I completed my Ph.D in Biochemistry in 2016 at the University of Cambridge, under the guidance of Professor Christopher Howe and Dr Andrew Spicer of Algenuity. Together with collaborators, the Howe lab has pioneered the development of biological solar cells, which are able to produce current as a result of photosynthetic activity in cyanobacteria. I then joined Professor Patricia Harvey’s laboratory to work on the D-factory project, which aims to set up a sustainable CO2 algal biorefinary utilizing the algae Dunaliella. While there I also contributed to a European Commission report ‘food from the oceans’ as part of a high level group of scientific advisors. I have now returned to Chris Howe’s lab as part of the OpenPlant Project. The goal of this project is to create an overexpression system for transgenes that is sensitive to changed in electropotential.
I obtained my PhD in Cell Biology from the University of Edinburgh, mentored by Prof. Jean D Beggs. During this time, I was interested in the spliceosome cycle, in the connection between splicing and transcription, and also in how proofreading factors help to prevent error in splicing. I spent a significant amount of time using the auxin-inducible degron to conditionally deplete essential proteins, and finding ways to improve this depletion system to get a faster and more tightly-controlled response.
My desire to embark on plant synthetic biology, while maintaining an interested in splicing and conditional expression systems, lead me to join the Plant Metabolism Group of Prof. Alison Smith in October 2017, to develop riboswitches as molecular tools to control transgene expression in algae, higher plants and other eukaryotes. The ultimate aim of this project is to develop novel inducible systems for metabolic engineering applications or as in vivo sensors of metabolites.
I am a post-doctoral researcher in James Locke's group at the Sainsbury laboratory. I am interested in how cells discriminate between different environmental states, integrate dynamic outputs from different gene circuits, and make decisions. In my current research, I use a combination of theory and time-lapse microscopy experiments to understand the dynamical coupling of the cyanobacterial circadian clock to other networks, in both endogenous and synthetic systems.
Circadian clocks are a class of networks that regulate rhythmic expression in response to daily cycles of sunlight. A large fraction of all genes in the cyanobacterium Synechococcus elongatus are clearly under circadian control. Recently, I studied the coupling of the clock to a circuit that controls expression of the gene psbAI. Genes regulated by the clock typically peak once a day, either at dawn or at dusk. However, under conditions of constant low light, I observed a doubling of the frequency of expression of psbAI, i.e., its expression peaks twice a day. Using genetic and environmental perturbations, I found these dynamics can be modulated: either single-peak or two-peak expression can be generated. Using an iteration of modelling and experiments, I then determined the network design principles underlying the dynamics of frequency doubling.
In electronics, clock signals are essential elements of complex circuits, allowing different components of the circuit to be linked and synchronised. In biology, clocks likely play a similar role. Rational designing of oscillators has been a pursuit of synthetic biology since its inception, but evolution has already endowed natural systems with extremely reliable and robust oscillators in the form of circadian clocks. If we can understand how to harness clocks to generate specific (non-circadian) frequencies, and how to systematically integrate clocks with other pathways, we could gain a powerful tool to enable the construction of more complex synthetic circuits.
Before coming to Cambridge, I did a PhD in Peter Swain's lab at the University of Edinburgh. In my PhD 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.
Francisco J. Navarro's work focuses on the function of small RNA (sRNA) molecules and their use as regulatory elements in synthetic gene circuits. sRNA molecules most likely evolved as a defense mechanism against viruses and retro-transposons, and were co-opted for fine-tuning of gene expression. Their small size and predictable targeting rules make them perfect tools for regulating gene expression in synthetic gene circuits. This project is carried out in the green alga Chlamydomonas reinhardtii, which is amenable to genetic manipulation and a model organism for key plant processes, such as photosynthesis. With an sRNA pathway that resembles that of higher plants, Chlamydomonas allows the testing of proof-of-principle small RNA-based genetic devices before extrapolating to other plant species.
Francisco completed his PhD in the laboratory of Prof. Jose Manuel Siverio (University of La Laguna, Spain), studying nitrate assimilation in Hansenula polymorpha, a methylotrophic yeast with important biotechnological applications. This was followed by a postdoc in the laboratory of Sir Paul Nurse, first at The Rockefeller University, USA, and then at the London Research Institute, on cell size control and regulation of gene expression by RNA-binding proteins. Through systematic screening of a gene deletion collection of the fission yeast Schizosaccharomyces pombe, he identified a set of novel genes involved in the coordination between cell growth and cell cycle progression. In 2015, he joined the laboratory of Sir David Baulcombe in the Department of Plant Sciences, University of Cambridge.
Francisco’s research interests concern questions regarding global regulation of gene expression and limits of cell growth. These questions are relevant to synthetic biology because synthetic gene circuits are embedded into the cell’s own gene network, and so their activities are not insulated from global cell regulation. He believes that microorganisms, like Chlamydomonas, will continue to be useful research models to uncover new exciting biology, and contribute to the advancement of synthetic biology. The fast growth of unicellular algae, in addition to a range of recently developed tools and resources, are making these organisms an interesting chassis for synthetic biology, with industrial applications in the biopharming sector.
He is also a collaborator of Café Synthetique, an informal monthly meetup with public talks that brings together the Cambridge synthetic biology community
My research involves using synthetic biology and evolution for improving agricultural traits, more specifically to improve photosynthesis. As the world population continues to expand, it is predicted that crop yields will have to increase by 50% over the next 35 years. Traditional breeding programs cannot keep pace with this current population growth rate. Plant biomass is produced by carbon dioxide (CO2) fixed by the enzyme Rubisco during photosynthesis.
This process known as C3 photosynthesis can be very inefficient as Rubisco also interacts with Oxygen (O2) in a wasteful process known as photorespiration. In order to increase yields, photorespiration should be reduced considerably. Fortunately, some plants have evolved such mechanism already. C4 photosynthesis results from a series of anatomical and biochemical modifications in the leaf that lead to photosynthesis being compartmentalized between mesophyll and bundle sheath cells. This division of labour generates a CO2 enriched environment where photorespiration is effectively abolished. C4 plants therefore produce more yield and use water and nitrogen more efficiently. The fact that C4 photosynthesis has evolved independently in more than 60 lineages allows us to think it is possible to engineer C4 photosynthesis in C3 plants. In order to engineer this trait, cell specific genetic circuits need to be developed. Unfortunately there is a limited number of genetic parts driving cell specificity in leaves. My main objective in OpenPlant is to generate a library of leaf specific motifs that can be used to drive the expression of both nuclear and plastid encoded genes in specific compartments and specific cells of leaves.
Together with colleagues in the Department of Plant Sciences, Department of Chemistry and the Department of Physics I am part of an OpenPlant fund project that aims to use microfluidics for high-throughput analysis of genetic parts. We hope to generate a whole toolbox of parts that are useful to rewire different traits.
Plants produce a wide variety of specialised metabolites. These molecules play key roles in the interaction of plants with their biotic and abiotic environment. In addition to their ecological functions, plant-derived specialised metabolites are major sources of pharmaceuticals and other high-value compounds.
Recently, it was discovered that the genes for the biosynthesis of several major classes of these compounds are physically co-localised in so called ‘gene clusters’ in plant genomes. Such clustering of non-homologous genes contrasts the expected arrangement of genes in eukaryotic genomes. The co-localisation of functionally-related genes enables the formation of fundamentally different mechanisms of gene regulation in comparison to the control of dispersed genes. The purpose of this project is to improve our understanding of the transcriptional control of plant metabolic gene clusters. The focus within OpenPlant will be on chromatin related regulatory processes that govern the expression of gene clusters. By chromatin immunoprecipitation, chromosome conformation analyses and genome engineering we aim to characterise the chromatin environment at gene clusters and its impact on cluster regulation. The findings of this project will open up new opportunities for the discovery and engineering of metabolic pathways using genetic and chemical approaches. They will also underpin synthetic biology-based approaches aimed at refactoring of plant metabolic gene clusters and the development of synthetic traits.