Successful long-term tissue regeneration of any human organ beyond the experimental state remains elusive. Given that the immune system plays a key role in tissue regeneration, including in the CNS, one of the most promising novel approaches is to integrate endogenous immune mechanisms into regenerative strategies. Specific knowledge of the fundamental cross-talk between immune mechanisms and the regenerating tissue is therefore needed to develop this approach into regenerative therapies.
This PhD project investigates how our own immune system can promote tissue repair in the brain and spinal cord. Using a wide range of in vitro and in vivo models the PhD student will determine the underlying immune mechanisms that promote brain repair and will establish how these mechanisms can be used therapeutically. This project has a strong translational angle and aims to benefit patients with Multiple Sclerosis and other neurodegenerative diseases.
In Multiple Sclerosis (MS), myelin, the coating around nerve fibres is destroyed resulting in neurodegeneration. Damaged myelin can be functionally reinstated by remyelination that involves recruitment, proliferation and differentiation of oligodendrocyte progenitor cells, generation of new myelin by differentiated oligodendrocytes and the re-sheathing of nerve fibres with new myelin. To date we have no means to initiate or enhance remyelination therapeutically and therefore cannot prevent neurodegeneration once myelin is lost.
The differentiation of oligodendrocyte progenitor cells into myelin-generating oligodendrocytes has been identified as the major bottleneck that prevents efficient myelin repair in MS patients. Using immune mechanisms to stimulate this regenerative cascade could be a novel way to overcome this block and boost remyelination. Inflammasomes as the guardians of the body are first in line to respond to tissue damage. They are essential for activating the immune response that reinstates homeostasis but their role in tissue repair is unknown.
Building on our preliminary data and using a wide range of models (see Dombrowski 2017 Nature Neuro) as well as molecular, immunological and computational approaches the PhD student will:
-Characterise inflammasomes in CNS lesions
-Establish the role of inflammasomes in myelin repair
-Modulate inflammasome activity to enhance myelin repair
The project is feasible to be delivered within 3 years; the models are well established in the host lab and expertise is available in house with additional support from our collaborators worldwide.
Start Date: October 2022
Continue with Facebook
