Systems Biology of Prion Diseases

The researchers of the MRD Project PrionX are investigating the biomedical and cellular networks involved in the pathogenesis of prion diseases in order to find targets for treatment. The ultimate goal of the project is to translate this novel knowledge into the identification of new diagnostics and therapies for clinical application in related diseases such as Parkinson’s or Alzheimer’s.

Prion diseases such as bovine spongiform encephalopathy (BSE) are caused by the misfolding and ordered aggregation of proteins. They share this pathogenetic principle with Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, and a growing list of diseases of the nervous system and other organs. Because these diseases primarily affect the elderly, and due to an ever-increasing life expectancy, their prevalence is steadily rising. To date, no disease-modifying therapies exist. This bleak situation is compounded by a lack of validated therapeutic targets, which stems from an incomplete understanding of the biochemical and cellular networks involved in pathogenesis. 

The interdisciplinary PrionX research team therefore proposes to address the latter issue by exploiting the latest progress in genome editing (CRISPR) and microscale liquid handling (e.g. acoustic dispensing, microfluidics and ultra-high-density microplates). These technologies enable high-throughput, genome-wide perturbations of any cellular function for which an assay can be developed. 

Gaining insight into other diseases

Prion diseases will be the test bed for this project, as they offer the most robust cellular and animal models, and because their formal modeling has already undergone stringent validation. While certain pathways of degeneration will undoubtedly be specific to prion infections, the researchers expect many targets to be applicable to a variety of protein aggregation diseases, including Alzheimer’s and Parkinson’s disease. This way, the scientists involved in the MRD Project PrionX hope not only to gain new perspectives in prion biology, but also to yield knowledge applicable to these more common diseases. 

Updated June 2015