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

Supervisory Team:   Dr Matthias Baud

Project description

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 lab (www.baudlab.co.uk) 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 many aggressive and poorly treatable cancers. We develop novel classes of small molecule modulators of these pathways, as proof-of-principle lead compounds towards first-in-class therapeutics.

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 lead a high profile drug discovery project and identify preclinical anticancer small molecules targeting and modulating the biological activity of key disease driving proteins. 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 essential, as this will constitute the central part of the project, at least initially. 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/biochemical assays (e.g. DSF, NMR, ITC, FP, SPR, MST), biochemistry (e.g. protein expression/purification), computational approaches (e.g. molecular docking), cell biology (e.g. cytotoxicity assays, Western-blots) and structural techniques (e.g. X-ray crystallography). Knowledge of these complementary areas is desirable, but not essential.

This project is in collaboration with A* Singapore, and the candidate will also spend time there to pursue expert training in computational drug design with our collaborators.

If you wish to discuss any details of the project informally, please contact Matt Baud, Chemical Biology, Diagnostics and Therapeutics Research Group, Email: [Email Address Removed].

Entry Requirements

A very good undergraduate degree (at least a UK 2:1 honours degree, or its international equivalent), in organic chemistry or allied subjects/relevant discipline

Closing date: applications should be received no later than 15 March 2023 for standard admissions, but later applications may be considered depending on the funds remaining in place.

Funding: Due to funding restrictions this position is only open to UK applicants, Tuition Fees and a stipend of £17,668 tax-free per annum for up to 4 years.

How To Apply

Apply online: Search for a Postgraduate Programme of Study (soton.ac.uk). Select programme type (Research), 2023/24, Faculty of Physical Sciences and Engineering, next page select “PhD Chemistry (Full time)”. In Section 2 of the application form you should insert the name of the supervisor Matthias Baud

Applications should include:

Curriculum Vitae

Two reference letters

Degree Transcripts/Certificates to date

For further information please contact: [Email Address Removed]