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Up Directory CCL 23.10.06 PhD position in structure-based design of RNA-ligands in Norway
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Date: Fri Oct 6 09:50:13 2023
Subject: 23.10.06 PhD position in structure-based design of RNA-ligands in Norway
The vast majority of targets for approved drugs are proteins. In recent years, 
it has been increasingly realized that also RNA molecules constitute promising targets.
However, compared to protein targets, RNA targets are vastly underexplored.
By targeting RNA, the functions of currently undruggable protein-mediated 
pathways and the non-coding transcriptome can be modulated and thus the 
size of the druggable genome can be increased substantially. A major 
obstacle in RNA-targeting drug discovery is the lack of knowledge on how to
obtain drug-like RNA ligands. The main goal of this project is therefore to
establish a blueprint on how to design drug-like, potent, selective, and functional
RNA ligands based on the 3D structure of the target and to advance our 
understanding of what drives potency and selectivity of RNA ligands on the 
molecular level. Focusing on RNA targets that contain druggable binding 
site will allow us to transfer methods that are at the forefront in 
structure-based design in the protein field to RNA. For that purpose, we 
have chosen two emerging targets for antibiotics, the FMN and 
TPP riboswitches (genetic switches in bacterial mRNA), as model systems. 
Hit compounds will be advanced through design-synthesis-test cycles and 
extensively characterized in terms of binding affinity and kinetics, 
functional activity, selectivity, and binding modes. This will deliver 
detailed knowledge about RNA-ligand interactions which is crucial to 
advance RNA-targeted drug discovery. In addition, the project will deliver 
advanced starting points for antibiotic drug discovery. We anticipate that 
this study will lead to a paradigm shift in the RNA field away from the 
currently rather unsuccessful one size fits all approach to a more 
target-centred approach where the nature of the binding site is taken into 

In this project, two PhD students, one postdoc and one researcher will 
tightly collaborate on compound design, synthesis and testing. More 
information about the project can be found here:

The main objectives for the advertised PhD position are

  -  to carry out structure-based design of RNA-ligands
  -  to establish computational methodology on how to harvest the 
     potential of large, chemically accessible combinatorial spaces for 
     the design of RNA ligands
For more information and instructions on how to apply, see here:
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