In the last decade, super-resolution microscopy techniques have emerged as powerful quantitative tools for biology. They have capabilities to visualize single molecules at the nanoscale opening the door to study biological processes at a level not accessible before. In the ERC StG NANOSTORM we showed the potential of these techniques providing new fundamental knowledge on the mechanism and design of new targeted therapies. However, some of the methods we developed have the potential to be translated into applied clinical diagnostic tools. In NANODIAGNOSTIC, we would offer a proof-of-concept of the application of super resolution microscopy and single-molecule imaging for cancer diagnostic, with a focus on patients stratification for immunotherapy. Novel advances in immunotherapies have brought the development of immune checkpoint inhibitors (ICI) that re-activate the immune system against the tumor. Despite the high success of these therapies there is one main challenge: they are only effective on a limited portion of patients and current diagnostic approaches are not capable of stratifying patient successfully. NANODIAGNOSTIC will translate advance optical methods from an academic setting to the clinic and holds a great potential to provide new diagnostic methods to improve the outcome of immunotherapy.

Living organisms have acquired new functionalities by uptake and integration of species to create symbiotic life-forms. This process of endosymbiosis has intrigued scientists over the years, albeit mostly from an evolution biology perspective. With the advance of chemical and synthetic biology, our ability to create molecular-life-like systems has increased tremendously, which enables us to build cell and organelle-like structures. However, these advances have not been taken to a level to study comprehensively if endosymbiosis can be applied to non-living systems or to integrate living with non-living matter. The aim of the research described in the ARTISYM proposal is to establish the field of artificial endosymbiosis. Two lines of research will be followed. First, we will incorporate artificial organelles in living cells to design hybrid cells with acquired functionality. This investigation is scientifically of great interest, as it will show us how to introduce novel compartmentalized pathways into living organisms. It also serves an important societal goal, as with these compartments dysfunctional cellular processes can be corrected. We will follow both a transient and a permanent approach. With the transient route biodegradable nanoreactors are introduced to supply living cells temporarily with novel function. Functionality is permanently introduced using genetic engineering to express protein-based nanoreactors in living cells, or via organelle transplantation of healthy mitochondria in diseased living cells. Secondly I aim to create artificial cells with the ability to perform endosymbiosis; the uptake and presence of artificial organelles in synthetic vesicles allows them to dynamically respond to their environment. Responses that are envisaged are shape changes, motility, and growth and division. Furthermore, the incorporation of natural organelles in liposomes provides biocatalytic cascades with the necessary cofactors to function in an artificial cell

This proposal is on modelling of 3 phase gas-solid-liquid multi-component flows with catalyst particles, which are frequently encountered in industrial applications, but have not been tackled fundamentally before due to their complexity. Dense multi-phase flows have been intensively researched because of their scientifically interesting transport phenomena and industrial applications. Considerable progress has been made for gas-solid and gas-liquid two-phase flows. However, catalytic multicomponent three-phase flows have received relatively little attention despite their importance for the production of clean synthetic fuels, base chemicals, and many other products. Multiphase transport phenomena in such systems are poorly understood due to their complexity. Therefore the design of processes is cumbersome. In addition, the process operation is often far from optimal in terms of energy and feedstock utilization. Therefore significant improvements are required to boost the efficiency of three-phase systems, which demands for a better understanding of the transport fundamentals and complex interplay with chemical reactions and availability of predictive tools. The main underlying problem is the wide range of length scales: suspended catalyst particles have a size of 100-200 μm, whereas the diameter of industrial reactors is 5-10 meters. To tackle this problem a multi-scale modeling strategy is required. At the finest scale detailed models take into account the interaction between the phases. These interactions are condensed in closure laws for mass, momentum and heat exchange that feed so-called Euler-Lagrange models, which can then be used to compute the flow structures on a much larger (industrial) scale. The key innovative aspect of this proposal is the integrated approach including incorporation of multi-component chemical transformations and the validation on basis of one-to-one comparison of the of the computational results with experiments.