PhD position in Chemical Biology
Vor 6 Tagen
Bioactive peptide natural products are interesting leads for the development of pharmaceuticals as they (1) cover a huge chemical space due to their modular structure and (2) are, by their sheer size, able to cover a sufficient surface area on a protein to efficiently interfere with protein-protein interactions. In addition, these peptides often carry modifications of their amino acid side chains or their backbone that improve their pharmacokinetics e.g. provide passive membrane permeability to make them orally available and/or resistance to proteases to increase their retention time in the body.
Project backgroundIn the course of our basic research on fungal peptide natural products, we discovered that omphalotin A, a ribosomally synthesized dodecapeptide macrocycle carrying multiple backbone N-methylations and displaying toxicity towards the root-knot nematode Meloidogyne incognita, also has immunomodulatory activity. This activity is reminiscent of cyclosporin A, a structurally related fungal peptide natural product, that was discovered as antifungal in the late 1970s and has been employed as blockbuster immunosuppressant in organ transplantations. The immunosuppressive activity of cyclosporin A is based on its passive membrane permeability and its binding to the cytoplasmic prolyl-cis/trans-isomerase cyclophilin and the protein phosphatase calcineurin. Based on the immunomodulatory activity of omphalotin A and its structural similarity to cyclosporin A, we hypothesize that omphalotin A targets a different, yet-to-be-identified intracellular protein of immune cells to exert its function.
We propose to identify, in a 4-year PhD project, the target protein of omphalotin A in immune cells using two different proteomics approaches. The results of the experiments will provide insight into the mode of action of an immunomodulatory fungal peptide natural product. This insight may potentially contribute to the development of a novel immunomodulatory drug, based on the omphalotin A scaffold or its target.
ProfileYou are able to start on 1. May 2025, are an EU- or Swiss citizen with an MSc in Molecular Biology/Chemical Biology/Biological Chemistry and have a strong interest in the dissection of the mode of action of bioactive compounds at the molecular, cellular and organismal level. Experience in biotechnology, biochemistry and proteomics is desirable but not necessary.
WorkplaceWe offerWe offer guaranteed funding for 4 years, an excellent research infrastructure and a dynamic and international working atmosphere. You will be a member of the PhD program 'Microbiology and Immunology' of the Life Science Zürich Graduate School with its support and networking program.
In line with our values, ETH Zurich encourages an inclusive culture. We promote equality of opportunity, value diversity and nurture a working and learning environment in which the rights and dignity of all our staff and students are respected. Visit our Equal Opportunities and Diversity website to find out how we ensure a fair and open environment that allows everyone to grow and flourish.
Curious? So are we.We look forward to receiving your online application with the following documents:
- Letter of motivation
- Transcript of records
- Reference letters or contacts
Please note that we exclusively accept applications submitted through our online application portal. Applications via email or postal services will not be considered.
Further information about the Institute of Microbiology and Immunology and our research group can be found on our website and The Künzler Lab - Defense Mechanisms of Fungi, respectively. Questions regarding the position should be directed to Prof. Markus Künzler, Tel +41 44 6324925 or email mkuenzle@ethz.ch (no applications).
ETH Zurich is one of the world’s leading universities specializing 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.
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