Pathogens have evolved a multitude of strategies to evade host detection and propagate with in a host, from host cell mimicry or processing their own essential proteins. Our lab resolves these mechanisms to an atomic resolution, to reveal vulnerabilities for new therapeutic strategies.


X-ray structure of polysialytransferase (PST), the bacterial enzyme that helps assemble the polysialic acid capsule used by pathogens such as N. meningitidis to hide from phagocytosis and antibody recognition. - Lizak et al. (2017), Nature Scientific Reports.

One family of proteins involved in this strategy are glycosyltransferases, enzymes involved in the biogenesis of cell-surface glycans, especially the subfamily of sialyltransferases. Sialic acid, commonly found at the terminal position of glycoconjugates including glycolipid and glycoproteins, activates a multitude of biological functions through specific recognition of carbohydrate receptors in mammals. We are interested in the mammalian enzymes responsible for the addition of sialic acid to cell-surface glycans. These have been shown to be important in development, the correct functioning of the immune system and also in numerous pathological conditions including tumourgenesis and several neurological conditions.

Remarkably, many pathogens have evolved to take advantage of host surface-exposed sialic acids. In bacterial pathogens such as Neisseria meningitidis or Campylobacter jejuni this is evident in an invasion mechanism involving mimicry of either the polysialic acid structure on host neural cell adhesion molecules or the carbohydrate moieties of human gangliosides respectively, which effectively camouflages the bacteria from the human immune system.

Hydrogen bonds common to all cut site sequences withing the Mpro binding pocket. C5 autoprocessing sequence shown in purple for reference. - Lee et al. (2022), Nature Communications.,

While glycan mimicry allows bacterial pathogens to hide, some viral pathogens instead require specialized protein processing for their proteins to become in functional; in SARS-Cov-2, is done by the protease MPro. With ultra-high-resolution data from the Advanced Photon Source, our lab was the first to capture the cleavage reaction of this viral protease. Mpro cleaves SARS-CoV-2 polyproteins at eleven distinct sites in a series of processing events necessary for viral assembly and maturation. We determined the crystal structures of Mpro bound to ten of the eleven cleavage sites, providing a near complete structural picture of how this protease recognizes it's targets, creating a resource for antiviral drug design against COVID-19.

Selected Publications