skip to primary navigationskip to content

Random gene pulsing generates patterns during development of living systems

last modified Feb 19, 2020 12:11 PM
A team of Cambridge scientists working at the intersection between biology and computation has found that random gene activity helps patterns form during development of a model multicellular system.

We all start life as a single cell, which multiplies to produce specialised cells that carry out different functions. This complex process relies on precise controls along the way, but these new findings suggest that random processes can also play an important role during the development of living systems.

In research published today in Nature Communications, the scientists from James Locke’s team at Sainsbury Laboratory Cambridge University and collaborators from Andrew Phillip's team at Microsoft Research describe their surprising discovery of order in randomness while studying bacterial biofilms.

A biofilm develops when free-living single-celled bacteria attach to a surface and aggregate to start multiplying and spreading across the surface. These multiplying individual cells mature to form a three-dimensional structure that acts like a multicellular organism.

And while individual cells can survive on their own, these bacteria prefer to work together with biofilms being the dominant form found in nature. This biofilm consortium provides bacteria with important survival advantages such as increased resistance to environmental stresses, including antibiotics.

The researchers developed a new time-lapse microscopy technique to track how genetically identical single cells behave as the living biofilm developed. Dr Eugene Nadezhdin, joint lead-author, said: “We looked at how cells decide to take on particular roles in the biofilm. We found that towards the surface of the biofilm there were two different cell types frequently present – cells that form dormant spores and those that keep growing and activate protective stress responses. Although these two cell types are mutually exclusive, they both could exist in the same location.”

Photos of the live biofilm taken at 12-hour intervals shows the development of the noisy gradient pattern in sigmaB expression over 24 hours.

They focussed on obtaining a detailed picture of how gene expression (whether genes are active or inactive) changes over time for the individual cell types, specifically on expression of a regulatory factor, called sigmaB, which promotes stress responses and inhibits spore formation. They found that sigmaB randomly pulses on and off in cells at hourly intervals, generating a visible pattern of sporulating and stress-protected cells across the biofilm.

Time-lapse tracking cells over 50 hours show sustained random SigmaB pulsing at the top of the biofilm.
Time-lapse tracking cells over 50 hours show sustained random SigmaB pulsing at the top of the biofilm.

To understand the implications of the pulsing, the researchers generated a mathematical model of the sigmaB-controlled stress response and sporulation systems. Dr Niall Murphy, joint lead-author, said: “The modelling revealed that random pulsing enables, at any one time, only a fraction of cells to have high sigmaB activity and activation of the stress pathway, allowing the remainder of cells to choose to develop spores. While the pulsing is random, we were able to show through a simple mathematical model that increasing expression of the gene creates shifting patterns among the different regions of the biofilm.”

The results demonstrate how random pulsing of gene expression can play a key role in establishing spatial structures during biofilm development.

Dr Locke said: “This randomness appears to control the distribution of cell states within a population – in this case a biofilm. The insights gained from this work could be used to help engineer synthetic gene circuits for generating patterns in multi-cellular systems. Rather than the circuits needing a mechanism to control the fate of every cell individually, noise could be used to randomly distribute alternative tasks between neighbouring cells.”

According to Dr Phillips: "This use of noise as an allocation mechanism could have important implications for understanding how living cells share scarce resources, and could potentially be harnessed to develop more efficient genetic systems in the future, for a range of applications in biomanufacturing and therapeutics".


Eugene Nadezhdin, Niall Murphy, Neil Dalchau, Andrew Phillips and James Locke (2020) Stochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms. Nature Communications. DOI: 10.1038/s41467-020-14431-9.

Time-lapse over 60 hours showing the growing biofilm and the pattern development (top of biofilm is on left).
Time-lapse over 60 hours showing the growing biofilm and the pattern development (top of biofilm is on left).



SLCU Reopening Site

(for staff & students)


University of Cambridge Guidance 


We would like to thank NHS staff, key workers and volunteers who are working tirelessly throughout the ongoing coronavirus pandemic in the UK. Our thoughts are with those whose health is impacted here in the UK and around the world.



Supported by the Gatsby Charitable Foundation

RSS Feed Latest news

New insights could help plants fortify walls against root pathogens

Sep 03, 2020

Sainsbury Laboratory Cambridge University (SLCU) researchers, as part of a multidisciplinary international team, have uncovered a mechanism controlling subtle changes to the architecture of cell walls in plant roots that bolsters their defence against Phytophthora palmivora without negatively affecting plant growth.

Giles Oldroyd elected as member of EMBO

Jul 10, 2020

Professor Giles Oldroyd is among 63 other scientists from around the world elected this year as Members and Associate Members of the European Molecular Biology Organisation (EMBO).

Cells in tight spaces – how the cytoskeleton responds to different cell geometries

Jul 09, 2020

Inside every living cell, there is a network of protein filaments providing an interior scaffold controlling the cell’s shape called the cytoskeleton. Research from the Sainsbury Laboratory Cambridge University (SLCU) suggests that this relationship might actually be two-way, with cell geometry itself having the capacity to influence the organisation of the cytoskeleton in living plant cells.

View all news