Optimization of Bacterial Histidine-kinase Inhibitors


Novel antibacterial are urgently needed because of the growing problem of antibacterial resistance. Bacterial histidine kinases (HK) are promising targets for novel antibacterials (Velikova et al. 2013, Bem et al. 2015). We have previously identified promising HK inhibitors (patent application number P201431627) and our current goal is to discover and/ or design more potent and selective HK inhibitors with improved drug-like properties.

There are different thesis possibilities within this project with various objectives.

Techniques and procedures you can get acquainted with:

Some of the techniques and procedures you can learn include but are not limited to
-    Protein expression in E. coli and purification using chromatography and FPLC
-    Biochemical, microbiological and cellular assays for screening
-    Methods to study enzyme kinetics and inhibition 
-    Mutation/ resistance development experiments
-    Learn/use in silico methods for virtual screenings, molecular modelling, molecular docking and other applicable to computer-aided drug design.  
You will be also given the opportunity to propose and pursue your own ideas within the scope of the project (optional). 
Furthermore, if you are interested and depending on the progress, there is a possibility part of the thesis or a future thesis/ internship to be performed in collaborator’s laboratories with different expertise (e.g. Structural Biology/ X-ray crystallography; Enzyme kinetics; Infection models etc.).


For information contact Nadya Velikova ( , Host-Microbe Interactomics Group