Open Positions
Group size and composition
The research group consists of about 8-10 PhD students, 5-6 postdocs, and 1 senior research associate. About half of the group
members work on computational projects while the remaining half do research in the experimental laboratory (protein production, biochemical and biophysical assays to measure binding, protein crystallography, and cryo-electron microscopy). The background of the
group members ranges from Master in Mathematics to Master in Cellular Biology.
Most alumni work in industry or academia.
For an academic career, the Caflisch group offers substantially higher chances than the average:
10 former PhD students (10 of 40, i.e., 25% ) were offered a position as junior group-leader or professor;
9 former postdoctoral fellows (9 of 27, i.e., 33% ) are currently employed as professors or independent group leader.
Master projects in simulation studies of RNA methylation
RNA methylation plays a fundamental role in the cell, and its deregulation is linked to cancer and other pathologies. We aim at shedding light on the atomic details of RNA methylation by molecular dynamics simulations (unbiased and enhanced sampling protocols) and data-driven, unsupervised analysis of the trajectories (see as an example Cocina et al., JCTC. 2020). Simulation results will be used to guide experimental activities (mutagenesis, protein crystallography, ligand design, etc) in our own research group. Note that we have already determined by X-ray crystallography more than 100 structures of m6A-RNA readers and the m6A-RNA methylase METTL3 in complex with small-molecule ligands.
Please submit a concise letter of motivation, CV, and the names of one or two professional references to Prof. A. Caflisch: caflisch[at]bioc.uzh.ch
The full application should consist of a single pdf file with all documents.
Postdoc positions in experimental biochemistry/biophysics
We currently have openings for the biochemical validation and structural characterization (by protein X-ray crystallography and cryo-EM) of our modulators of the m6A-RNA machinery Dolbois et al., J. Med. Chem. 2021.
Please submit a letter of motivation, CV, and the names of one or two (for postdocs) professional references to Prof. A. Caflisch: caflisch[at]bioc.uzh.ch
The full application should consist of a single pdf file with all documents.
Master thesis in the cellular characterization of targeted protein degraders
PROteolysis TARgeting Chimeras (PROTACs) induce the degradation of a protein of interest (POI) by simultaneously binding to the POI and an E3 ligase, leading to POI ubiquitination and degradation by the proteasome. Compared to small molecule inhibitors PROTACs have a number of advantages, including catalytic activity and the ability to target all protein functions simultaneously.
We are currently developing PROTACs targeting large multi-domain proteins whose dysregulation is implicated in a number of cancers, and have a promising lead compound to use as the basis of a further medicinal chemistry optimization campaign. Now, we are seeking an enthusiastic and motivated student to characterize the activity of these new compounds. The project will encompass a wide range of assays performed in mammalian cell lines, such as Western blotting to measure POI degradation, CESTA based analysis of POI binding, and cell viability assays to measure the anti-cancer effect.
Please send your application to i [dot] corbeski [at] bioc [dot] uzh [dot] ch. The start date is flexible.
Master thesis in the biochemical characterization of epitranscriptomic protein ligands
Description
Epitranscriptomics gathers all RNA modifications, which do not alter the nucleotide sequence. Among these modifications, several of them are involved in gene expression and play a key role in diseases such as cancer. m6A is the most prevalent RNA modification (over 160 reported so far) and became the focus of extensive research in the past years.
Currently, the role of m6A in biological processes and particularly in diseases remain elusive. Therefore, the Caflisch group identified several hits of small molecules binding to m6A-interacting proteins. Using computer-based methods, the development of these small molecules is expected to help in unraveling the role of the proteins they bind to. One of these hits has been successfully optimized to a low nanomolar inhibitor with favorable ADMET properties. However, there are several other hits waiting for characterization by biochemical assays, protein X-ray crystallography and/ or cryo-electron microscopy.
Qualifications
We seek an enthusiastic biochemistry student who enjoys the challenges of a multidisciplinary research project.
Starting date
flexible
Application
Please write to caflisch[at]bioc.uzh.ch
Prof. Amedeo Caflisch, Dept. of Biochemistry
Master theses in experimental biochemistry/biophysics
We currently have openings for master thesis work in the experimental part of the lab. You can find the details by following this link:
UZH official announcement
General information for PhD and postdoc positions
Applications to join our group are ALWAYS welcome from outstanding and enthusiastic Ph.D. and postdoctoral candidates. We offer a stimulating research environment at a highly ranked department within a university of excellent international standing. The quality of life in Zurich and in Switzerland in general is outstanding and well-documented by popular rankings.
There are frequently open positions in the laboratory and the best is to inquire. All our research projects are aimed at studying biological macromolecular systems. Current focus areas are situated in pathogenic protein aggregation and cancer therapeutics with a focus on epitranscriptomics (m6A-RNA) and epigenetics (bromodomains). Various projects have a strong component of methodology development while others require the application of existing approaches. Possible subjects include using molecular dynamics simulations to understand peptide aggregation and peptide-protein binding, the characterization of small molecule binding to macromolecules by simulations and experiments, the development of new ligands for therapeutically relevant targets by docking or de novo ligand design, and the development of new methods and models for classical biomolecular simulations. Applicants should preferably hold a Masters or Ph.D. degree in physics, mathematics, biophysics, chemistry, or biochemistry. We also perform experiments, specifically protein expression and purification, crystallography and a number of in vitro binding and functional assays such as time-resolved FRET and isothermal titration calorimetry. For computational applicants in particular, programming skills and a familiarity with the Linux operating system are highly advantageous. Individuals interested in applying for a PhD or postdoc position should submit a letter of application, resume, and the names of three professional references to Prof. A. Caflisch: caflisch[at]bioc.uzh.ch
The full application should consist of a single pdf file with all documents.
Please refer to the contact page for how to reach us or contact us by phone or postal mail.