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Dr Bruno Martins

Dr Bruno Martins

Research Associate

Sainsbury Laboratory
University of Cambridge
47 Bateman Street

Cambridge CB2 1LR
Office Phone: +44 (0)1223 761100

Research Interests

My main research interest is to gain a quantitative understanding of the design principles of genetic circuits and intracellular physiology. I am especially interested in how genetic circuits couple to one another and to other global cellular processes, such as the cell cycle and metabolism. Owing to stochastic variation, there is a growing realisation that this challenge must be tackled at the single-cell level in order to distinguish between different regulatory models.

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Bacterial micro-colony showing heterogeneity in expression of a gene reporter (green).
My present research at SLCU is centred on the circadian clock of the single-celled microbe Synechococcus elongatus, a freshwater cyanobacterium. Circadian clocks are gene circuits that regulate rhythmic expression in anticipation to daily cycles of sunlight. I use a combination of single-cell time-lapse microscopy, theoretical models and synthetic biology approaches to study the coupling of the clock to diverse intracellular circuits and dynamic processes, and reveal new cellular behaviours and principles of biological organisation.

 

 

 

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Cover of Molecular Systems Biology highlighting our work on frequency doubling (Martins et al. 2016, Mol Syst Biol), and showing the feedforward loop architecture of the gene circuit we characterised.
For example, by studying the coupling of the clock to a key photosynthetic promoter, I discovered an endogenous circuit that implements frequency doubling of oscillatory clock outputs. Using genetic and environmental perturbations, as well as mathematical modelling, I learned the design principles that make this circuit a potentially general mechanism for modulating the frequency of biological oscillators (Martins et al. 2016, Mol Syst Biol).

More recently, I studied the coupling of the circadian clock to the cell cycle and to cell size control. Using a phenomenological approach, I revealed how the clock modulates the rules of size control by continuously modulating the cell division rate throughout the day, both in constant and time-varying environments (Martins et al. 2018, PNAS). Read a news article on this research.

I am also interested in the potential of circadian clocks for synthetic biology. Rational designing of oscillators has been a pursuit of synthetic biology since its inception, but evolution has already endowed natural systems with extremely robust oscillators in the form of circadian clocks. Understanding how to systematically manipulate their frequency and how to integrate clocks with other pathways will enable the construction of more complex synthetic circuits.

 

 

Internal and external factors coordinating cell growth and divisions in cyanobacteria (Martins et al. 2018, PNAS)

 

Previous work

Before coming to Cambridge, I did a PhD in Peter Swain's lab at the University of Edinburgh, where I used mathematical modelling to gain insight into two simple, yet ubiquitous, sensing and transductions mechanisms: allosteric sensing and phosphorylation-dephosphorylation cycles. I studied the input-output dynamics of these mechanisms in terms of the fundamental constraints inherent in their design.

Key Publications

Bruno M.C. Martins, Amy K. Tooke, Philipp Thomas, James C.W. Locke, Cell size control driven by the circadian clock and environment in cyanobacteria, Proc Natl Acad Sci U S A, 115(48):E11415-E11424 (2018). https://doi.org/10.1073/pnas.1811309115

Bruno M.C. Martins*, Arijit K. Das*, Liliana Antunes, James C.W. Locke, Frequency doubling in the cyanobacterial circadian clock, Mol Syst Biol, 12:896 (2016). https://doi.org/10.15252/msb.20167087

Bruno M.C. Martins, Peter S. Swain, Ultrasensitivity in phosphorylation-dephosphorylation cycles with little substrate, PLoS Comput Biol, 9:e1003175 (2013). https://doi.org/10.1371/journal.pcbi.1003175

Bruno M.C. Martins, Peter S. Swain, Trade-offs and constraints in allosteric sensing, PLoS Comput Biol, 7:e1002261 (2011). https://doi.org/10.1371/journal.pcbi.1002261

 

Review

Bruno M.C. Martins, James C.W. Locke, Microbial individuality: how single-cell heterogeneity enables population level strategies, Curr Opin Microbiol, 24:104-12 (2015). https://doi.org/10.1016/j.mib.2015.01.003

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