Research
Structural and Functional Glycobiology
The Boraston Laboratory was established in 2003 as part of an effort to build structural biology at the University of Victoria. Since then, the Boraston Laboratory has become known for using structural approaches to study the molecular basis of how proteins interact with and modify carbohydrates. However, to accomplish our goal of also illuminating the biological context of this, we also use a wide array of complementary approaches, ranging from genomics/transcriptomics to molecular biology to microbiology. A variety of national and international collaborations also enrich our ability to achieve our research goals and our training environment . More details about research projects are given below.
The Boraston Laboratory has a long history of studying enzymes that process the glycans found on glycoconjugates. This began with the study of enzymes deployed by Clostridium perfringens, a common inhabitant of the human and animal gastrointestinal tract, and the human respiratory pathogen Streptococcus pneumoniae. We have spent several years on the structural and functional examination of these enzymes. This has allowed us to synthesize this molecular level information into detailed views of glycan processing pathways, providing unique perspectives on the interaction of these microbes with their hosts (see here and here for reviews).
These bacteria are treasure-troves of interesting glycan processing enzymes, but some holes remain to be filled with respect to the potential of the bacteria to process some glycans. Current research in this area focuses on bioinformatics predictions and biochemical analyses to identify putative new glycan processing enzymes encoded in the S. pneumoniae genome, and investigating the specificities of certain glycan processing enzymes families that are expanded in C. perfringens.
More recently, our glycoconjugate processing enzyme research has moved to include unique peptidases that hydrolyze the peptide backbone of proteins but use post-translationally added O-linked glycans on the substrate as recognition determinants. These enzymes, which we call O-glycopeptidases, are typically found in host-adapted bacteria and likely play a role in mediating the interaction of the bacterium with its host. Our current research is probing how the sequence of the peptide substrate and the structure of the attached glycan contribute to how the substrates are recognized by these peptidases, and, in turn, how structural variation in the large O-glycopeptidase family influences recognition of diverse substrates.
Glycoconjugate Processing
Glycan processing pathway in Streptococcus pneumoniae. From Hobbs et al.
The O-glycopeptidase ZmpB from Clostridium perfringens. From Pluvinage et al.
An O-glycopeptidase active site (unpublished).
Biomass Processing
Carrageenan processing pathway in Pseudoalteromonas fuliginea PS47. From Hettle et al.
In both the marine and land environments carbon is trapped primarily in the cell wall and storage polysaccharides of algae and plants. The turnover and recycling of this carbon is facilitated by the metabolic action of microbes. The bacterial depolymerisation of terrestrial plant cell-wall polysaccharides, cellulose being the major example, has been intensely studied for over 50 years and it is therefore well understood. The same is not true of marine polysaccharides. The cell walls of seaweed are composed of a group of complex and unusual polysaccharides that comprise up to ~50% of the dry mass. These polysaccharides are chemically and structurally different from those of terrestrial plants as they often contain, in red algal galactans for example, sulphate groups, L-sugars, and anhydrosugars that are not present in terrestrial plants. Understanding the biochemical basis for the turnover of carbon in algal biomass is key to, for example, the development of complete biogeochemical models of the global carbon cycle and to unlocking farmable seaweed biomass feedstocks for the generation of biofuels or other high-value products.
The vision that drives our research into how microbes utilize algal polysaccharides is to define the molecular features of the distinctive metabolic systems that enable bacteria to metabolize the wide variety of marine polysaccharides.
The long-term goal is to leverage this information to better understand carbon turnover in the oceans as well as to improve the use of marine polysaccharides in a variety of applications.