You will be working as a PhD candidate on "mRNA trafficking and local translation at the synapse", at the department of Functional Genomics at the Vrije Universiteit Amsterdam (VU).
Project description:Neurons are highly polarized and interactive cells that require precise spatiotemporal regulation of their proteome for proper functioning. mRNA localization and local protein synthesis are crucial in this process and play key roles in the development and maintenance of neurons. Importantly, dysregulation of this process is increasingly implicated in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy and Alzheimer's disease.
However, how a neuron regulates the localization of mRNAs and its translation remains poorly understood. Moreover, we know very little about the function of mRNA localization and local protein synthesis at presynaptic nerve terminals. The main focus of our research group is to understand the molecular mechanisms and functional relevance of mRNA trafficking and local translation in neuronal subcellular compartments. In particular, we are interested in the role of the endoplasmic reticulum in regulating mRNA localization and local translation. In this project, the aim is to understand the molecular mechanisms behind axonal ER-based translation and its role in presynaptic function in health and disease.
In this project, you will use live-cell and super-resolution imaging to assess the dynamics of mRNA and organelles at high spatio-temporal resolution. In addition, you will have the opportunity to work with proximity labelling techniques (for both imaging and proteomics) to understand the molecular mechanism behind axonal ER-based translation.
The work will be carried out in rodent neurons in culture and human iPSC-derived neurons.
You will be part of international research networks and exploit a variety of techniques and analysis tools available. All the methodology, cell models, equipment, analysis software and viral vectors are available from the start of the project. You will be trained on site and in specialized courses on campus.
Your duties:As a PhD candidate your main tasks and responsibilities are:
- investigate the dynamics of the endoplasmic reticulum and mRNA/ribosomes, using live-cell and superresolution imaging in cultured rodent neurons and human iPSC-derived neurons
- perform proximity labelling techniques to visualize protein interactions and identify proteins involved in ER-based translation
- publishing analyses in peer-reviewed journals and provide progress reports to funding sources
- contributing to teaching activities (~10% of your time), including supervision of BSc and/or MSc students during internships
- presenting your work to the international research community