Structural analysis of Siglec receptors
Jahnavi Jangala, Catarina S. Silva, Madalen Le Gorrec, Maria Bacia, Ambroise Desfosses, Irina Gutsche
This project is a part of the Glytunes Innovative Training Network involving seven European academic research groups and four industrial partners, and driven by 14 PhD students. Siglecs are transmembrane receptors expressed on surfaces of innate immune cells. They recognise sialic acids used by vertebrates as signatures of “self” but also by some microbial pathogens that thereby modulate host immune responses. Aberrant interactions between Siglecs and their ligands lead to a variety of pathologies including infection, autoimmune diseases and cancer. The global aim of the Glytunes consortium is to understand and exploit the Siglecs-glycans cross-talk by harnessing the synergy of combining chemical, biological, biophysical and immunological research strategies and ultimately translating this knowledge into novel diagnostics and therapeutics.
In our group, we use cryo-EM to solve the 3D structure of human Siglec-10, and further characterize this receptor in vitro and in cellula through biochemical and biophysical approaches. This work should help understanding the structural basics of Siglec-10 binding to its ligands, which is crucial towards the rational design and development of novel therapeutic and diagnostic strategies against cancer.
Collaborations:
– June Ereño-Orbea, CICbioGUNE, Bizkaia, Spain
– Thomas Boltje, Radboud Universiteit, Nijmegen, Netherlands