Period: January 6 – January 24, 2014
Neurogenetic diseases form a major medical, personal and societal burden in the population. Many of the diseases show an early onset, while we see a steep increase in various neurodegenerative disorders in the ageing population. In Leiden, there are several strong clinical-molecular research groups working on episodic (e.g. migraine, stress/depression), neurodegenerative (e.g. Huntington, Parkinson, Alzheimer) and neuromuscular (e.g. Duchenne, FSHD) diseases. These collaborative networks provide unique opportunities for translational research “from bench to bedside – and back”. In this course, much emphasis is given to the functional consequences of the mutations in the DNA (i.e. genotype) – on the RNA, protein and metabolite level (i.e. phenotype). Thus, subsequent to gene and mutation identification, their functional consequences need to be studied in various in vitro and in vivo model systems. Our main emphasis will be on transgenic and (conditional) knock-out mouse models. These models are studied with cutting edge molecular, (electro)physiological, behavioural and imaging techniques. How knowledge of genetic and functional studies can lead to the identification of targets for the development of therapeutical strategies will be discussed.
The flow of the course is as follows:
In the first part of the course, a thorough theoretical overview of the various steps in gene discovery and functional characterization is given. Important issues such as collection and diagnosis of families and populations with a neurogenetic disease, modern (genome-wide) gene identification strategies, functional assays and model systems are discussed in lectures, demonstrations and self-study assignments.
In the second part of the course, students participate in ongoing disease-oriented projects to get a better insight in modern translational neurogenetics research. Specific emphasis is given to the complex neurobiological processes at the basis of the observed clinical phenotype in patients and mouse models. Finally, the experience gained will be used to design research proposals to be presented at the end of the week in a mini-symposium.