Monitoring of human health and the prevention/treatment of (infectious) diseases strongly depend on accurate and efficient detection, identification and tracking of pathogens or biomarkers. Key features of such a diagnostic tool that enable this are speed, accuracy and availability at the point-of-care. Current molecular diagnostic solutions do not meet these requirements due to the fact that they often need to be performed in a centralized fashion. However, the incredible advances in CRISPR-Cas technology in recent years provide an opportunity to change this. By taking advantage of the innate specificity of CRISPR-Cas we have previously developed a highly sensitive and accurate proof-of-concept diagnostic tool with promising results. The potential for implementation is unfortunately impaired by the fact that the workflow comprises of multiple steps that increases hands-on time, room for human error and the undesirable implications this has. To mitigate this, we propose a solution that entails developing a novel approach based on a thermostable RNA polymerase that allows for the condensation of the current workflow into a shorter 1-step protocol. Once such a protocol has been developed, an assay will be developed for one of the causative pathogens of chronic obstructive pulmonary disease (COPD). Technical feasibility of the assay will be demonstrated, in collaboration with an academic hospital, by characterizing the developed assay on relevant clinical samples. This will provide insight into the real-life performance when compared to the current gold standard (PCR) as well as ease-of-use in a relevant context. Furthermore, the feasibility of the value proposition and potential for commercialization will be thoroughly assessed. Not only will this ERC-PoC project shed light on the potential for our improved CRISPR-Cas based diagnostic tool in the context of COPD, a sense of broad applicability in other human Point-of-Care diagnostics applications will be gained.

Plant species diversity is often associated with reduced disease risk. Yet, the scientific literature on diversity-disease relationships is unclear, showing conflicting relationships. This conflict highlights a major knowledge gap in our understanding of the mechanisms underpinning the diversity-disease relationships. Overcoming this gap is essential for transforming agricultural systems from monocultures that are sensitive to disease outbreaks to diverse cropping systems that are intrinsically resilient to pathogens. I aim to significantly advance our understanding of diversity-disease relationships in plants. I will transform our knowledge on belowground plant-pathogen interactions by integrating three advances from animal epidemiology. 1 Host quality Diversity in epidemiological traits has proven key to understanding disease dynamics in animals. I will systematically quantify such variation in plants and their consequences for disease risk. 2 Pathogen protection Microbes can protect animals from pathogen infection. I will investigate the role of symbiotic mycorrhizal fungi (AMF) in belowground pathogen protection in diverse plant communities. 3 Contact networks Pathogen transmission ultimately depends on contacts within the community. Plants are obviously sessile, but their root systems are not. By navigating the soil, they may interact with different neighbouring plants. I will examine how the nature of these root contact networks affects disease risk. I propose that plant traits are a bridging link between these epidemiological advances. I will use experimental and modelling approaches with a range of grassland species and three soil-borne fungal pathogens. I aim to transform our understanding of belowground plant-pathogen interactions in biodiverse systems with multiple pathogens, stimulate crossovers with phytopathology and animal epidemiology, and provide a knowledge base to design agricultural systems that are intrinsically resilient to pathogens.

Next generation biomass resources such as marine seaweed and micro-algae have advantages in comparison to terrestrial lignocellulosic biomass as they can grow on non-arable land at higher areal productivities. Aquatic biomass can provide renewable energy (e.g. biodiesel, bioethanol and biogas) as well as high-value molecules such as carotenoids, fatty acids, carbohydrates, proteins and food fibres, which can be used in food, feed, cosmetics, biomaterials, nanostructures and pharmaceutical industries. However, in order to greatly increase the economic viability of aquatic biomass, all components found in the biomass need to be valorized. Unfortunately, valorization of multiple biomass components is not possible using current/conventional biorefinery technologies, where up to 90% of the biomass is being treated as a waste. The value of these broken-down compounds sees more than a ten-fold reduction, rendering the biorefinery economically unfeasible. Therefore, in furtherance of developing multiproduct biorefineries, selective and economically feasible extraction and separation technologies will need to be developed and implemented. Significant microalgal cell disruption and extraction advances have been recently made by employing external fields such as lasers, ultrasonic waves and microwaves, in combination with less aggressive solvents and ionic liquids. However, the issues regarding the use of chemicals and multiple separation stages remain. Thus, we are proposing a game-changing single-step disentanglement and separation of microalgal high-value components by using acoustic waves at different frequencies allowing thus a complete process fine-tuning and eliminating the need for chemicals. Moreover, by including our previously-developed ultrasound disruption technology, the whole cell breakdown, extraction and separation steps could be reduced to one single process governed and finely-tuned through the employed frequency ranges.

Eukaryotic Argonaute proteins are known for their central role in RNA interference pathways. Yet, the evolutionary origin of Argonaute proteins lies in prokaryotes, where other proteins essential for RNA interference are absent. Therefore, prokaryotic Argonaute proteins (pAgos) must have distinct ancestral functions. Although a handful of closely related pAgos interfere with exogenous DNA invaders such as plasmids, pAgos are extremely diverse in terms of sequence conservation and domain architecture. In addition, many pAgos genetically associate with various putative enzyme domains, which suggests that they are functionally interdependent. As such, different pAgos must rely on distinct mechanism and are expected to fulfil a range of different roles. Therefore, the function of most pAgos remains completely unknown. The COMPASS project will map the function of unexplored pAgo systems, in which pAgos associate with auxiliary proteins. I hypothesize that in these systems, pAgo binds exogenous DNA sequences in a guide-dependent manner. This can result in the recruitment and/or activation of the auxiliary proteins. As pAgo-associated auxiliary proteins are homologous to proteins involved in DNA recombination, NAD+ turnover, or protein deacetylation, these pAgo systems are expected to fulfil completely novel roles ranging from stimulating horizontal gene transfer to triggering programmed cell death. The uncharacterized roles of these pAgo systems and the mechanisms underlying their functionality will be elucidated by a multidisciplinary approach combining microbiology, protein biochemistry, and X-ray crystallography techniques. Not only will the results facilitate a deeper understanding of the evolutionary diversification of pAgos, it will also enable the repurposing of programmable pAgo systems for the development of genetic tools that facilitate guide sequence-directed DNA recombination and high-sensitivity detection of target DNA sequences.

Tourism is a pervasive phenomenon as are the contemporary global dialogues about slavery and colonial heritage. Globally, the tangible and intangible remnants of slavery and the colonial past generate tensions that can yield both productive and destructive outcomes. In such locations, visceral narratives and experiences that evoke these tensions are being crafted for visitors. The FRICTIONS project will unravel how tourism transforms and narrates this heritage while navigating the ensuing contestations and tensions. In our increasingly diverse society at risk of polarisation, the stories we tell about our history can directly address challenges such as racism, discrimination and inclusion. FRICTIONS develops an interdisciplinary theory of cultural memories linked to slavery and colonial heritage tourism. The project employs an innovative and rigorous qualitative methodological research design to explore the tensions arising from slavery and colonial heritage tourism within three key geographical contexts: (a) Ghana-Suriname-Netherlands; (b) Angola-Brazil-Portugal and; (c) Namibia-Brazil-Germany. FRICTIONS will map and examine: (1) to what extent and under which conditions sites of slavery and colonial heritage are transformed into tourism products, practices and performances; (2) the ways in which such transformations create frictions of space; and (3) how these frictions influence broader societal narratives concerning the collective heritage of slavery and colonial heritage. FRICTIONS is an ambitious project combining insights from cultural geography, tourism studies and heritage and memory studies to advance conceptual knowledge that renders the transformative role of tourism into wider societal discussions of slavery and colonial heritage beyond specific places. Such insights inform ongoing societal debates on dealing with this shared heritage. This is important and urgent for charting a path towards a truly inclusive and just global society.