Lab website: https://www.lea-smithlab.uk/

Google scholar profile

My laboratory focuses on bacterial cell biology, developing synthetic biology toolsets and methods for genetic engineering of a broad range of Gram positive and negative bacteria, using bacteria (particularly cyanobacteria) for synthetic biology applications, notably carbon capture, compound production and natural products discovery, and characterising the role of microbes in global biogeochemical cycles.

Synthetic biology achievements:

• Developed the most comprehensive Golden Gate cloning based toolsets for cyanobacteria, including the fastest growing species identified to date, Synechococcus PCC 11901 (Vasudevan et al, 2019; Victoria et al, 2023).
• Partial development of a BBSRC funded mutant library targeting nearly every gene in the cyanobacterium, Synechocystis PCC 6803, using the automated robotic facilities at the Edinburgh/Earlham DNA foundries. To date, we have produced more than 1500 plasmids and 600 mutants. 
• Developed genetic manipulation tools for precise and repeated genetic engineering of Alcanivorax borkumensis SK2, an important hydrocarbon degrading bacteria (manuscript in preparation).
• Developed genetic manipulation tools for Alcanivorax TEM35, isolated from the bottom of the Mariana Trench (11,000 metres depth). This is the first deep-sea microbe for which genetic tools have been developed and will be used to understand how microbes withstand high pressure environments (manuscript in preparation).
• Demonstrated rapid growth of Synechococcus PCC 11901 is maintained at different light intensities (Cho et al, 2023).
• Developed and refined a system to generate unmarked mutations in Synechocystis PCC 6803 (Lea-Smith et al, 2013, 2016).
• Developed Synechocystis PCC 6803 mutants with increased hydrogen production and electrical output in biological photovoltaic devices, a 'battery' powered by microbial electron export which could be used in small electrical devices (Bradley et al, 2013; McCormick et al, 2013; Saar et al, 2018, Wey et al, 2021).
• Developed a system to generate unmarked mutations in the purple non-sulfur bacterium Rhodopseudomonas palustris, a species with multiple potential bioremediation applications (Du Toit et al, 2021).

System biology achievements:

• Determined the location of over 1,700 proteins in Synechocystis PCC 6803, using subcellular fractionation and quantitative proteomics, resulting in the most detailed map of the proteome in this species or any other bacterium. This was the first example of this technique being applied in a bacterial species (Baers et al, 2019).
• Completed the most comprehensive review of cyanobacterial metabolism (Mills et al, 2020).
• Completed the most comprehensive review of cyanobacterial electron transport (Lea-Smith et al, 2021).
• Curator of the Synechocystis PCC 6803 BioCyc Pathway/Genome Database (manuscript in preparation).

Other achievements:

• Conducted the most thorough investigation of microbial populations in the Challenger Deep in the Mariana Trench, the deepest known location in the ocean. We identified a novel population of hydrocarbon degrading bacteria and biological synthesis of C16, C18 and C20 alkanes, which suggested a new biosynthetic pathway (Liu et al, 2019). In the same samples, we demonstrated that polysaccharide utilization varied between bathypelagic and hadal waters, supporting different microbial populations (Zhu et al, 2023).
• Characterised the functional role of hydrocarbons in cyanobacteria (Lea-Smith et al, 2016). With funding from HFSP we have demonstrated hydrocarbons induce membrane curvature by aggregating in the centre of the membrane lipid bilayer and are required for membrane remodeling.
• Proposed the existence of a novel, large-scale biogeochemical cycle, the 'short term hydrocarbon cycle', in which 300-800 million tonnes per annum of cyanobacterial/algal produced hydrocarbons are rapidly degraded by bacteria, sustaining a microbial population in non-polluted waters that can expand to degrade oil spills (Lea-Smith et al, 2015). This cycle has recently been confirmed by oceanographic data recently published in Nature Microbiology.
• Determined the role of terminal oxidase proteins of the photosynthetic/respiratory electron transport chain in Synechocystis PCC 6803 under different environmental conditions (Lea-Smith et al, 2013; Ermakova et al, 2016).
• Established that decreasing light harvesting in Synechocystis PCC 6803 by reducing the light harvesting complex did not increase biomass productivity of dense cultures, except under conditions of low carbon (Lea-Smith et al, 2014).
• Characterised the enzymes catalysing the final step of mycolic acid (a long chain lipid incorporated into the cell wall) biosynthesis (Lea-Smith et al, 2007) and the second mannosylation step of phosphatidyl mannoside and lipoarabinomannan biosynthesis (Lea-Smith et al, 2008), and a mycolic acid transporter (Yamaryo-Botte et al, 2014). All enzymes are potential drug targets for anti-tuberculosis drugs.