Dissecting inflammation and spinal cord lesion site development at single-cell resolution
Funded in: 2021, 2022, 2023
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Problem: No deep understanding of the role of immune cells
Target: Study immune cell signalling, cell-cell interactions and wound healing
Goal: Discover key genes and pathways that drive wound healing and repair
The molecular era and a more concerted research effort around the globe has accelerated our understanding of what happens to the spinal cord once it becomes injured, and also what contributes to its regenerative failure. However, many questions do remain, including around the role of inflammation, which traditionally has been seen as damaging and detrimental to recovery. It is important to recognise though that an inflammatory phase is playing a crucial part of any successful tissue regeneration process. During this phase, the wound is cleared of debris whilst the molecular signals released by immune cells also initiate a proliferative repair phase. Without this, healing is impaired and/or cannot occur. On the flip side, excessive and/or non-resolving inflammation negatively interferes with repair, promoting scar tissue formation. The latter is what appears to happen following SCI, although why this is so remains incompletely understood. In order to find a cure for SCI, this knowledge gap must be addressed, ensuring that the inflammatory response aids repair and does not derail into one that contributes to scarring and regenerative failure.
A deep understanding of how immune cells co-exist in the injured spinal cord, how they influence each other’s behaviour and also that of other cells at the lesion site is currently lacking. To tackle this issue, the scientists will use the latest genetic and pharmacologic approaches to label, track and/or deplete select subsets of immune cells after SCI, also employing the most advanced sequencing technologies (spatial transcriptomics) and bioinformatics analyses to study immune cell signalling, cell-cell interactions and wound healing in the injured spinal cord.
The researchers` goal is to build a spatially resolved map of all the cell types and their interactions in the injured spinal cord across time. They will also use targeted manipulations to discover key genes and pathways that drive wound healing and repair, unlocking avenues for new and effective therapies to be developed.