Thesis subject
Understanding individual genetic variation underlying human diseases
Current health care increasingly focuses on personalised medicine and understanding the role of individual genetic differences in disease progression. The genetic model organism C. elegans encodes many genes similar to those in humans and is therefore a great model for understanding why individuals differ in disease susceptibility and progression. Our lab aims to unravel effects of genetic variations and identify key modifier genes of diseases including Parkinson’s disease and alcoholism.
In this fast-developing field you will work with genetically diverse C. elegans strains, including genetically modified strains carrying human genes. With high-throughput techniques such as RNA sequencing of complex genetic crosses, we determine which genetic variants are involved in disease tolerance and susceptibility. Once we suspect a gene has a certain function or effect, this can be confirmed by means of CRISPR/CAS9 mutations in C. elegans. Generating CRISPR/CAS9 mutations in C. elegans involves using several technologies, including cloning, PCR, performing crosses, microinjections and sequencing. Finally, we study tag disease causing genes to be tracked by (protein) measurement techniques such as fluorescent microscopy, ELISA and Western blot and use pharmacological intervention assays to determine functioning of potential medicines.
Overall, your work will contribute to understanding how individual genetic variation changes (human) disease pathways from a molecular to organism scale to improve human health.