavendish Laboratory, using particle tracking microrheology to study
the formation of protein gels. I developed my interest in measuring
biological phenomena using automated image processing in a short
postdoc with Viji Draviam in the Department of Genetics, University of
Cambridge, studying dynamic spindle orientation.
I completed my PhD at the University Paris 7 where I studied cellular adaptation to environmental variations, and more particularly the response of the yeast Saccharomyces cerevisiae to osmotic stresses. By the combination of lab-on-a-chip devices, molecular biology and microscopy tools, I analyzed how time varying hyper-osmotic shocks influence single-cell response kinetics of signal transduction, compartmentalization and intracellular trafficking.
As I am interested in studying single cell behavior, I joined the group of Jonathan Chubb where I study transcriptional dynamics in Dictyostelium by the use of high-resolution live imaging combined with state-of-the-art image analysis.
Page last modified on 22 apr 13 10:06 by Edward D Whitfield