Polymers are increasingly used as a lightweight and more sustainable alternative to traditional materials like steel. However product developers are not using the polymer materials to their full potential since they don’t fully trust the models of strength and longevity. Having information about the material properties in the bulk of the components during the product development stage will provide this trust. Based on decades of experience from x-ray characterization and instrumentation, our team has developed an x-ray diffraction method to generate this bulk data for semicrystalline polymers. Through the ERC PoC project we will improve the technology by extending the measurement to 3D maps of the sample from the current 2D capability. The increased time in 3D scans will be alleviated through the use of focusing optics to improve the effective opening angle from the x-ray generator and with energy resolving 2D detectors with optimized absorption efficiency in the used energy range. In the project we will furthermore implement the technology in the development process of already selected companies through proto sales of a minimum viable product. The sales will be based on a business model of providing the information from diffraction measurement to the customer as a service rather than through a sale of hardware. This business model lowers the barrier of entry both for the customers and for us as a startup. The lower barrier will help us reach a broader market of SME producers of polymers and aid in the establishing the technology as a generally recognized technique.
Establishing a bio-based economy requires the development of novel biorefineries, where bacterial cell factories are employed for producing added-value compounds from cheap, renewable substrates. CO2 is the ideal feedstock, being the most abundant and virtually unlimited carbon-source on Earth. Novel, highly promising biorefineries aim to utilize genetically engineered bacteria to convert renewable energies and atmospheric CO2 into fuels and chemicals. The enzyme Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the main responsible of CO2 fixation in the biosphere via the Calvin-Benson-Bassham cycle. Despite its wide distribution in the tree of Life, Rubisco is a rather inaccurate enzyme, presenting a tendency to perform an oxygenation side-reaction which results in the formation of 2-phosphoglycolate (2PG). While re-assimilation of 2PG in central metabolism results in net CO2 loss, it can serve as a precursor of glycolate, an attractive, versatile platform chemical. Here, I propose to exploit the sloppiness of Rubisco to implement a novel biorefinery for glycolate production from CO2. Ultimately, I aim to demonstrate feasible microbial synthesis glycolate, where engineered bacterial platforms synthesize this molecule directly from CO2 (as carbon source) and renewable H2 or formate (as energy source). This overarching goal will be pursued through three different, complementary objectives, including: in vivo screening of new, recently described Rubisco isoforms via ad hoc designed 'selection strain'; in vivo directed evolution of the best performing Rubisco isoforms for improving the inherent oxygenation activity; engineering of natural (Cupriavidus necator) and synthetic (Escherichia coli) bacteria autotrophs as cell factories for this process, which will be tested in gas-controlled lab-scale reactors. Eventually, such a novel biorefinery concept will open unprecedented possibilities for the use of CO2 as feedstock for a true biobased economy.
HEDGE-A will address one of the current main challenges of biopharmaceutical production: The scalability of the recombinant adeno-associated virus (rAAV) production process. Big Data approaches like transcriptomic and proteomic analyses will be used together with synthetic biology tools to engineer cell cultures and improve rAAV production. The objectives of HEDGE-A are to design (1) a suitable cell platform to sustain transfection at high cell densities and (2) a scalable upstream bioprocess to improve rAAV biomanufacturing. Access to gene therapy is currently extremely limited due to the high cost of producing rAAVs, leading to expensive treatments and making it virtually inaccessible for the general population or even for diseases requiring high dosage. The main limitation is the poor scalability of the current rAAV production process. HEDGE-A will delve into the molecular limitations of the cellular platform and provide a solution to reduce costs, increase titers and help rAAV-based gene therapies reach the wider population. A cost-effective production process for rAAVs will have a high impact in EU competitiveness as it will open the market for countless gene and cell therapies that are currently non-viable due to the required titers to reach clinical trials. HEDGE-A will present the perfect opportunity for the applicant to join a cutting-edge working environment to fulfil his potential in cell engineering and bioprocess development. The host centre, DTU (Copenhagen) is a leading expert in the field and can provide the essential network to undertake a project like HEDGE-A, bridging academic research and its industrial application.