Neutrophil heterogeneity in inflammation: scope for selective targeting? (NDORMS-2017/2)

Project Overview:

Our recent studies demonstrated that neutrophils play a central role in the initiation and perpetuation of aberrant immune responses and organ damage and that modulation of their numbers and functions by two independent approaches (IRF5 inhibition (1) or treatment with IFN-lambda (2)) leads to significant improvement in the pathogenesis of inflammatory arthritis and other forms of acute inflammation. We and others have also demonstrated the suitability of genomic analyses to neutrophil characterisation.
Given the largely pathogenic role of neutrophils in inflammatory diseases, our overall goal is to understand how neutrophils are recruited, activated and function in sterile inflammation, while uncovering novel molecular pathways through the state-of-the-art genomic screening approaches (3). This is important for understanding the neutrophil-intrinsic reprogramming of functional state in the inflamed tissue. The findings will have translational implication for the development of therapeutics for inflammatory diseases based on the reduction of immunopathogenic neutrophilic responses. As an example of selective targeting, the project will ascertain which specific aspects of neutrophil function are affected by treatment with IFN-lambda.

Training Opportunities:

The Kennedy Institute is a world-renowned research centre and is housed in a brand new state-of-the-art research facility. Full training will be provided in a range of functional genomics approaches (RNA-Seq, ATAC-Seq, ChIP-Seq, CyTOF), cellular techniques (cell isolation, tissue culture, FACS, CyTOF) techniques and animal models of inflammation under supervision of Prof Udalova and with support of other members of the group. Subject-specific training will be received through the groups’ weekly meetings. A core curriculum of 20 lectures will be taken in the first term of year 1 to provide a solid foundation in immunology, inflammation and data analysis. Students will attend weekly departmental meetings and will be expected to attend seminars within the department and those relevant in the wider University. Students will also attend external scientific conferences where they will be expected to present the research findings.