Environmentally-regulated genes as venue for the discovery of new anti-inflammatory and bactericidal therapies (360G-Wellcome-211608_Z_18_Z)

Like many other immunological processes, inflammation is ‘plastic’ and is controlled by a wide range of factors including external conditions such as diet, socio-economical status and lifestyle. Using the Enriched Environment (EE) as model of ‘wellbeing’ and positive emotional state the host lab has shown that mice housed for 2-week in EE show an enhanced capacity to mount a pro-resolving and positive inflammatory responses and can clear bacterial infections more effectively (for more details see the full studies by Rattazzi et al. and Brod et al.).. Microarray analysis of whole blood taken from mice exposed to EE has identified a unique gene fingerprint with 8 genes being specifically up-regulated.Among the genes identified, 4 genes: Chil1 (Chitinase-3-like protein 1, CHI3L1), SRBP1A (Signal-regulatory protein beta 1A), S100A8 and S100A9 were found to be associated with an efficient inflammatory response and an increased bacterial clearance thereby contributing to host protection. Using molecular modelling we have identified new compounds that will act as agonists of the molecules described above and hence provide the same pharmacological effects of 2-weeks of ‘wellbeing’. The aim of the vacation scholarship will be to evaluate the effects of 12 new molecules (3 for each gene) on chemotaxis and phagocytosis.