RAS proteins are natively involved in cell growth and signalling, yet when mutated they are the most common cancer-causing proteins present in 19% of 3.4 million new cancer cases yearly. Due to a lack of druggable pockets, RAS proteins are notoriously intractable to treat, illustrating the need for new approaches to target RAS signalling in cancer. The complex RAS signalling pathway involves various post-translational modifications (PTMs), with all oncogenic RAS proteins featuring lipid PTMs which are crucial for membrane association and activity. The lipid PTM S-acylation is attached at specific sites during signalling and dictates RAS localisation in multiple cancer types, presenting a unique opportunity to target RAS signalling in cancer. However, the reversible nature of S-acylation, wherein the lipid is rapidly installed and removed, makes it an extremely challenging PTM to study. Herein I aim to develop and apply the first light-responsive chemical probes to investigate dynamic reversible RAS S-acylation. Photoswitchable probes offer a unique tool for spatiotemporal control, an approach never used before to study S-acylation. This innovative method will shed light on the role of dynamic S-acylation of oncogenic RAS, leading to a better understanding of RAS lipidation dynamics and paving the way towards new cancer therapeutics.

Improved drag modelling for safer satellite operations The drastic increase in the number of space objects in the altitude region of 400 – 600 km impacts already now satellite operations as collision warnings occur much more frequently. In the future, we will need improved orbit prediction capabilities to enable safe satellite operations with fewer interruptions due to potential collisions. To reduce the present uncertainty of orbit predictions, we aim to improve the drag coefficient modelling. The benefit will be a more reliable risk assessment of potential collisions, which will lead to fewer false alarms.