Sweet Crosstalk is a multidisciplinary European Training Network built to address the challenge of understanding, at a molecular level, how glycans are involved at the human mucosa–microbiota interface, and how this correlates with human well-being. Research into the human microbiome has reshaped the paradigm of our health and disease. In order to advance further, the time has arrived to understand it at a molecular level. Glycans dominate the microbiota-host interface and are thus ideally positioned to modulate these complex interactions. The research strategy of the Sweet Crosstalk programme focuses on optimal synergy between chemistry and biology. Smart chemistry drives the research to get a molecular-level grip on the role of these glycocodes and their interacting proteins, and advances in biology directs the research. The high quality and credibility of our consortium is ensured by a strong private-public partnership with complementary expertise ranging from chemical synthesis, biochemistry, structural biology to microbiology and cell biology. Our 7 academic groups are all renowned leaders in the glycoscience and microbiome fields, whereas the complementary 4 SMEs are specialized in glycan-based diagnostics and prophylactic therapies. This unique combination of scientific excellence and industry know-how covers the entire process from obtaining fundamental insight to the development of innovative early diagnostics and glycotherapeutics. Sweet Crosstalk also represents a unique research platform to train 15 outstanding Early Stage Researchers to be the new generation of innovative scientists with expert knowledge and skills in interdisciplinary glycoscience and human microbiome research. Our international, intersectoral and interdisciplinary training programme will equip them with the necessary scientific and transferable skills that will make them highly competitive for both top European research institutions and the healthcare/biotech job market.

The ability to selectively extract compounds from waters will transform a multitude of applications, ranging from high-value compound isolation in industrial bioprocesses to removal of pollutants from the environment. However, current filtration technologies are reliant on physicochemical separation strategies requiring high pressure/energy inputs and cannot discriminate specific molecules. BIOMEM will develop novel biomimetic membranes harnessing the unique selectivity of biological transport proteins to facilitate the extraction of single compounds with exquisite specificity. Our concept is to use the unique antiport characteristics of secondary active transport proteins, to move molecules, even at low concentrations, across a polymer membrane against their concentration gradient, deriving energy from the transport of another readily available ion down its own concentration gradient. A novel group of bifunctional polymers will be used to extract membrane proteins, together with their associated lipids, into nanoscale discs. These will then be embedded into polymer membranes which are otherwise impermeable to create membranes that are completely selective for the compound of interest. These bio-inspired membranes will be characterised to understand organisation and function of the membrane, to allow design and optimisation for custom compounds. The produced membranes will be tested for functionality in a proof-of-concept experiment to extract complex high-value oligosaccharides from bulk biomass and phosphate from wastewaters. While initially focussing on those two applications, the separation technology developed will evidence the potential for “plug and play”, bespoke, selective membranes capable of transporting specific molecules through existing or bio-engineered transporters. The developed membranes will be fully scalable and operate at rates comparable to state-of-the-art nanofiltration devices, while simultaneously requiring around 50-75% less energy.

Glycans are carbohydrate structures ubiquitously found on the surface of cells and take part in many biological processes, including cell signaling and neoplasia. Research on glycans is challenging in part due to the limited availability of biologically relevant synthetic glycans and to technical challenges in the analysis of glycan-protein interactions. Glycans also exhibit key roles in viral infections, mediating virus attachment and entry. Human noroviruses (NoVs) are the major cause of viral gastroenteritis and foodborne illnesses causing morbidity, mortality and economic losses. NoV infections are self-limiting in healthy individuals but are associated with severe complications in immunocompromised individuals, the elderly and young children. In addition, frequently occurring new NoV genotypes and variants can cause large outbreaks and epidemics worldwide. Very little is known about NoV infections in most non-human hosts and the close genetic similarities between some animal and human NoVs leads to the realistic hypothesis that the virus might jump the species barrier triggering pandemic variants. Importantly, no therapy is currently available to treat or prevent NoV infections. The requirement for NoVs to attach to specific glycans to infect hosts’ tissues, and cells, has been well established but the underlying mechanisms remain to be elucidated. Going beyond the state-of-the-art, the overall aims of GlycoNoVi is training 9 researchers to address knowledge gaps on NoV glycan interactions and investigate the exciting possibility of developing synthetic glycans as antiviral strategies to treat NoV infection. These aims will be achieved bringing together 5 academic and 3 industrial leaders in glycoscience, glycovirology and NoV field and relying on a multidisciplinary and interconnected approach which is declinate in research-oriented WP1-5 and WP6-8 focused respectively on training, outreach and coordination.