Mass cytometry nanotools for intracellular target engagement. Towards precision medicine.

Cancer is the second highest cause of death in Europe and one of the biggest challenges facing humanity. The discovery of multi-kinase inhibitors has emerged as a strong alternative treatment for many cancers.

However, the appearance of severe side effects due to their intrinsic target promiscuity limits the dosage and efficiency of these treatments. Therefore the characterisation of this promiscuity is crucial to develop selective and safe treatments. We propose a versatile and efficient approach to detect the binding of a given drug to target proteins.

Combining intracellular target engagement devices based on nanotechnology with the state-of-the-art mass cytometry techniques, this approach will allow one-step target engagement profiling, and thus will streamline the discovery of the mode-of-action of a given drug.

Furthermore, the development of an intracellular barcoding system in combination with the multiplexing capacities of mass cytometry will allow for the combination of multiple cell types in one single experiment, further accelerating the target deconvolution process.

This research will greatly contribute to the development of a straightforward method to detect the most expressed targets in patient biopsies, and to select the best therapy for a given patient.

This fellowship will consolidate me as an independent researcher, providing me with the opportunity for many cross-disciplinary collaborations, and to establish myself as an expert in the field of precision medicine.