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Student (m/w/d) for a Master Thesis in the Institute for Neuropathology, Zurich Switzerland
A Master thesis position is available with a flexible start date and duration, preferentially of > 6 months in the Institute of Neuropathology, led by Professor Adriano Aguzzi.
Keywords: Master thesis
Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Prion disease (PrD) are incurable and affect millions of people worldwide. A hallmark of neurodegeneration is the prion-like spread of protein aggregates such as a-beta and tau in AD, a-synuclein in PD and prion in PrD hinting at a common underlying mechanism. This mechanism was first described in prion diseases where the normal form of the prion protein (PrPC) gets misfolded into the infectious form (PrPSc), acting as a template for more PrPC to adopt a misfolded conformation and form toxic protein aggregates. These pathological aggregates can spread from cell to cell, leading to further propagation among neuronal cells and brain regions, and causing cellular vacuolation and neuronal death.
Using siRNA arrays, the Aguzzi lab has identified genetic modifiers of α-synuclein cell-to-cell transfer (Kara et al., Cell Rep, 2021), of PrP expression (Heinzer et al., PLoS Pathog, 2021) and of prion replication (Avar et al., EMBO J, 2022). In this effort, the lab has constructed >42’000 arrayed CRISPR deletion and activation gRNA plasmids organized in two libraries (Yin et al., bioRxiv, 2023), with which we are interrogating all protein-coding genes that modulate the formation, toxicity and spread of prions.
By taking advantage of these powerful screening resources, we have performed a CRISPR activation screen to find genetic modulators of prion replication in human cells and have generated a list of potential genetic candidates that either decrease or increase the cellular prion levels. The goal of the project is to validate the genetic hits derived from the screen and further elucidate the molecular mechanisms underlying prion replication.
Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Prion disease (PrD) are incurable and affect millions of people worldwide. A hallmark of neurodegeneration is the prion-like spread of protein aggregates such as a-beta and tau in AD, a-synuclein in PD and prion in PrD hinting at a common underlying mechanism. This mechanism was first described in prion diseases where the normal form of the prion protein (PrPC) gets misfolded into the infectious form (PrPSc), acting as a template for more PrPC to adopt a misfolded conformation and form toxic protein aggregates. These pathological aggregates can spread from cell to cell, leading to further propagation among neuronal cells and brain regions, and causing cellular vacuolation and neuronal death.
Using siRNA arrays, the Aguzzi lab has identified genetic modifiers of α-synuclein cell-to-cell transfer (Kara et al., Cell Rep, 2021), of PrP expression (Heinzer et al., PLoS Pathog, 2021) and of prion replication (Avar et al., EMBO J, 2022). In this effort, the lab has constructed >42’000 arrayed CRISPR deletion and activation gRNA plasmids organized in two libraries (Yin et al., bioRxiv, 2023), with which we are interrogating all protein-coding genes that modulate the formation, toxicity and spread of prions.
By taking advantage of these powerful screening resources, we have performed a CRISPR activation screen to find genetic modulators of prion replication in human cells and have generated a list of potential genetic candidates that either decrease or increase the cellular prion levels. The goal of the project is to validate the genetic hits derived from the screen and further elucidate the molecular mechanisms underlying prion replication.
You will gain experience in cell culture, CRISPR screens, flow cytometry, sorting, immunohistochemistry, qPCR, Western. The majority of the work will be performed in high biosafety lab (BSL2+ and BSL3). Part of the results will be featured in future scientific publications. Finally, you will have the chance to work in an interdisciplinary and multicultural research team.
A degree in biological/biomedical sciences and previous experience in basic molecular techniques and/or cell culture is required. The student should be highly motivated, eager to learn many new things and willing to take over responsibilities. The student will also be expected to demonstrate a good grasp of basic concepts of molecular biology and genetics in order to participate in the biological interpretation of the results and make suggestions for the next steps. Excellent oral/written communication skills in English are required.
You will gain experience in cell culture, CRISPR screens, flow cytometry, sorting, immunohistochemistry, qPCR, Western. The majority of the work will be performed in high biosafety lab (BSL2+ and BSL3). Part of the results will be featured in future scientific publications. Finally, you will have the chance to work in an interdisciplinary and multicultural research team.
A degree in biological/biomedical sciences and previous experience in basic molecular techniques and/or cell culture is required. The student should be highly motivated, eager to learn many new things and willing to take over responsibilities. The student will also be expected to demonstrate a good grasp of basic concepts of molecular biology and genetics in order to participate in the biological interpretation of the results and make suggestions for the next steps. Excellent oral/written communication skills in English are required.
To apply, submit a cover letter, CV and academic transcripts to evangelos.bouris@usz.ch. We are looking forward to your application!
To apply, submit a cover letter, CV and academic transcripts to evangelos.bouris@usz.ch. We are looking forward to your application!