The project aims to discover how angiogenesis (the growth of blood vessels) and the neurovascular unit’s perivascular cells are regulated during brain development, in brain tumours, and brain vascular malformations.
|Scholarship Sponsor||ETH Zurich|
|Scholarships level||PhD Position|
|Award Amount||Not Specified|
|Fellowship Period||Four years|
|Study area||Life Sciences Health|
|Opening date||February 26, 2021|
The research groups «CNS angiogenesis and neurovascular link» within the Neuroscience Center Zurich (University Zurich, University Hospital Zurich, and ETH Zurich), the «Laboratory for Exercise and Health» within the Department of Health Sciences and Technology (ETH Zurich), and the Functional Genomics Center Zurich of University Zurich and ETH Zurich, are seeking a PhD student in brain vascular biology.
Glioblastoma is amongst the most deadly human cancers, with a mean survival of only around 15 months. A typical feature of these tumours is their high grade of vascularization, which is established by angiogenesis. However, therapeutic approaches targeting angiogenesis in glioblastoma showed only poor outcome so far. The main reason is that the cellular and molecular mechanisms regulating angiogenesis within brain tumours are very complex and remain poorly understood. Brain arteriovenous malformations are morphologically abnormal connections between arteries and veins in the brain vasculature.
They lack an intervening capillary bed allowing high-pressure arterial blood flow from feeding arteries to shunt directly into the venous outflow system. The rupture of arterio-venous malformations is associated with significant morbidity and mortality. Aberrant angiogenesis is a key pathophysiological feature of arteriovenous brain malformations, and targeting angiogenesis has excellent therapeutic potential. The underlying cellular and molecular mechanisms regulating angiogenesis within brain arteriovenous malformations are highly complex but very poorly understood.
For both angiogenesis-dependent CNS pathologies, in addition to classical endothelial signalling pathways such as the Vascular Endothelial Growth Factor (VEGF) – VEGF Receptor (VEGFR) axis, new molecular pathways and thus therapeutic targets arise from the blood vessel microenvironment, also called the perivascular niche or neurovascular unit. In the healthy adult brain, blood vessels are mostly quiescent, with only < 0.5% of endothelial cells increasing. Importantly, in many angiogenesis-dependent brain pathologies such as brain tumours or brain vascular malformations, blood vessel growth is reactivated during disease initiation or progression, at least in part by up-regulating signalling pathways that are important for developmental brain angiogenesis and for recruitment of perivascular cells of the neurovascular unit.
In that regard, using unbiased system biology approaches and bioinformatic analyses of the above-mentioned human pathologies, novel and yet completely unknown angiogenic signalling pathways will be identified. Moreover, the novel and exciting concepts of a neurovascular link (common regulation of blood vessel- and neuronal growth) and endothelial metabolism will be explored.
The overarching aim of our groups’ collaborative efforts is to understand how angiogenesis and the neurovascular unit/perivascular niche are regulated in brain development, brain tumours, and brain vascular malformations.
We offer to work on highly original and translational projects regarding angiogenesis and the neurovascular unit/perivascular niche in brain development and brain tumours. The aim is to significantly improve the understanding and therapeutic modulation of the cellular and molecular mechanisms that govern angiogenesis and the neurovascular unit/perivascular niche during brain development, in brain tumours, and brain vascular malformations.
Our young and interdisciplinary team tackles these questions using a highly interdisciplinary and translational approach, including the combination of various in vivo and in vitro techniques and the variety and comparison of mouse and human tissues and cells.
Successful candidates will work under the direct supervision of Dr Thomas Wälchli in close collaboration with other PhD-students and postdoctoral fellows in the research groups.
The position is to be filled immediately, for three to four years. Conditions, according to the Swiss National Science Foundation.
The applications are open now
To investigate the above-described projects, the candidate will use a variety of in vivo mouse models and a broad spectrum of in vitro molecular biology, cell biology, and biochemical assays using the mouse and human endothelial and perivascular cells. A central component of the project will be the evaluation and interpretation of large-scale molecular data using the latest bioinformatics tools and strategies. Therefore, excellent training in biology and an MSc in neuroscience, biochemistry or molecular biology with experience in and enthusiasm for molecular- and cell biology, biochemistry, and animal experiments are required. Existing knowledge of bioinformatics and biostatistics is considered a strong plus.
To tackle those, as mentioned earlier high risk-high potential projects, candidates should demonstrate overwhelming enthusiasm for neuroscience, vascular biology, and tumour biology. Moreover, the candidate should be highly motivated and display flexibility with regard to experimental (the combination of various in vivo and in vitro experiments of human and mouse tissues) and organizational (the candidate will work between the Toronto Western Hospital, University Health Network and the University of Toronto and the University Zurich, the University Hospital Zurich and ETH Zurich) issues.
Therefore, we feel that only very dedicated, motivated, and talented persons will be able to work on the above-described successfully, highly novel and translational projects with the potential to significantly enhance our current knowledge on brain-, brain tumour -, and brain vascular malformation biology. Finally, the candidate should have the ability and self-motivation to work both independently and as a team player and should demonstrate good communication skills (German is not required, English is mandatory).
We look forward to receiving your electronic application in one PDF. It should include a cover letter stating your motivation for this position, a comprehensive CV including (potential) publications, your academic record including copies of degree certificates, and two references (including names and contact details).