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.

This project project combines fundamental and applied research, and experiments and modelling in a unique way: from fundamental material-activity relations and insights into the reaction pathways during DAC with potassium-carbonate-based sorbents, over kinetic models, to heat and mass transport assessment and material shaping at the application scale. By understanding all these factors we aim to develop, together with our industrial partner Shell, new robust sorbent materials which can capture CO2 from air.

Biomineralization is a marvel of natural ingenuity that enables forming hard biological tissues, such as bone, but is also implicated in disease, such as soft tissue calcification. Achieving engineering control over mineralization using environmental cues could have far-reaching implications in regenerative medicine, e.g. to engineer complex mineralized tissue interfaces. However, it remains largely unclear how spatiotemporal mineralization is controlled in 3D evolving tissues, and how this is affected by environmental cues. In particular, the role of mesoscale geometrical cues, which have recently attracted great interest due to their ability to controllably steer cell- and tissue-level response, on mineralization remains elusive. Therefore, I will study bone tissue mineralization in dynamic, mesoscale, mechano-geometric environments by combining rational design strategies, high-resolution microfabrication, novel in vitro culture platforms, and state-of-the-art interface characterization techniques, such as quantitative Raman imaging and analytical electron microscopy. This interdisciplinary approach will provide novel insights on the mineral formation in geometrically constrained tissues, which will subsequently be leveraged to design mesoscale-structured surfaces that enable tunable mineralization control, including the formation of spatial mineralization gradients. As such, this project will advance fundamental understanding of the mechanobiology of biomineralization, and will push the frontiers of instructive biomaterial design for tissue engineering.

Modern computers can perform multiple computations simultaneously. Unfortunately, the coordination needed is very hard to program and test. In this project, I developed new techniques to make it simpler. Using mathematics as a solid foundation, I designed and implemented a new programming language and a new testing tool specifically tailored to coordination in software. A key contribution is that these new techniques support a significantly larger variety of coordination patterns than previous ones.

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.