Oral delivery of peptide-analogues (a macromolecule) is one of the great challenges in pharmaceutical research. Thus far, only five peptide-analogues have been converted to oral formulations such as tablets/capsules and all face distinct challenges including low bioavailability, dosage control, patient administration inconvenience and restrictions in use (e.g. undesirable food interactions). The BUCCAL-PEP consortium will join hands to develop a multifunctional biomaterial patch which allows, for the first time, buccal (in the cheek) delivery of peptide-analogue therapies, thereby overcoming these challenges through unique integration of a permeation enhancer (SDC) with biomaterials and a peptide-analogue. The novel formulation enables peptides to diffuse across the mucosal multilayer, thereby effectively achieving their intended pharmacological response. The novel approach will result in an improved quality of patient life and increased treatment compliance. Within this project, the consortium will design, select and manufacture a lead product (with Type 2 Diabetes as showcase indication) that will be validated for performance in in vivo large animal studies. Additionally, a Health Technology Assessment will be performed to support the development an evidence-based value proposition and aid in the development of a commercialisation strategy. The final deliverable of the project is a patch that is pre-clinically validated and ready for clinical trials in the desired showcase indication. Overall, the BUCCAL-PEP project will provide a platform technology for oromucosal delivery of peptide-analogues that will be suitable for a broad range of experimental- and approved peptides-analogues therapies across a multitude of disease indications. BUCCAL-PEP will enable novel peptide-based treatments to emerge, which otherwise might not have reached the market due to incompatibility with the currently available administration routes.

Chinese hamster (CHO) ovary cells are the production host for a +50 billion €/yr biopharmaceuticals market. Current CHO production platforms dates to 1980 and are based primarily on media and process optimisation with little consideration to the optimization of the cellular machinery. Fortunately, with the recent sequencing of the CHO genome, an opportunity has opened to significantly advance the CHO platform. The benefit will be advanced production flexibility and a lower production cost. This ITN graduate training programme - eCHO Systems - will blend conventional molecular, cellular, and synthetic biology with genome scale systems biology training in ‘omics data acquisition, biological network modeling, and genome engineering in three interdisciplinary topics: 1) Acquisition of large scale ‘omics data sets and their incorporation into genome-scale mathematical models 2) Development of genome engineering tools, enabling synthetic biology 3) Application of systems and synthetic biology and genome engineering to improve performance of CHO producers The training projects are supported by 15 industrial participants, which will participate in the research and test the results. ESR training will include intense courses focused on computational systems biology, cell biology, business and entrepreneurship. The three universities bring unique complementary skills in systems and synthetic biology, ‘omics technologies, cytometry, and molecular cell biology which will provide depth and breadth to this training. The eCHO Systems will produce four major outputs: General knowledge to improve the productivity, quality, and efficiency of CHO platform cell lines, new systems models for CHO cells, new CHO cell line chassises generated through synthetic biology approaches, high quality education at the graduate level, and a cadre of interdisciplinary graduates poised to transform biopharmaceutical biotechnology.

Carbohydrates are nature’s most abundant and versatile molecules and are involved in several diseases (e.g. diabetes, infection, and cancer metastasis) and other regular processes (e.g. fertilization, immune surveillance and inflammatory responses). Understanding, monitoring and intervening in these processes could be exploited in medicinal therapies, glycobiology, and biomedical research in general. Such applications are predicated on the availability of carbohydrate binding molecules (CBMs) that can selectively and supramolecularly (noncovalently) bind a plethora of carbohydrate molecules ranging from simple monosaccharides to complex oligosaccharides and glycoconjugates. Technologies that can be developed based on CBMs include: the separation and isolation of carbohydrate containing molecules; making carbohydrate sensing and detection devices; enabling selective chemistry on (unprotected) carbohydrates; and a range of bio-functional applications. While the expertise to design, synthesize, study and exploit CBMs is mostly European, the research groups active in this emerging field work independent from each other. With this doctoral network grant, we aim to unite this expertise in the ‘European Network for the Supramolecular Chemistry of Carbohydrates’ (ENSCC). With most of the world’s leading minds on the topic and three companies that are spearheading technologies in the field, our ENSCC will be a European powerhouse that will lead the academic field globally for years to come. This will be achieved by sharing expertise, key-infrastructure, molecular building blocks, and –most importantly– by together training the ten PhDs that this doctoral network grant will fund. This training by a unique network of world-leaders, experts in the field and companies with an interest in CBMs will perfectly position our PhD students to further develop the field by continuing their career in academia and/or industry.

Increased demand for high-quality healthcare for our aging population means that medical device design must satisfy multiple requirements for enhanced biocompatibility, anti-bacterial resistance, manipulation of proteins and improved physical properties. The use of micro/nano structures integral to the surface of a device is a novel way to uniformly tune and control these properties. Polymer materials are ubiquitous in medical devices: in Europe alone, this sector includes 27,000 companies employing 675,000 people with an annual turnover of €110 billion. Precision processing of polymers with micro/nano structures is critical to developing high value-added medical devices. Our ETN focuses on surface integrity issues when micro/nano processing polymers for high performance medical devices. We will develop micro/nano-scale precision manufacturing processes, specifically moulding and forming, and additive and subtractive manufacturing, aimed at 6 classes of medical devices that have particular industry-defined requirements. A strategy to design surface micro/nano structures that provide required functionality for these devices will be established. The surface integrity of these materials and devices will be studied at a fundamental level and correlated with functionality, allowing for optimising the efficacy and performance of the medical devices. Our training will ensure that 12 outstanding ESRs become experts in design and the precision micro/nano processing of polymers for medical devices, thereby improving their career prospects. Our ESRs will undertake interdisciplinary and intersectoral research on polymer micro/nano processing for medical applications and obtain work experience with international industry. They will receive specialised technical training and transferable skills structured around state-of-the-art individual research projects that will provide them with pathways to engineering and manufacturing careers in Europe’s world-leading industry.