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Inhibitors of cilia and Hedgehog signaling: from phenotype to mechanistic understanding


About This PhD Project

Project Description

The Hedgehog (Hh) signaling pathway is a major contributor to embryonic development, and tissue homeostasis and stem cell maintenance in children and adults. For its correct function it relies on the primary cilium, a microtubule-based organelle, that dynamically organizes a variety of pathway components. Dysregulation of Hh signaling and/or ciliogenesis contributes to a plethora of human diseases, ranging from developmental disorders to cancer. To enhance our understanding of ciliary signaling and enable its manipulation, there is a need for the development of small-molecule compounds with a defined mechanism-of-action and cellular target. In this project, a CRISPR-based genetic screening platform[1] is implemented for mechanism-of-action and target ID studies of inhibitors of the Hedgehog pathway and/or cilia.

The Hoogendoorn lab is a newly established chemical biology lab at the University of Geneva. We are interested in the development and application of chemical tools to biological problems, in particular cellular signaling mediated by the primary cilium. We use a highly interdisciplinary approach, combining organic chemistry, molecular and cell biology, and genetics to generate new tools and enhance our understanding of cellular signaling.

We are looking for a highly motivated Ph.D. student with a M.Sc. in Chemical Biology, Chemistry, Biology or a related field that is excited about an interdisciplinary research project. Good English communication skills (both written and oral) are essential. The successful candidate will join the Department of Organic Chemistry and the NCCR Chemical Biology at the University of Geneva.

Start date as soon as possible upon mutual agreement.

Applications should include your complete CV, a letter of motivation stating your research interests and any research experience related to the field or a relevant field of study, and contact details of 2/3 persons for references. For more information, please contact prof. Hoogendoorn by email:

References

[1] Breslow, D. K.; Hoogendoorn, S.; Kopp, A. R.; Morgens, D. W.; Vu, B. K.; Kennedy, M. C.; Han, K.; Li, A.; Hess, G. T.; Bassik, M. C.; et al. A CRISPR-Based Screen for Hedgehog Signaling Provides Insights into Ciliary Function and Ciliopathies. Nat. Genet. 2018, 50 (3), 460–471. https://doi.org/10.1038/s41588-018-0054-7.

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