Investigating the cross-talk between structural and immune component of human skin to understand pathogen sensing in cutaneous health and inflammation

Skills Priority Alignment: Quantitative Biology

Hypothesis
Molecular cross-talk between structural and immune components of the skin underpins individual differences in the pathogen sensing pathways of different inflammatory skin diseases.

Aims and Objectives
Aim 1:
Identify pathogen-sensing signatures in healthy skin. We will first characterise a specific pathogen-sensing signature in healthy human skin by single-cell Drop-Seq. This will provide a baseline signature that we can then track in the context of skin inflammation in order to understand the alterations and contributions of this signature to disease.

Aim 2:
Undertake deconvolution of whole skin transcriptome by in silico methods to identify the signature found using Drop-Seq that can be tracked in the context of different inflammatory states in the skin. High-level whole tissue analysis using the pipeline and tools developed in this project will enable re-exploration of data to determine the contribution of pathogen-sensing pathways to inflammation in the skin,

Aim 3:
Epigenetic modification of transcription of the bacterial sensing pathway and responses will be analysed to understand how chromatin state contributes to disease. We aim to conduct an integrated transcriptomic and epigenetic analysis of a signature identified in healthy controls then tracked in samples of inflammatory skin conditions.