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Abstract:

Our immune cells take cues from the environment to guide their responses. One important type of biomolecule that immune cells use to differentiate ‘good’ from ‘bad’ are the complex carbohydrates that decorate the outside of our own cells or of pathogens, the structures of which are necessarily very different. The ability to sense these carbohydrates takes place through glycanbinding proteins (GBPs) that can either stimulate or repress immune cells. Siglecs are one such family of GBPs expressed on our immune cells, and through interactions with their sialic acidcontaining glycan ligands, they play fundamental roles in immune homeostasis. As sialic acid is rarely present on pathogens, Siglecs recognize ‘self’ and – not surprisingly – act as a ‘brake’ to prevent inappropriate immune responses against our own tissues. Given that the function of Siglecs is dictated by interactions with their sialic acid ligands, a deeper knowledge of these ligands is needed to better understand how these complex structures are altered in disease such as cancer and autoimmunity, and to develop new strategies to modulate immune cell function for therapeutic benefit. Studying Siglec-glycan interactions is challenging due to the low affinity at which they recognize their glycan ligands, as well as the heterogeneity of cellular glycans. Our laboratory is developing approaches that are compatible with both of these challenging features. Specifically, we are developing new approaches to study Siglec ligands, including: (i) a mass spectrometrybased assay to quantitatively dissect the natural repertoire of glycans on cells and (ii) a chemical genetics strategy to assess the enzymes responsible for creating the ligands for individual Siglecs. Accelerating these efforts are a new toolbox of soluble Siglecs that have been created and validated. Progress towards implementing these approaches will be presented for a number of Siglec recently implicated as important next-generation targets in immuno-oncology.

Bio:

Trained as a biochemist, Dr. Macauley carried out his PhD with Professor David Vocadlo, at Simon Frasier University, using chemical biology to tackle roles for glycosylation. This interest was further developed during his Postdoctoral research with Professor James Paulson, at The Scripps Research Institute, where Dr. Macauley developed an expertise in glycoimmunology. For the three years prior to joining the University of Alberta, Dr. Macauley has been an Assistant Professor at The Scripps Research Institute where he has been developing projects that he is excited to carry on at University of Alberta. Dr. Macauley is a tier II Canada Research Chair in Chemical Glycoimmunology, and loves to research, teach, and mentor in this area.