GlySign is a research training network for the translation of glycomic clinical biomarkers for Precision Medicine (PM). Complex, distinctive changes occur in the glycomics profiles or - Glycan Signatures - of human glycoproteins during progression of many chronic diseases including cancer and inflammatory conditions. The three beneficiaries of the GlySign Consortium have been instrumental in contributing to knowledge in this field through development of glycomics technology and discovery of clinically important novel glycan biomarkers in a variety of diseases. Glycan signatures have great potential for adding useful diagnostic and prognostic information in PM. However, advancement of this field is slow because (a) glycans have immense structural complexity resulting in major technical challenges for their analysis and (b) there is a lack of experts with required glycoanalytical skills. GlySign will address this gap by training six young scientists within an innovative training-by-research programme with high industrial-academic mobility to eventually push forward the translation of novel glycomics-based diagnostic tools into clinical practice. This will be achieved by further developing a range of selective and sensitive glycomics technologies for the analysis of samples from patients and healthy controls in close collaboration between industry/academia as well as clinical chemists and clinicians who will be the end users of GlySign’s final products. To this end, we will focus the training on clinical glycomics applied to four model diseases implicating changes in the glycosylation of circulating proteins specific to disease progression or subtype, i.e. diabetes, prostate cancer, fetal and neonatal alloimmune thrombocytopenia and rheumatoid arthritis. Due to its strong industrial and translational focus, GlySign will, moreover, fill a current gap in the market by establishing new in vitro diagnostic platforms for clinical exploitation of glycomic biomarkers for PM.

Colorectal cancer (CRC) is a major worldwide cancer burden with about 1.4 million cases in 2012 and an annual mortality of approximately 700,000. Early detection is crucial as treatment is most efficient in early stages where population based screenings could substantially reduce incidence and mortality. Current screening techniques are invasive or lack sensitivity and specificity. Moreover, the molecular mechanisms leading to the formation of different antigens suggested as CRC biomarkers and potential therapeutic targets are poorly understood, especially with regard to carbohydrate-based molecules, such as glycans. Enhancing our understanding of the structure-function relationship of glycosylation in CRC could lead to the discovery of improved diagnostic and prognostic biomarkers and pave the way for nov-el therapeutic targets. Building on an established network of analysts with many years of experience in (glyco)proteomics and biomarker research, in collaboration with colleagues in the field of glycobiology and glyco-immunology, GlyCoCan will develop new methods, and use current state of the art methods, to investigate the role of glycosylation in many different aspects of CRC. The GlyCoCan multi-disciplinary network will principally be a training programme with a substantial industrial focus on technology transfer and teaching of internationally adopted biopharma regulations (GMP, ISO9001, ICH guidelines). The underlying specific research objectives will be addressed within individual ESR projects, giving rise to a generation of ESRs whose main focus is investigating and tackling the challenges of the role of glycosylation within CRC and other diseases. The network will address the currently unmet need for glycosylation researchers with an inter-disciplinary perspective to fully exploit the immense potential of the young scientific field of glyco-oncology and to set them on a path to successful and productive careers in academic and industrial collaborations.

The advance of nanomedicine requires the development of novel materials with tailored properties, controlled circulation, optimal targeting and therapeutic efficacy after administration. Nanomaterials engineered with glycans offer multiple possibilities for nanomedicine as these biomolecules when arranged on a nanomaterial surface display strong binding to specific receptors while at the same time the glyco coating can restrict unspecific interactions with proteins, helping to avoid the mononuclear phagocyte system and improved biocompatibility in vivo. The NanoCarb Network will develop novel and well-characterised nanomaterials with synthetic and native N-glycans that will be used for therapeutics and guide development of new drug delivery applications. The project will train early stage researchers at the interface of nanotechnology and glycosciences, with the overall goal of achieving a new generation of professionals in nanomedicine for a prospective career in both academia and industry. To achieve this goal a multidisciplinary consortium has been created including universities, research centres and SMEs with broad expertise ranging from nanotechnology, carbohydrate chemistry, glycoprofiling and in vitro – in vivo screening specialists. An ambitious training plan will be implemented including courses, outreach activities, participation in seminar, and workshops for the development of scientific and transferable skills.

Virtually all mammalian cells are covered with a dense and complex coat of sugar chains (glycans) known as the glycocalyx, which is essential for multicellular life. Interfacing the cell surface with the cellular environment, glycocalyces accomplish critical functions in signalling and communication between cells, controlling tissue development, homeostasis and repair, inflammatory and immune responses, neuronal connectivity, and symbiosis with gastrointestinal bacteria. However, when dysregulated, they can promote immune diseases, neurodegeneration and cancer. While glycocalyces act as the first line of defence against pathogens, some pathogens have evolved to hijack the glycocalyx to promote infection. Despite their importance, mammalian glycocalyces remain the ‘dark matter’ of biology, under-studied owing to the historical lack of preparative and analytical tools to probe the local molecular composition and transient interactions of molecules within glycocalyces, and missing physics rules to interpret experimental observations. The GLYCOCALYX Doctoral Network will provide 15 doctoral candidates with training in bespoke physics, chemistry and biology methods – essential disciplines that will be integrated to enable us to resolve the dynamic organisation of glycocalyces, and how they perform the many selective barrier functions essential to multicellular life. We will develop chemical, analytical and computational TOOLS for glycocalyx research and use them to define physics and molecular RULES that underpin glycocalyx self-organisation and barrier functions. Practical scientific training in state-of-the-art research methods will be complemented by a coordinated programme of industry-relevant transferable skills tailored to prepare the doctoral candidates for future careers in the sector of medical technologies and its underpinning innovations.