Pascal Gagneux

Causes and Consequences of Glycan Evolution

Glycans are diverse and variable saccharide chains attached to proteins and lipids. Glycans can differ by species, individual, cell type, and even physiological state or developmental stage. Glycan variation influences many phenotypes: from cellular recognition during fertilization and development, to infection, immunity, and cancer. So far, we know little about the evolutionary forces that shape glycan variation. This is an important gap in our knowledge, because glycans are central to cellular recognition, and to human health and disease.

The Gagneux lab studies the roles of glycans in reproduction and infection.

Sperm-Female Interactions

As a paradigm of cellular recognition, we study how mammalian sperm interact with the female reproductive tract. In mammals, fertilization is internal and requires that sperm survive inside the female until they reach the egg. We aim to understand how sperm interact with the female and her immune system via their surface glycans. Studying how glycans promote female tolerance and allow fertilization promises new understanding of cellular recognition mechanisms and the molecular basis of reproductive incompatibility.

Host-Pathogen Interactions

Pathogens exploit glycans to gain entry into host cells. This conflict, and the measures that evolve in response, are visible in the diversity of host and pathogen glycan phenotypes. Viruses and bacteria often use glycan binding proteins to recognize and attach to host tissues. In return, hosts cover their external surfaces with secreted mucins that can act as protective decoys. Conversely, glycans on microbes can be targeted by the host using an array of innate immune system lectins. Many microbes evolve surface glycans that mimic the form of host glycans to hide from host immune responses.

The diversity and rapid evolution of glycans are likely outcomes of synergistic and antagonistic interactions during reproduction and infection