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LMCB - Laboratory for Molecular Cell Biology

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Jonathan Chubb's picture
LMCB Group Leader, UCL Professor of Quantitative Cell Biology
 

j.chubb@ucl.ac.uk

+44 (0)20 7679 7271
LMCB Room 3.11

 

 

Cellular decision-making

Research synopsis

The primary interest of our laboratory is to understand how cells make decisions about their identity during development. Despite the intense activity in the field of developmental biology for many decades, our understanding of how cells make decisions is decidedly limited. Models tend to fall into two categories— instructive or permissive. Instructive models emphasise the external or inherited trigger, giving the cell no choice. Permissive models view the cell as waiting for some event that triggers a decision already made, often incorporating a central “noise plus feedback” element. These models can be useful in the limited number of apparently simple contexts in which cell fates appear to be determined by a limited number of components, yet in most systems, which are neither wholly instructive nor permissive, and often depend on a highly complex set of interactions between the cell and its environment, these opposing models lack utility.

To allow a deeper understanding of cell decision making, and the generation of more useful conceptual frameworks, we have developed and implemented a range of technologies- with the view that to understand the decision of cell requires monitoring a broad range of regulatory features of single cells, as they differentiate. These approaches encompass both imaging and transcriptomic methods for monitoring the signalling (see Movie 1 below) and gene expression dynamics of single cells. In particular, we use imaging to directly observe the bursts of activity of individual genes in living cells (see Movie 2 below). This approach provides a real time readout of the gene expression decisions of the cell, in parallel with other features of the cells and their environment. We combine these techniques with detailed quantitative analysis of the data, and use modelling and molecular genetics to refine our hypotheses.

Legend for movies | Left: dynamics of long-range signalling in cell populations. Movie shows periodic cAMP signalling waves spreading through populations of Dictyostelium cells. Right: Fluctuations in the transcriptional activity of a single gene in living cells. Newly synthesised RNA, from a gene encoding actin, is visualised as a fluorescent spot using the MS2 labelling technique. Movies such as this reveal the “bursts” or “pulses” of gene firing.

Selected publications

Ford HZ, et al. (2023). Controlling periodic long-range signalling to drive a morphogenetic transition. Elife. 2023 Mar 1;12:e83796. doi: 10.7554/eLife.83796.
Chubb JR, et al (2021). Distributed and centralized control during differentiation. Dev Cell. 2021 56(15):2142-2144. doi: 10.1016/j.devcel.2021.07.007.
Nichols JM, et al (2020). Cell and molecular transitions during efficient dedifferentiation. Elife. 9: e55435. doi: 10.7554/eLife.55435. 
Tunnacliffe E & Chubb JR (2020). What Is a Transcriptional Burst? TIG. 36:288-297. doi: 10.1016/j.tig.2020.01.003.
Deathridge J, et al (2019). Live imaging of ERK signaling dynamics in differentiating mouse embryonic stem cells. Development. doi: 10.1242/dev.172940. 
Antolović V, et al (2019).  Transition state dynamics during a stochastic fate choice. Development. doi: 10.1242/dev.173740.
Tunnacliffe E, et al (2018). Promoter-mediated diversification of transcriptional bursting dynamics following gene duplication. Proc Natl Acad Sci U S A. 115:8364-8369.
 

About the lab

Funders

Funded by Wellcome

Research themes

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

Technology

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

People

Hugh Ford (Postdoc)
Ian Jones (Postdoc)
Vlatka Antolovic (Postdoc)
Elizabeth Westbrook (PhD student)
Paco Chow (Research assistant)
 
Contact JC if you would like to join the lab
 

Collaborators

Adolfo Saiardi (LMCB, UK)
Manju Kurian (ICH, UCL, UK)
Philip Pearce (Mathematics, UCL, UK)
Maddy Parsons (KCL, UK)
Angelika Manhart (University of Vienna, Austria)