Given the prevalence of cancer, it is of utmost importance to develop new strategies to treat it. One of the most ambitious approaches is the use of microrobots, self-propelled microscopic devices capable of propelling themselves and being guided towards tumours where they can then effectuate a therapeutic action. Magnetotactic bacteria (MTB) are non-pathogenic aquatic microorganisms that synthesize intracellular magnetite nanoparticles within organelles called magnetosomes, and are ideal candidates to serve as microrobots for cancer theranostics. Suitably, they are highly motile, have preference for low oxygen conditions such as the inside of tumours, and can be externally guided, detected, and actuated by magnetic fields thanks to their chain of magnetosomes. In this project I propose a new approach to boost the therapeutic abilities of MTB by genetically engineering MTB to express immunotherapy-mediators on the surface of magnetosomes, and to create a triggered-release mechanisms to deliver these magnetosomes within the tumour microenvironment. This strategy, yet to be exploited, is more sustainable and cost-effective than the chemical-based approaches proposed to date. Specifically, new generations of MTB will maintain the genetic modifications without further need of surface modification or therapeutic loading steps. The perfomance and effectiveness of genetically modified MTB to swim towards and release the immunotherapy-mediating magnetosomes will be tested in vitro in 3D cancer cell models placed within microfluidic devices to mimic tumours and surrounding vasculature. DroneMTB is a highly interdisciplinary project that combines methods from materials science, microbiology, genetic engineering, biochemistry, microfluidics, microscopy, and cell biology. After carrying out the project I will have acquired necessary skills to become an independent scientist and to lead research projects in the field of biomaterials and biomedical applications.

Photoenzymes are rare biocatalysts that use the energy contained in photons to perform chemical reactions. To date, only one natural photocatalyst is known to have biotechnological applications; the Fatty Acid Photodecarboxylase (FAP), allowing the production of hydrocarbons from fatty acids. FAP belongs to a superfamily of enzymes called Glucose Methanol oxidoreductases (GMCox). Still, the FAP group is the only one known to perform photochemistry despite the high degree of structural similarity and presence of a photosensitive cofactor, Flavine Adenine Dinucleotide (FAD), in all GMCox. We reason that the GMCox family could have a latent photochemical function, and we would like to exploit it. Therefore, the objective of this project is to EXplore Photoinduced Enzyme pRomIscuity in the Glucose-Methanol-Choline oxidoreductase family to dEvelop New phoTocAtaLysts (EXPERIMENTAL). To this end, we will first test the photoinduced substrate promiscuity with different GMCox using an “accelerated serendipity” approach. In a second step, we will optimize the newly discovered photoenzymatic activity by directed evolution. Finally, the enzymatic mechanism will be characterized using different biophysics approaches, ranging from time-resolved spectroscopy to serial femtosecond crystallography. This project is inherently interdisciplinary, combining chemistry, biochemistry and biophysics to develop new photocatalysts for biotechnological purposes. For fundamental research these new photoenzymes will be an opportunity allowing the study of ultrafast processes that occur during catalysis and can only be observed with light-dependent enzymes such as electron and/or proton transfer, bond breaking ect. In fine, the goals of EXPERIMENTAL are to provide a better appreciation of the capabilities of enzymes and meet the demand for new and sustainable methods in organic synthesis by providing with the GMCox family a toolbox for the design of new light-driven reactions.

I propose to solve the Quantum Field Theory (QFT) describing the transition between plateaus of quantized Hall conductance in the Integer Quantum Hall Effect (IQHE). The existence of the plateaus and their topological origin are certainly well understood. In sharp contrast, the transition, which mixes the effects of disorder, magnetic field and possibly interactions, remains very mysterious. Numerical studies of lattice models are plagued by disorder. The QFT description involves physics at very strong coupling, and requires a non-perturbative solution before quantitative predictions can be made. Finding such a solution is very difficult because the QFT for the plateau transition is ‘non-unitary’ - it involves a non-Hermitian ‘Hamiltonian’. Non-unitary QFT is a challenging, almost unexplored topic, that must be first developed before the plateau transition can be addressed. I propose to carry out this task with a cross-disciplinary strategy that uses ideas and tools from conformal field theory, statistical mechanics, and mathematics. Key to this strategy is a new and powerful way of analyzing lattice regularizations of the QFTs by focussing on their algebraic properties directly on the lattice, with a mix of advanced representation theory and numerical techniques. The results - in particular, concerning conformal invariance and renormalization group flows in the non-unitary case - will then be used to solve the QFT models for the plateau transition in the IQHE and in other universality classes of 2D Anderson insulators. This will be a landmark step in our understanding of the localization/delocalization transition in two dimensions, and allow a long delayed comparison of theory with experiment. The results will, more generally, impact many other areas of physics where non-unitary QFT plays a central role - from disordered systems of statistical mechanics to the string theory side of the AdS/CFT duality, to the effective description of open quantum systems.