Neurological disorders have emerged as a significant global societal burden, exemplified by afflictions like Alzheimer's and Parkinson's, impacting over one billion individuals globally and surpassing the combined economic burden of cancer and diabetes. This has spurred a concerted global effort, with increased support for neuroscience research. These disorders often target deep brain regions and profoundly influence the structural connectivity of neuronal cells within functional circuits. Synapses, where neurons exchange information, exhibit plasticity, altering information transmission efficiency, shape, and position. Understanding the mechanisms underlying these structural changes, especially in neuronal circuits, remains limited in both healthy and affected individuals. The ERC PoC project STEDGate seeks to advance our understanding of neuronal connectivity and plasticity by developing STED-enabled holographic endo-nanoscopy for neuroscience. This ground-breaking technology promises atraumatic nanoscale in-vivo imaging of deep brain structures reaching depths up to 5 mm beneath the brain's surface. Collaborating with the start-up endeavour DeepEn, the team aims to facilitate the commercial transition of this technology. Making deep-tisue nanoscopy available globally will revolutionize our ability to monitor and understand neurological disorders and, ultimately, offer new avenues for intervention and treatment..

In most European countries, the diagnosis of cancer is achieved by examination of haematoxylin-eosin (HE) staining by an experienced pathologist. Nevertheless, several other diagnostic approaches exist (e.g., immunohistochemical staining) which are not applied routinely for all cases due to their technical complexity, duration, and cost. Therefore, an important unmet medical need for fast, non-invasive, and label-free immunohistochemical staining based on molecular imaging without laborious sample treatment exists. This demanding challenge will be tackled in STAIN-IT using a non-invasive label-free measurement technique called multimodal imaging (e.g., the combination of coherent anti-Stokes Raman scattering, second harmonic generation, and two-photon-excited fluorescence). The multimodal images will be analysed using deep learning approaches, such as convolution neural networks (CNNs). These CNNs are utilized to mimic immunohistochemical stainings. CNNs are neural networks that learn the feature representation of the data, which is optimally suited to model a specific immunohistochemical staining. In STAIN-IT, the staining models will be developed along with the methods to quantitatively understand the nonlinear behaviour of the CNNs. With the envisioned approximation approaches for CNNs, these models no longer act as ‘black box’ systems, and a quantification of tissue changes associated with the staining models can be achieved. For the very first time, STAIN-IT will develop a label-free, non-invasive, labour-inexpensive, and fast computational immunohistochemical staining, which can be easily implemented into clinical routine yielding increased diagnostic reliability and a better understanding of disease pathogenesis. A fast test of the antigen KI-67 in an intraoperative frozen section consultation situation or the use of Collagen IV as a quality control marker of tissue-engineered medicines are some of the exciting application possibilities of such staining model.

A dysfunction of cells lining the inner walls of blood vessels, i.e. the endothelium, is the primary cause of many lifestyle related diseases. According to the WHO, those diseases accounted for 60% of all deaths worldwide in 2005. Tailor-made diagnostic tools for early and reliable identification of endothelial dysfunction are urgently needed both in fundamental research and clinical routine, respectively. The Marie Skłodowska-Curie action LOGIC LAB objects to develop and characterize innovative molecular logic gates that can be applied as advanced diagnostic tools for parallel analyte sensing in live mammalian cells. Thereby, providing a unique method to discover endothelial dysfunction and the onset of diseases much easier and earlier than so far. LOGIC LAB creates a multi-faceted and multi-sectoral research environment for the next generation of scientists in order to establish a novel type of molecular logic sensors that reliably operate in biological media – a crucial requirement for their application i.e. as rapid and easy-to-handle tools for intracellular diagnostics. With excellent cross-disciplinary scientific and complementary training provided in the network, we aim to educate highly-skilled young scientists in the fields of chemistry, physics and biology, who will significantly strengthen the international research community in the domain of molecular logic sensing. Thus, in the long term, LOGIC LAB aims to finally bridge the gap between lab bench and biological or medical practice. It is this gap, that so far prevents a wide-ranging use of existing molecular logic gates e.g. for the diagnosis of lifestyle-associated diseases.