{"id":110,"date":"2015-11-09T20:18:14","date_gmt":"2015-11-09T20:18:14","guid":{"rendered":"https:\/\/lab.research.sickkids.ca\/howell\/?page_id=110"},"modified":"2018-04-19T09:44:43","modified_gmt":"2018-04-19T14:44:43","slug":"gag","status":"publish","type":"page","link":"https:\/\/lab.research.sickkids.ca\/howell\/molecular-mechanisms\/exopolysaccharides\/gag\/","title":{"rendered":"GAG"},"content":{"rendered":"
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Model of GAG\u00a0biosynthetic machinery<\/p>\n<\/div>

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Aspergillus fumigatus<\/em> is a ubiquitous filamentous fungus that causes invasive lung infections in immunocompromised patients. Treatment of these infections using current antifungals is challenging and the mortality of invasive aspergillosis remains over 50%. During pulmonary infection the fungus grows as a biofilm within the lung tissue. The protective biofilm matrix allows the fungus to both adhere to the host cells as well as evade the immune system. Galactosaminogalactan (GAG) is an integral part of the A. fumigatus<\/em> biofilm matrix. This exopolysaccharide is a linear heteropolymer of \u03b1-1,4-linked galactose (Gal) and N<\/em>-acetylgalactosamine (GalNAc). The polymer is partially deacetylated after export and this modification is critical for biofilm formation and fungal virulence.<\/p>\n

Our collaborator, Dr. Don Sheppard (McGill University)<\/a> has identified a cluster of 5 co-regulated genes that are predicted to encode the proteins required for GAG biosynthesis. We have begun to characterize these proteins using in vivo <\/em>and in vitro<\/em> techniques. Characterization of Sph3 revealed that this protein is a glycoside hydrolase whose activity is essential for GAG biosynthesis and biofilm formation. Our results have enabled us to define a new family of glycoside hydrolases, GH135, and to suggest a role for the previously uncharacterized spherulin-4 family of proteins.<\/p>\n<\/div>

Current projects<\/h2>\n

Ongoing projects are focused on:<\/p>\n