Open Positions

Group size and composition

The research group consists of about 8-10 PhD students, 5-6 postdocs, and 3 senior research associates. Nearly two thirds of the group
members work on computational projects while about six to eight members do research in the experimental laboratory (protein production, biochemical and biophysical assays to measure binding, protein crystallography). The background of the
group members ranges from Master in Mathematics to Master in Cellular Biology.


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


Master thesis in the design and synthesis 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 an enthusiastic organic synthesis student to start a medicinal chemistry hit-to-lead campaign. The 30 crystal structures of the m6A writer enzyme complexes solved in-house will be used for protein
structure-based hit optimization.
In this project, you will combine retrosynthesis of one of the hit molecules, design of modifications through 3D software visualization of the protein-hit complex and synthesis of the planned derivatives. The aim is to obtain potency improvement while, as far as possible, respecting ADMET properties to achieve a viable lead molecule. The different synthesized compounds will be evaluated in biochemical/biophysical assays and, if possible and necessary, in cell-based experiments.

Qualifications

We seek an enthusiastic chemistry student who enjoys the challenges of organic synthesis and is interested in getting to know structure-based hit-to-lead optimization.

Starting date

July 2021 or later

Application

Please contact directly Frantisek Zalesak (f [dot] zalesak01 [at] gmail [dot] com). The work will be carried out directly in the Caflisch group.

Prof. Amedeo Caflisch

Director


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.