SCELSE Seminar Series: Rewiring the pneumococcal capsule pathway for investigating glycosyltransferase specificity and genetic glycoengineering

Abstract:
Virtually all living cells are covered with glycans and glycoconjugates, which are important for many biological functions like cell-cell recognition and biofilm formation. Their structures are primarily controlled by the specificities of glycosyltransferases (GTs). However, what defines their specificities remains poorly understood. Here, we developed a genetic glycoengineering platform by reprogramming the capsular polysaccharide pathways in Streptococcus pneumoniae to interrogate GT specificity and manipulate glycan structures. Constraints of the glycoengineering platform could be partially alleviated when the specificity of the precursor transporter was reduced. We also produced several medically important glycans, as well as demonstrated the importance of glycosidic linkages in binding to lung epithelial cells. Our work provided mechanistic insights into GT specificity and a novel approach for investigating glycan functions.

Biography:
Dr. (Chris) Sham Lok-To is an Assistant Professor at the National University of Singapore (NUS). He is the recipient of the Singapore National Research Foundation Fellowship, Class of 2019. In addition, Chris serves as the elected vice president of the Singapore Society of Microbiology and Biotechnology and the Deputy Research Director of the Infectious Diseases Translational Research Programme, NUS. Research in his laboratory aims to elucidate the mechanism by which bacteria assemble their cell envelope. In particular, his team is interested in the capsular polysaccharide (CPS) of Streptococcus pneumoniae because it is the target of all clinically relevant vaccines for this organism. Using a multi-disciplinary approach, his laboratory addressed fundamental questions regarding the synthesis and regulation of CPS synthesis, rewired the pathway to make customized glycans, and elucidated the role of CPS in host-pathogen interactions. Filling these knowledge gaps will inform the development of new vaccines and therapeutics that target the CPS layer.

Speaker:
ASSISTANT PROFESSOR CHRIS SHAM
Department of Microbiology and Immunology, NUS