Project Reference: TRG27-PDN-MS1

Project title: Investigating neutrophil-hematopoietic stem cell communication in cancer

Project outline

Our lab is interested in how immune cells move and interact with each other to mount immune responses. We focus on innate immune cells (neutrophils and macrophages) which provide the first line of defence against infections.  A recent focus is how these cells communicate to generate ‘innate immune memory’, a process under which innate immune cells and their progenitor stem cells acquire epigenetic changes during infections, leading to long-lasting improved reactions to later infection. How hematopoietic progenitors are educated by infection experience is unclear. Ongoing work from the Sarris lab indicates that experienced neutrophils can migrate from microbe-infected tissues to hematopoietic compartments and instruct the reprogramming of progenitors. 

Despite the evolutionary advantages in infection preparedness, immune memory can be maladaptive in chronic diseases. Chronic exposure to western diet, allergens and other factors can lead to perpetuated stimulation and reprogramming of hematopoietic stem cells. Cancer cells can conversely reprogramme hematopoietic compartments in ways that support tumour growth. However, it is unclear how cancer lesions communicate with remote hematopoietic organs. Based on our findings, we hypothesise that tumour-conditioned neutrophils may disseminate from cancer loci to hematopoietic sites and that these may influence the properties of hematopoietic progenitors. To address this, the project will develop cancer models in zebrafish and combine these with established pipelines to trace the migration of innate immune cells, visualise their real-time behaviour using advanced light microscopy and profile the transcriptomic and epigenetic profiles of cells using multi-omics. 

Principal Supervisor

Professor Milka Sarris

Email address: ms543@cam.ac.uk

Department / Partner Institute: Physiology, Development and Neuroscience (PDN)

Website: https://www.pdn.cam.ac.uk/people/milka-sarris

BBSRC strategic theme

Understanding the rules of life