My fundamental interests lie in the gene regulatory networks that enable bacteria to adapt to both environmental and metabolic stimuli, in particular in relation to their interactions with plants. I use systems biology approaches (RNA-seq and targeted proteomics) to understand regulatory networks both in their naturally stimulated states and when perturbed using synthetic biology tools. I am particularly interested in how synthetic regulatory proteins can be used to both exploit plant-growth promoting bacteria and suppress those that act as pathogens.
Improving bacterial nitrogen fixation
My current research aims to re-engineer nitrogen fixing bacteria (‘diazotrophs’) for improved plant growth promotion and in turn reduce the dependence of agriculture on chemical fertilisers. We are using systems biology tools to investigate how hierarchical layers of regulatory control establish efficient nitrogen use in soil-dwelling bacteria (such as Klebsiella oxytoca and Azotobacter vinelandii), whereby the rates of nitrogen fixation (N2 to ammonia) and assimilation (ammonia to amino acids) are explicitly coupled (via master regulator proteins) to optimise ammonia metabolism. What we learn with respect to the key nodes of control and robustness will inform rational re-tuning of the regulatory network using synthetic transcription factors, with the aim of allowing excess ammonia to be released into the soil. This strategic BBSRC-funded project (BB/N003608/1) is led by Professor Martin Buck and Dr Jorg Schumacher, in close collaboration with both experimental and theoretical research groups from Imperial College, the Univeristy of Oxford and the John Innes Centre.
Regulation of virulence in plant pathogens
How plant signals are perceived by bacterial pathogens and integrated into decision making processes (involving global changes in gene expression) is both poorly understood and an exciting research avenue considering the promise of anti-virulence strategies for future crop disease management. My interests focus in particular on the regulation of the type-III secretion system (T3SS), a key virulent determinant in most bacterial pathogens. This needle-like protein structure injects virulence proteins into the plant cell in order to undermine the immune system and enable colonisation of the host. My PhD studies, funded by a BBSRC Doctoral Training Grant award, revealed that expression of the master transcriptional regulator of the T3SS gene set in Pseudomonas syringae, the HrpL σ factor, is fine-tuned via negative autogenous control. My current research focuses instead on the role of the post-transcriptional regulator CsrA/RsmA in both T3SS regulation and decision making on the plant host in general. Not only does this regulator appear to be associated with motility, virulence and the capacity to form biofilms, but the fact that three CsrA paralogues are expressed in Pseudomonas syringae raises fundamental questions with regard to the evolution of gene networks via sub-functionalisation.
et al., 2018, Mutualism between Klebsiella SGM 81 and Dianthus caryophyllus in modulating root plasticity and rhizospheric bacterial density, Plant and Soil, Vol:424, ISSN:0032-079X, Pages:273-288
et al., 2017, Functional Characterization of Key Residues in Regulatory Proteins HrpG and HrpV of Pseudomonas syringae pv. tomato DC3000, Molecular Plant-microbe Interactions, Vol:30, ISSN:0894-0282, Pages:656-665
et al., 2017, Evading plant immunity: feedback control of the T3SS in Pseudomonas syringae., Microbial Cell, Vol:4, ISSN:2311-2638, Pages:137-139
Schumacher J, Waite C, Wang B, Synthetic transcription factors allowtuneable synthetic control of the complex bacterial nor regulon, EMBO: Creating is Understanding: Synthetic Biology Masters Complexity
Schumacher J, Waite C, In vivo absolute and relative Nif protein abundances of Klebsiella oxytoca, 13th European Nitrogen Fixation Conference