Biological vesicles hold great promise as nano compartments for various applications such as drug delivery systems, therapeutics, and diagnostic tools but fundamental relationships between material properties and activity are not sufficiently understood to create new products for the benefits of the European society. The overall aim of USOME is to develop characterization approaches for these novel materials enabling proper functionalisation. In particular, this proposal focuses on the development of an entirely novel analytical approach for the analysis of emerging biohybrid vesicles. As model systems we indicate polymersome-hybrids and exosome-hybrids, representing a variation in structure in terms of stability, origin (synthetic/natural) and their hybrid counterparts (proteins/synthetic polymers). Two processes will be studied in detail (i) the encapsulation of proteins in polymersomes; and (ii) the modification of exosomes with proteins and polymers. As a result, advanced analytical methods for characterization of polymersome and exosome hybrids for potential application in therapeutics and diagnostics will be established. The key to this envisaged breakthrough is based on field flow fractionation technique coupled to multiple detectors for elucidation of the structural and compositional distributions in the biohybid systems. This highly topical research will be performed within the individual fellowship of a young, very talented, and curiosity-driven African researcher in a leading European research institute. The combination of his expertise in analytical techniques, the biohybrids formation knowledge of IPF and specific knowledge of the associated partners will enable significant scientific progress in the field and unlocks value for patients. Excellent, customized training will open the ER the doors to a unique research profile, fully embedded in the international scientific community and with outstanding career chances at the fronteers of research.

Early childhood education and care (ECEC) services are increasingly seen as holding the promise of promoting more equal life chances for children by supporting their development and encouraging parental employment. Research shows that ECEC can fulfil such potential, as long as provision is of high quality and reaches the most disadvantaged children. Yet there is ample evidence that disadvantaged children are less likely to attend ECEC institutions. When they do, they are enrolled into settings with lower quality and/or settings catering mostly to other children from disadvantaged families. This latter aspect, relating to settings’ composition, is rarely investigated, but the few existing studies suggest that disadvantaged children “do better in settings with a mixture of children from different social backgrounds”. This research project seeks to offer new evidence on the composition of ECEC settings, to explore the drivers of different levels of concentration of disadvantaged children, and to measure the impact of such levels of concentration on child development. The composition of ECEC settings will be measured in relation to migration status, a salient dimension of educational disadvantage in several European countries. The project focuses on the specific case of Germany, where ECEC attendance varies markedly in relation to both socio-economic status and place of residence. The analysis will draw on different data sources, combining survey data on children and the ECEC they attend with information at a highly disaggregate regional level in order to account for the neighbourhood context in which families live. By combining three levels of analysis – families, ECEC settings, and neighbourhoods – the study develops an multilayered approach which will enrich the child development literature on ECEC services as well as our understanding of educational disadvantage. The findings will strengthen evidence-based knowledge in policy making and service provision in Europe.

The human immune system has evolved sophisticated mechanisms to recognize and eliminate infected, stressed or cancer cells. Presentation of antigens by HLA-I enables the identification of diseased cells by antigen-specific T cells, while changes in HLA-I expression levels are sensed by NK cells. Many human NK cell receptors bind HLA-I; but whether and how NK cells might interact with HLA-II remained unknown. We recently discovered that a subset of commonly expressed HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44, implicating HLA-II in the regulation of NK cells. Remarkably, the strength of NKp44-binding to HLA-DP was dependent on both the HLA-DP allotype and the HLA-DP-presented peptide. The ability of NK cell receptors to bind HLA-II molecules represents a paradigm shift from previous models describing NK cell function largely in the context of HLA-I, and suggests a novel regulatory framework in which NK cells interact directly with HLA-II-expressing cells, including APCs and activated stroma cells. HLA-DP allotypes have been associated with the incidence and outcome of several infectious and inflammatory diseases, and the newly identified interactions between HLA-DP and NKp44 now provide a molecular mechanism implicating NK cells in the pathogenesis of these diseases. As NKp44 and HLA-DP are not expressed in mice, but have evolved recently in primates and humans, studies investigating the underlying mechanisms have to be performed in humans. The applicant proposes an innovative and integrated research program, combining functional immunological and virological approaches with recently developed human organoid systems and proteomics technologies to investigate the impact of interactions between NKp44 and HLA-DP for human diseases, with the ultimate goal to harness NK cells for immunotherapeutic interventions against infections and inflammatory diseases.