January 8 - February 2, 2018.
Successful completion of 3120321PPY (How To Write A Research Proposal) is strongly recommended.
Student is assumed to be familiar with knowledge described in: Human Molecular Genetics (Strachan & Read): Chapters 4, 13, 14, 15, 16, 20, 21.
This four-week course will take you through the successive steps in the identification and characterization of the gene defect(s) in various monogenic and multifactorial diseases, with a focus on neurogenetic diseases.
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 (neuro)genetic disease, modern (genome-wide) gene identification strategies (Next Generation Sequencing), genome editing (CRISPR/Cas), functional assays, bioinformatics, model systems and therapeutic strategies will be 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. The experience gained will be used to design research proposals to be presented at the end of the week in a mini-symposium.
This course will particularly work on:
Defining a research question, writing a research proposal, choosing appropriate techniques
Collaborating with peers, commitment, motivation and drive, digesting other people’s opinions
has an overall understanding of the theoretical and practical features of family studies in (genetic) diseases
has an overview and knowledge of strategies to identify genes
has an overview and knowledge of functional assays and models for the development of treatment and prevention strategies of genetic diseases
can convey this knowledge and views to the other students
can implement this knowledge in the design of a written research proposal and an oral presentation about a chosen subject.
Mode of Instruction
Student behaviour (motivation, independency, oral reporting, participation in discussion)
The research proposal
The student’s oral presentation of his assignment during a plenary session with all course participants
This course will be given in parallel with the course: ‘Translational Neurogenetics’. A substantial number of lectures will be given for the combined group.