PhD Studentship – Design, synthesis and Evaluation of Novel Small Molecule Modulators of Cell Signalling in Cancer

Unregulated cell signalling results in uncontrolled cell proliferation, and constitutes a hallmark of cancer. In this context, small molecule modulators of cell signalling continue to play a preponderant part in anticancer drug discovery. The Baud group group focuses on several important signalling pathways playing key roles in cancer progression, including the p53 and Wnt signalling pathways. These pathways play a pivotal role in normal organismal development. However, misregulation of their activity is a hallmark of several cancers, including colorectal cancer (CRC), one of the deadliest cancers worldwide. We aim to develop novel classes of small molecule modulators of these pathways, as proof-of-principle lead compounds towards first-in-class therapeutics against cancer.

The successful candidate will join a young and dynamic group at the School of Chemistry in Southampton to work on a challenging project at the interface of chemistry and biology. He/she will benefit from the outstanding facilities and vibrant environment provided by the School of Chemistry. The primary objective of the PhD candidate will be to develop a high profile drug discovery project aimed at identifying new anticancer small molecules targeting and modulating the biological activity of key misregulated proteins of these pathways. This will involve the molecular design, chemical synthesis and biophysical/biological evaluation of the synthesised small molecules. This medicinal chemistry project will be supervised by Dr. Matthias Baud at the School of Chemistry, supported by a strong network of collaborators in cell and structural biology.

Solid knowledge and experimental skills in synthetic organic chemistry will be helpful, as this will constitute the central part of this project. However, the multidisciplinary nature of this project will give the opportunity to the student to acquire knowledge and skills in other relevant disciplines both in our group and with our collaborators. Those include biophysical techniques (e.g. DSF, NMR, ITC, FP, SPR, MST), biochemistry (e.g. protein expression/purification), computational approaches (e.g. docking), cell biology (e.g. cytotoxicity assays, Western-blots) and structural techniques (e.g. X-ray crystallography).