The glycome of emergency neutrophils and implications in sepsis

Research Project, 2019 – 2024

The glycome represents a next level of regulation after the genome and proteome to provide dynamic changes in biology. This project aims to explore the glycome and glycoproteome in human neutrophils during health and disease, more precisely in sepsis.
We hypothesise that the neutrophils have a unique regulation of glycome composition. Neutrophil granules that store bactericidal enzymes and receptors needed for the cells to fight off invading bacteria are formed step-wise during granulopoiesis. The glycans in each granule population may thus differ depending on the composition of the glycan-producing machinery at each differentiation step. This gains support from our studies of galectin-3, a lectin that activates neutrophils through interaction with glycoconjugates in one particular granule population only. In sepsis, an increased need for neutrophils launches ‘emergency granulopoiesis’ which speeds up neutrophil production and changes granule composition. We think that this process is associated with alteration in glycation towards simpler glycans, which could affect the progress and outcome of sepsis. We will perform a comprehensive characterization of the granule glycome in steady-state neutrophils to build a knowledge base for subsequent exploration of the glycome in emergency granulopoiesis during sepsis. This will help us to understand functional changes in septic neutrophils, and can be used in the development of tools for sepsis diagnosis and follow-up.