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The Center for Neurogenomics and Cognitive Research in Amsterdam participates in the Graduate School Neurosciences Amsterdam Rotterdam and is seeking applications for two PhD-students in (cellular) neuroscience (neurophysiology, life cell imaging, cell biology) for two projects.
Communication between neurons in the brain depends on the secretion of chemical messengers from synaptic and dense core vesicles and the trafficking of these vesicles to and within the synapse. Several genes involved in these processes are now firmly implicated in brain disorders like schizophrenia, autism, epilepsy and mental retardation. The aim of the projects is to unravel the mechanisms of vesicle trafficking and secretion in neurons, and to analyze how these processes are affected by disease.
Project 1 (COSYN1): Effect of genetic variation in human brain disorders on synaptic transmission.
Several exon variants and single gene CNVs are now firmly associated with schizophrenia, autism, mental retardation and epilepsy. We have previously identified synaptic gene networks where many such risk factors accumulate Using two reduced and highly standardized model systems, we aim to systematically analyze the synaptic effects of different exonic variants and single gene CMVs in a large European collaboration named COSYN. In this project, we will focus on presynaptic function. As model system we will exploit human iPS-cell derived neurons from patients and controls, sampled by others in the COSYN team and analyze synaptic transmission using patch clamp physiology. We will exploit modern gene-editing methodology to generate models for schizophrenia, autism, mental retardation and epilepsy, introducing mutations and gene deletions to study the synaptic function of disease-associated genes. Life cell imaging experiments will be used for independent analysis of synaptic functions. Together these studies yield roughly 50 functional parameters which together assist in predicting the synaptic consequences of genetic variation associated with schizophrenia.
Project 2 (ERC-DCV fusion): The mechanisms of trafficking & fusion of neuropeptide vesicles in health and disease.
Many of the modulatory signals that change our brain state (arousal, sleep, euphoria) are secreted from dense cored vesicles (DCVs) in neurons. Dysregulation of DCV trafficking and release is at the basis of many disorders, like neuropsychiatric disorders. The aim of this project is to unravel the mechanisms of DCV trafficking and secretion in neurons at the single vesicle level from the initial biogenesis at the Golgi to the final fusion at synapses. This project uses life cell imaging (2-photon imaging and confocal microscopy) in intact rodent tissue (brain slices, in vivo) and human iPSC-derived neurons, and genetically encoded reporters to detect DCV trafficking and fusion. We have previously established detection of DCV secretion in living neurons at the single vesicle level and characterized several molecular factors that regulate secretion of neuropeptides in chromaffin cells. In this project we will exploit these tools/methods to test whether these principles operate in neurons and how the secreted cargo affects network activity and behavior. Using two recently acquired/rebuilt microscopes, we are now able to witness the behavior of individual vesicles prior to secretion in normal and mutant neurons in intact tissue.
These projects are part of EU-funded projects on cellular trafficking (ERC Advanced DCV fusion, H2020 COSYN) and a national grant (ZonMw TOP Grants). The PhD-projects will be integrated in these larger project groups.
All projects use cultured rodent and human neurons, and modern genome editing to delete/modify candidate genes or introduce/correct disease-relevant variation. As main analysis tools, you will primarily use patch clamp electrophysiology and fluorescence imaging (project 1) or life cell imaging and cellular trafficking assays (project 2). All projects will test their main findings in more integrated models (brain slices and in vivo). You will be part of (inter-)national research networks and will be able to exploit a variety of other analysis methods available within the networks. All projects are based in Amsterdam and you will work primarily in Amsterdam with regular visits to the participating labs. The PhD-students will be trained on site and in specialized courses on campus.
We are looking for candidates that hold, or will soon hold, a master degree in (Medical) Biology, Biophysics or Physics, preferably with hands-on experience in (neuronal) cell culture and microscopy, and a strong motivation to pursue a career in science. Experience with cellular imaging and/or patch clamp physiology are an advantage.
Salary Scale OIO: 2279 tot 2919 euro gross when employed full-time (depending on qualifications and experience).
In addition to a good base salary, we offer, amongst others, an 8,3% end-of-year bonus and 8% holiday pay. For more information on our fringe benefits, please see our benefits http://www.werkenbijvumc.nl/vumc/arbeidsvoorwaarden/
For Dutch citizens it is mandatory to provide a VOG (Verklaring Omtrent Gedrag).
Please send cv and cover letter together as one PDF.
If you’re interested about this position, you can contact Prof. dr. Matthijs Verhage, via telephone number 020 598 6936. If you need more information about the application procedure, contact Evelien Hoozemans, corporate recruiter at 020 444 5635. You can apply till 28 February 2018 by using the apply button.
Acquisition based on this vacancy is not appreciated.