PhD position: Proteomic Profiling Of Drug Target Interactions in Zürich

100%, Zurich, temporary

The research group of  at the Institute of Molecular Systems Biology (ETH Zurich) offers a PhD position to develop and apply mass spectrometric techniques for profiling drug target interactions. The Gstaiger group is embedded within the laboratory of Prof. Paola Picotti and has a strong interest in analyzing the behavior of dynamic protein networks to better understand and predict cell signaling in health and disease.

The research project is part of the European Innovative Medicines Initiative (IMI) funded project . EUbOPEN involves 22 partners from academia and industry and aims to create the largest and most deeply characterised collection of chemical modulators of protein function that is openly available.

Most drugs have significant side effects, which to a large extent are caused by binding to non target proteins or by changing target protein complexes. Changes in target protein complexes in turn can alter localization, stability or substrate specificities of target enzymes. Lack of throughput and analytical depth of classical biochemical approaches compromises our understanding on how drugs induce changes on a proteome wide scale. Recent advances in mass spectrometry based proteomics however opened new routes for global target engagement profiling. In this PhD project we aim to develop and apply proximity proteomics and structural proteomics techniques to study target engagement by a class of drugs that target E3 ubiquitin ligase components. Specifically we aim to develop mass spectrometric techniques to identify and better understand neosubstrate ubiquitination by E3 ligases in response to immunomodulatory imide drugs (IMiDs) which are used to treat myeloid blood cancer diseases in the clinic. We hope that these efforts will (i) help explain how known clinical side effects are caused by these drugs but also will (ii) help to rationalize the design of new compounds to reprogram substrate specificities of ubiquitin ligases for the degradation of other disease linked proteins.

We offer a highly collaborative and stimulating research environment at the IMSB including state of the art mass spectrometry instrumentation. This project is part of a European collaborative project (EUbOPEN) between universities and industry partners providing unique opportunities to build a strong collaborative research network.

Candidates for this project should have a strong background in chemistry and biochemistry, have a thrill for data analysis (R, Python) and like to think outside the box. Interested candidates should in addition be good team players and have excellent communication skills since we strongly promote an open and collaborative research culture to address our goals.

ETH Zurich is one of the world’s leading universities specialising in science and technology. We are renowned for our excellent education, cutting-edge fundamental research and direct transfer of new knowledge into society. Over 30,000 people from more than 120 countries find our university to be a place that promotes independent thinking and an environment that inspires excellence. Located in the heart of Europe, yet forging connections all over the world, we work together to develop solutions for the global challenges of today and tomorrow.