Multispectral Optoacoustic Tomography (MSOT) brings a revolution to bio-optical imaging. Being insensitive to photon scattering, MSOT dramatically improves upon conventional bio-optic barriers by enabling (1) three-dimensional high-resolution optical imaging deep inside tissues (several millimetres to centimetres), by (2) high-scalability, ranging from optical-resolution microscopy to acoustic-resolution optical mesoscopy and macroscopy and by (3) novel label-free anatomical, physiological and molecular contrast at the tissue and single-cell-level, based on spectrally-resolved optical absorption. MSOT, originally supported by an ERC Advanced Award (2008) (TUM: Prof. Ntziachristos), is already commercialized by iThera Medical for macroscopy with systems sold around the world for small animal imaging. In parallel, ERC MSOT funding developed a mesoscopic implementation, termed raster-scan optoacoustic mesoscopy (RSOM), which has demonstrated innovative imaging capacity at 1-5mm depths. Driven by leading dermatologists (TUM: Prof. Biedermann; SUR: Prof. Costanzo) and market leader SMEs in optoacoustic and ultrasound technology (iThera, Rayfos, Sonaxis), INNODERM will design and prototype a handheld, portable, scalable, label-free RSOM device for point-of care dermatology applications, based on recommendations developed under an ERC proof of concept grant (2013) on MSOT. INNODERM brings together key photonic & ultrasound technologies and will validate the technical and economic viability of RSOM in dermatology suites for fast diagnosis and skin disease monitoring. RSOM can go beyond the abilities of current optical or optoacoustic devices and offer a paradigm shift in dermatology imaging, substantiating successful business cases.

The SYSCID consortium aims to develop a systems medicine approach for disease prediction in CID. We will focus on three major CID indications with distinct characteristics, yet a large overlap of their molecular risk map: inflammatory bowel disease, systemic lupus erythematodes and rheumatoid arthritis. We have joined 15 partners from major cohorts and initiatives in Europe (e.g.IHEC, ICGC, TwinsUK and Meta-HIT) to investigate human data sets on three major levels of resolution: whole blood signatures, signatures from purified immune cell types (with a focus on CD14 and CD4/CD8) and selected single cell level analyses. Principle data layers will comprise SNP variome, methylome, transcriptome and gut microbiome. SYSCID employs a dedicated data management infrastructure, strong algorithmic development groups (including an SME for exploitation of innovative software tools for data deconvolution) and will validate results in independent retrospective and prospective clinical cohorts. Using this setup we will focus on three fundamental aims : (i) the identification of shared and unique "core disease signatures” which are associated with the disease state and independent of temporal variation, (ii) the generation of "predictive models of disease outcome"- builds on previous work that pathways/biomarkers for disease outcome are distinct from initial disease risk and may be shared across diseases to guide therapy decisions on an individual patient basis, (iii) "reprogramming disease"- will identify and target temporally stable epigenetic alterations in macrophages and lymphocytes in epigenome editing approaches as biological validation and potential novel therapeutic tool . Thus, SYSCID will foster the development of solid biomarkers and models as stratification in future long-term systems medicine clinical trials but also investigate new causative therapies by editing the epigenome code in specific immune cells, e.g. to alleviate macrophage polarization defects.

Microbes have remarkable capabilities to attach to surfaces of natural and artificial systems, eventually leading to the formation of biofilms and associated chronic and persistent infections. It is extremely appealing to understand how bacteria interact with three- dimensional surface topographies and how to design smart patterns as a strategy to create antifouling and biocidal materials. Here I propose a dynamic strategy, merging verstile and large-scale surface modification teqhniques based on mechanical wrinkling of soft bilayers, that I developed at Imperial College London, microfluidics and microbiology. The goal of MOBILE is investigating the mechanical confinement exerted by non-planar surface curvatures and spatial heterogeneities induced by fluid shear on bacterial initial attachment and removal, in confined environments. Specifically (Aim 1), I will evaluate the combined action of surface topography and fluid shear over bacterial proliferation, motitly and viability, incorporating nano- to micro-scaled wrinkled geometries in microfluidic channels, mimicking biological tissues surfaces and implantable medical devices, testing a series of different clinically relevant bacterial strains (such as Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae). I will also (Aim 2) develop antifouling and removal strategies by investigating the mechanical response of adhered bacteria, using patterned surfaces as stimuli-responsive probes "actuated" by means of mechanical deformation (i.e., by extension and compression of the wrinkled topographies) to induce detachment and surface cleaning under fluid dynamic conditions. Overall, I aim to elucidate new methodologies for bacterial removal at different stages of biofilm formation paving the way towards the development of new classes of biomedical devices and to contribute to an important step in direction of controlling implant-associated infections.

MEFISTO will develop two novel solutions to treat meniscus loss as a strategy for preventing the onset of an epidemic of post-meniscectomy knee osteoarthritis (OA) in Europe. Morphological profiling will identify the population of patients who, after meniscal resection, are at higher risk of early compartment degeneration, providing a personalized approach for the patient. The two different reconstructive strategies are: i) a controlled vascularized bioactive biodegradable meniscal scaffold, which will regenerate the native meniscus. This strategy will address younger patients with early osteoarthritic changes. ii) a bioactive non-biodegradable meniscal prosthesis, which will act as a mechanical unloading device and a drug delivery system, with the capacity to modulate the inflammatory environment. This strategy will address patients with advanced OA. A socio-economic analysis of the efficacy of existing meniscal substitutes will complete the project. This analysis is of vital importance for the European healthcare system, as it will provide a clear understanding of the costs and benefits of current clinical practice and predict the impact of the two new interventions. The technological innovation lies in the development of biologically active functionalized nanobiomaterials that can interact with the surrounding articular tissues. The biodegradable scaffold will promote revascularization in the peripheral zone, while leaving the inner zone avascular, reflecting the native meniscal tissue and functionalization with drug delivery micro/nanoparticles of the non-biodegradable device will provide modulation of inflammation. The impact is expected to be significant as so many patients have undergone or will undergo meniscectomy. The interventions developed in MEFISTO will prevent these patients from receiving joint-sacrificing procedures such as metal prosthesis whilst reducing the social burden, associated costs and high levels of morbidity resulting from OA.

Algae4IBD's mission is to develop commercial products for Inflammatory Bowel Disease (IBD) prevention and treatment using aquatic natural biological resources. With the emerging developments in natural product, notable success has been achieved in discovering natural products and their synthetic structural analogues with anti-inflammatory activity. However, global biodiversity remains a largely unexploited resource for natural bioactive molecules with an enormous potential for developing commercial products with public health benefits. Micro and macroalgae, found in marine and freshwater, have been identified as promising sources of bioactive compounds including small molecules and secondary metabolites with a wide range of bioactivities as an antioxidant, anti-inflammatory and cancer preventive. Consumption of algae could, therefore, provide defence against chronic inflammatory diseases such as IBD, that until date have no effective cure. This project offers nature to bedside approach, using an entire development along the value chain for a new biodiscovery therapeutic approach by developing and examining algae-based compounds for IBD patients while guaranteeing algae's biodiversity preservation. We propose innovative solutions for increasing the use of algae-based ingredients and to ensure the science-based improvement of nutritional quality and its effect on public health. The researchers, companies and hospitals involved in the different stages of the project will use the biodiversity of algae, both micro and macro, as a wide source for bioactive compounds using state-of-the-art cultivation and extraction technologies for obtaining sufficient amounts of the bio-active molecules together with novel processing protocols. It will result in novel algal-based, high-quality bioactive compounds at GMP grade and lower costs for dual purposes – IBD prevention and treatment in relevance to the food as well as the pharmaceutical industries.