Post Doctoral Research Assistant
Senior Lecturer in Structural Bacteriology
Biofilm development
Most bacteria form biofilms which enable persistence in extreme environments, contribute to pathogenicity and cost the NHS £2 billion each year to treat. Biofilms are communities of microorganisms encased in a self-produced matrix of extracellular polymeric substance (DNA, proteins, lipids, polysaccharides). This matrix protects the inhabitants from environmental pressures, other organisms and antibacterial compounds. We are interested in how these polymers provide interactions and stability within the matrix and we are currently studying several proteins that are important for Legionella pneumophila, Escherichia coli, Porphromonas gingivalis and Pseudomonas aeruginosa biofilm formation and maturation.
Mechanisms of bacterial secretion
Secretion systems are protein complexes present in the membranes of bacteria and mediate the formation of structures on their extracellular surface and transport virulence factors into the extracellular space or directly into their hosts during infection. We are interested in how the cargo of these systems are recognized during their secretion and the overall mechanisms of secretion. We are currently studying secretion by the L. pneumophila and E. coli type II systems (T2SS) and the P. gingivalis type IX secretion system (T9SS). We are also investigating the role of the P. gingivalis T9SS in the biogenesis of outer membrane vesicles.
Novel secreted bacterial proteins
Several substrates secreted by the L. pneumophila T2SS have been identified that bind to the bacterial surface but also to the cytoplasmic face of the Legionella replication vacuole within the host. This represents a new role for the T2SS and indicates that the spatial organization of type II substrates after secretion is extremely important for the virulence and persistence of L. pneumophila. Many of these substrates have unique amino acid sequences with specific functions in biofilm growth, adhesion, mucosal degradation, dampening cytokine output and sequestration of host vesicles to the replication vacuole. We are currently investigating the structure and function of these substrates/effectors to determine their role during infection.
Major Research Grants
2019-2022 MRC Research Grant (MR/R017662/1). Structural studies into novel membrane associated virulence factors of Legionella pneumophila. Applicant: James Garnett (PI). Amount to PI: £460,083
2017-2019 Academy of Medical Sciences Springboard Award (SBF002\1150). A multidisciplinary approach to identify new antibacterial targets within biofilms. Applicant: James Garnett (PI). Amount to PI: £99,924
2017-2020 Leverhulme Trust grant (RPG-2017-222). An integrated computational-experimental method to redesign protein dynamics. Applicants: Alessandro Pandini (PI), James Garnett (Co-PI). Amount to PI: £114,024
2015-2018 MRC New Investigator Research Grant (MR/M009920/10). Recognition by the type II secretion system and how it enables Legionella pneumophila to thrive. Applicant: James Garnett (PI). Amount to PI: £463,246