Project 7

Mechanisms of neutrophil swarm initiation and resolution and consequences in inflammatory disease

ESR7: Nils Olijhoek

University of Sheffield, Department of Infection, Immunity & Cardiovascular Disease (United Kingdom)

Supervisors: Pr. S. Renshaw, co-supervisors: local: Dr P. Elks, external: academic: T. Vicsek (P5, ELTE)

Objectives: After tissue injury or infection, neutrophils responding to inflammatory signals release amplification signals that attract other neutrophils into “swarms”. The initiating events are poorly characterised and the mechanisms determining neutrophil retention in swarms and how these ultimately lead to dissolution are unknown. Aims: 1) elucidate the molecular events initiating neutrophil swarms; 2) establish the role of hypoxia signalling in influencing swarm initiation and resolution; 3) to determine the molecular signals retaining neutrophils within swarms and how these control swarm resolution; 4) to screen for new small molecule accelerators of swarm resolution.

Expected Results: 1) A complete molecular understanding of swarm initiation and resolution; 2) New insights into therapeutic targeting of neutrophil swarms in disease.

Secondments: Academic: P1 Montpellier: Dr G. Lutfalla, Month 24, 2 months: role of regeneration in zebrafish swarming, P8 ELTE: Prof. T. Vicsek, Month 37, 2 months, computational modelling of swarm dynamics. Industrial: P12 Acquifer, Dr. Jochen Gehrig, Month 30, 1 month, screening of small molecule regulators of swarming in vivo.