The digital monocyte

Aim: To describe the functions of different monocyte phenotypes. To identify the molecular switches determining monocyte phenotypes. Explore conditions able to switch phenotype.

Background: During certain conditions, such as sepsis, trauma and cancer, a lost balance between immunosuppressive and proinflammatory mechanisms contribute to mortality and morbidity. A major contributing factor is changes in the monocyte compartment. Recent studies have shown that these changes are dynamic and plastic, but the molecular details and mechanistic understanding are largely unknown. Currently, the project is focusing on two distinct phenotypes namely the immunosuppressed response which is weaker compared to normal and the trained immune response where cells are highly responsive to secondary stimulus, two opposite sides of the normal response. 

Outcomes: By combining in vitro models of different monocytic phenotypes (e.g. trained, normal or suppressed) with mechanistic modelling, the project hopes to generate an overarching model describing monocyte responses, ranging from initial stimulation to functional output. By formalising the knowledge gained in the cell models in mechanistic, dynamic in silico models, we hope to be able to predict and influence monocyte behaviour to direct future immunotherapies.