Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder caused by mutations in the DMD gene. Besides the known effects on striated muscle, it has cognitive and neurological impact manifested as lower IQ, epilepsy, autism, and hyperactivity disorder. Preliminary studies in our lab using gene edition and DMD patient’s iPSC lines show that dystrophin reduction leads to dysregulated calcium handling, altered presynaptic protein distribution and impaired neuronal connectivity. To understand the causes of presynaptic changes, the goal of this thesis is to analyze the axonal transport of synaptic vesicles and synaptic components distribution. To achieve this aim, the student will learn and perform techniques such as human iPSC culture, neuronal differentiation, immunofluorescence, live-imaging microscopy, image analysis, and basics of statistical analysis and experimental design. Furthermore, the student will learn the underlying basis and current knowledge on DMD, by conducting bibliographic research and also interpretation of scientific results. Last but not least, the student will gain experience in scientific work within an international team.

Goals:

1. Conduct a state-of-the-art review of Duchenne Muscular Dystrophy, with a particular focus on its effects on the nervous system and the relevance of the present thesis within that context.
2. Learn to work in a research laboratory environment and essential techniques such as cell culture, human iPSC culture and differentiation, neuronal differentiation, immunostainings and transfection.
3. Perform and master confocal microscopy and live-imaging.
4. Learn experimental design and basic statistical analysis.
5. Develop critical thinking and learn to interpret experimental results.
6. Gain experience working in a research group, collaborating with peers, and developing a proactive attitude towards achieving goals.