PhD in Parkinson's Disease: Ubiquitin Control of Neuronal Survival

Join Us!

We are looking for an enthusiastic PhD candidate for a project on the ubiquitin-dependent control of neuronal survival in Parkinson's disease (PD). Neurons in the substantia nigra pars compacta are selectively lost as PD progresses. Our work on the BCL2 protein family has identified MCL1 as a weak link in the survival of these neurons: it is a short-lived protein whose level is set by ubiquitin-dependent degradation and by its antagonist NOXA.

Do you want to find out which enzymes set that balance, and whether they can be used to keep dopamine neurons alive? Then this project is for you. We welcome applications from candidates with diverse backgrounds, experiences and perspectives. If you recognise yourself in the role but do not meet every listed preference, we encourage you to apply.

You will identify the E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) that control MCL1 and NOXA turnover in dopaminergic neurons, and determine what happens to neuronal survival when you manipulate them. The backbone of the project is interaction proteomics: you will perform (co-) immunoprecipitations from neuronal cell models and brain tissue followed by quantitative LC-MS/MS, and you will run that workflow from end to end – from sample preparation to data analysis and interpretation.

Candidate regulators are then validated biochemically, in cellular and in vivo models of PD, and finally in human post-mortem midbrain tissue, so that you can connect a molecular mechanism to the disease itself. You will work in a group that combines molecular neuroscience with proteomics and neuropathology, and you will have the room to shape the direction of your own project.

• complete and defend a PhD thesis within the official appointment duration of four years;
• contribute to the design of experiments, perform them, and analyse and interpret the results, with a focus on (co-)immunoprecipitation and quantitative mass spectrometry;
• perform in vivo and ex vivo rodent experiments within the scope of your animal licence and the approved project licence;
• keep accurate records by thoroughly documenting and organising your work;
• take a leading role in writing manuscripts and present your results at (inter) national scientific meetings;
• participate in the Faculty of Science PhD training programme;
• assist in teaching and co-supervise junior scientists (technicians, BSc/MSc students).

You enjoy hands-on experimental work, and you keep going when an experiment fails: you look for the reason rather than repeating it unchanged. You plan, so that long workflows such as a proteomics experiment are prepared well before the instrument time starts. You are precise in documenting what you do. You discuss your data critically in lab meetings, you ask for help when you need it, and you are a nice colleague in an interdisciplinary team of scientists.

• MSc in molecular biology, biochemistry, neurobiology or a related field;
• hands-on experience with mammalian cell culture, western blotting and (co-) immunoprecipitation;
• experience with the complete mass spectrometry workflow, from sample preparation and digestion through LC-MS/MS acquisition to data analysis and interpretation;
• a laboratory animal science certification (Article 9, rat/mouse) that is valid in the Netherlands at the start of the appointment;
• good knowledge of signal transduction and neuronal cell biology;
• good project and time management skills, enabling you to meet the project's deadlines for analyses, reports and other deliverables;
• good analytical, writing and presenting skills;
• fluency in English, both written and spoken, and the willingness to learn Dutch (in case you are not a…