Prof. Dr. Andreas Walter

The great strength of fluorescence microscopy (FM) at room temperature is its ability to study living cells. In cases where the dynamics are too fast and the sample needs to be immobilized for imaging (e.g., for super-resolution (SR) FM), chemical fixation is usually the method of choice. However, chemical fixation is associated with structural changes in the sample and can lead to artifacts in the microscopy images, which in turn can lead to misinterpretation of biological functions and mechanisms. Rapid freezing (vitrification) of the sample allows immobilization in a near-natural state. Structural preservation is particularly important for microscopy techniques that achieve very high resolution. Therefore, the main application of cryo-FM is in combination with cryo-electron microscopy (EM). Nevertheless, cryo-FM can also be combined with SR imaging and serve as an alternative to classical SR-FM in chemically fixed samples. In this project, we aim to develop a unique cryogenic SR-FM below the Abbe diffraction limit with structured illumination (SIM). The cryogenic SIM setup will visualize molecules with twice the lateral resolution compared to conventional FM and enable optical sections. This setup sets the stage for correlating FM with cryo-EM (in particular focused ion beam scanning electron microscopy) and addressing clinically relevant research questions. The correlation of microscopy techniques under cryogenic conditions is important because it directly images specific molecules in their original cellular context: While EM allows visualization of the subcellular architecture of a cell, molecular complexes within that cell can only be uniquely localized by FM.

This project will consolidate and extend a collaborative and innovative network promoting MultiModal Imaging and analysis across scales (MMI) from biological research to clinical diagnostics, and establish a global multimodal imaging association (COMULISglobe) to ensure long term sustainability. MMI integrates the best features of combined techniques and overcomes limitations faced when applying single modalities independently. MMI relies on the joint expertise from biologists, physicists, chemists, clinicians, and computer scientists, and depends on coordinated activities and knowledge transfer between technology developers and users. To achieve this inherently interdisciplinary goal, it is indispensable to establish a network of scientists across continents and disciplines, from academia and industry, including transnational research facilities (e.g. synchrotrons, Euro-BioImaging ERIC), to foster and market MMI as a versatile tool in biomedical research and diagnostics. We will capitalize on COMULIS, a European initiative (comulis.eu), and extend it globally and sustainably. The network will raise awareness of the manifold benefits of MMI, train researchers, and promote a scientific mindset enthusiastic about interdisciplinary imaging and analysis. The MMI network will help bridge the gap between biological and clinical imaging, identify, fund, and showcase novel multimodal pipelines, and develop, evaluate, and publish correlation software through dedicated networking activities, including conferences, training schools, open databases, and fellowships for lab exchanges, access to research infrastructures, and conference attendance. All outputs of the project will be open access.

www.comulis.eu

CLEXM is a Marie Sklodowska-Curie Doctoral Networks Action (MSCA-DN), funded by the European Union under Horizon Europe. The objective of MSCA-DN Project is to implement doctoral programmes by partnerships of organizations as well as to train highly skilled doctoral candidates, stimulate their creativity, enhance their innovation capacities and boost their employability in the long-term. Partner organizations include the Institut Pasteur in Paris, University College Dublin, and ALBA synchrotron in Barcelona. CLEXM addresses an urgent need for collaborations in the field of correlative multimodal imaging. It will gather and integrate information from complementary imaging modalities to create a more complete view of biomedical processes of disease and drug therapy research.

www.clexm.eu

Cancer treatment using radiation and chemotherapy also damages healthy cells. With a new approach to fighting tumors, the interdisciplinary joint project "NanoLYRIC" by Aalen University, the Karlsruhe Institute of Technology (KIT), and Göttingen University Medical Center (UMG) aims to kill cancer cells in a more targeted and efficient manner than before and reduce side effects on healthy tissue. To this end, Prof. C. Feldmann's research group at KIT is developing novel nanoparticles that are loaded with chemotherapeutic agents and contain gold as a heavy element. During radiation therapy, these nanoparticles absorb increased radiation in the tumor tissue and release the chemotherapeutic agents selectively and only in the tumor when exposed to radiation. This simultaneous combination of radiation and chemotherapy mediated by the nanoparticles enhances the effect of cancer therapy by selectively killing only the cancer cells and sparing healthy tissue.

This new nanoparticle-based therapy is being evaluated preclinically by Prof. F. Alves, Prof. C. Dullin, and Prof. S. Rieken at the UMG for its accumulation in the tumor and its effect. For the evaluation, Prof. A. Walter and Prof. C. Neusüß at Aalen University and the UMG are using cross-scale imaging techniques.

The aim is to reduce the side effects of therapy on healthy tissue and the body as a whole while improving therapeutic efficacy, thereby enhancing patients' quality of life and chances of survival.