PhD Making Human iNSCs from People with Progressive MS (PwPMS)

Closing Date

5 Dec 2018

Address

Department of Clinical Neurosciences, University of Cambridge

Project Description

This project will involve the development of stably expandable, forward programmed neural stem cells (NSCs) from People with progressive MS (PwPMS). Somatic cells will be reprogrammed to stably expandable directly induced neural stem cells (iNSCs) and then differentiated and monitored for several markers of pluripotency/multipotency, checked for morphological, function and genomic stability as well as senescence over time period in vitro. This project will highlight potential issues of stability and suggest methods of mitigating these, should they arise. 

The long-term goal of this investigation will be to evaluate the safety of iNSCs for use in a first-in-men clinical trial, which is being organised at Cambridge. The final objective of this investigation is the determination of whether or not the therapeutic use of iNSCs in PwPMS can be taken forward into clinical trials. In vivo characterization and manipulation of succinate dependent injury in neuroinflammation (co-supervised with Luca Peruzzotti-Jametti) 

Despite the absence of clinically relevant immune-related attacks, a diffuse activation of the immune system is thought to be one of the major drivers of disease progression in MS. However, differently from relapsing remitting MS, in progressive MS the immune cells that mediate the damage are called mononuclear phagocytes. Mononuclear phagocytes are not harmful per se, but they become so because of a chronic change in the ways they consume and produce energy. Energy production in a cell (or metabolism) is important for its function. We found that mononuclear phagocytes undergo a “metabolic switch” that makes them chronically active and accumulate one specific metabolite called succinate. 

The goal of this approach is to understand how different types of mononuclear phagocytes accumulate succinate during neuroinflammation and to interfere with their metabolism so that they stop damaging the brain. Moreover, thanks to a wide set of biological samples obtained from MS patients, we aim at finding out if succinate (or other metabolites) can be used as a marker to predict disability in MS patients. 

Funding Notes

Funding deadline is 5th December 2018 for start in October 2019. When applying indicate on the application the funding options (GATES USA *deadline 10/10/18*, Gates Cambridge or other Cambridge Funders). Home/EU and International applications are all considered for funding. 
Further information can be found on our website here