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A high-throughput library approach for minimizing peptide off-targets


   Institute of Chemical Biology

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  Dr L Walport, Dr B Schumann  Applications accepted all year round  Funded PhD Project (UK Students Only)

About the Project

Supervisors:

Recent breakthroughs in oral peptide delivery have vastly extended the chemical space which is available to drug protein/protein interactions and other challenging targets. High throughput techniques such as mRNA display that allow screening of enormous libraries of DNA encoded peptides are perfectly suited to provide clinical candidates of this kind. However, in contrast to more standard small molecules, de novo peptides carry an increased risk of engaging off-targets, leading to less effective drugs and higher attrition rates during the drug discovery process. Consequently, innovative technologies to address these challenges are critically needed. In this project we will develop a streamlined mRNA-display-based approach to identify and subsequently minimize peptide off-targets using a photo-affinity labelling strategy. Complementary data from next generation DNA sequencing and mass spectrometry will enable sophisticated in silico optimization of hit peptide sequences. The project will involve learning and applying a diverse range of modern chemical biology approaches, from peptide chemistry to proteomics, and AI and in silico design to cell biology. This project is a collaboration with Novo Nordisk and would ideally suit a student with a strong chemistry or chemical biology background and an interest in working with industry. Previous knowledge of high throughput technologies including peptide synthesis and analysis would be an advantage.


Funding Notes

UK residents or EU settled/pre-settled status can apply.
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