Titre : “The Bottom Half of the Periodic Table and Mass Cytometry; New Probes for Chemical Biology”

Endroit : Pavillon J.-Armand Bombardier, salle 1035 à 11 h.

Hôte : Professeure Joëlle Pelletier

Cette conférence sera prononcée (en anglais) par le Professeur Mark Nitz du département de Chimie de l'Université de Toronto.

Résumé : Mass Cytometry (MC) offers unparalleled potential for the development of highly parameterized cellular assays. Current reagents compatible with MC analysis mainly employ antibody-metal-chelating polymer conjugates that are used to stain samples ex-vivo and report on the presence of biomarkers. Here, we expand the dimensions of MC experiments by developing the first activity-based probes designed specifically for use with the technology.  A compact MC-detectable fragment containing tellurium has been generated that can be conjugated to a variety of activity probes to target biological processes such as enzyme activity, metabolism or transport. In a key example of the potential of this approach we report a series of tellurium containing isotopologous probes for cellular hypoxia compatible with Mass Cytometry (MC). Sequential labelling with the isotopologous probes (SLIP) of pancreatic tumour xenograft models revealed changes in cellular oxygenation over time which correlated with the distance from vasculature, the proliferation of cell populations, and proximity to necrosis. SLIP allows for capture of spatial and temporal dynamics in vivo using activity-based probes.  The reagents and strategy described will provide a general approach to the development of a large toolkit of MC-compatible probes for activity-based profiling of single cells.

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