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.

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.

Cells in multicellular organisms organise along body and tissue axes. Cellular processes, such as division plane orientation, must be aligned with these polarity axes to generate functional 3-dimensional morphology, particularly in plants, where cell walls prevent cell migration. While some polarly localized plant proteins are known, molecular mechanisms of polarity establishment or its translation to division orientation are elusive, in part because regulators in animals and fungi appear to be missing from plant genomes. Cell polarity is first established in the embryo, but this has long been an intractable experimental model. My team has developed the genetic, cell biological and biochemical tools that now render the early Arabidopsis embryo an exquisite model for studying cell polarity and oriented division. Recent efforts already led to the unexpected identification of a novel family of deeply conserved polar plant proteins that share a structural domain with key animal polarity regulators. In the DIRNDL project, we will capitalize upon our unique position and foundational results, and use complementary approaches to discover the plant cell polarity and division orientation system. Firstly, we will address the function of the newly identified conserved polarity proteins, and determine mechanistic convergence of polarity regulators across multicellular kingdoms. Furthermore, we will use proteomic approaches to systematically identify polar proteins, and a genetic approach to identify regulators of polarity and division orientation, essential for embryogenesis. We will functionally analyse polar proteins and regulators both in Arabidopsis and the liverwort Marchantia to help prioritize conserved components, and to facilitate genetic analysis of protein function. Finally, we will use a cell-based system for engineering polarity de novo using the regulators identified in the project, and thus reveal the mechanisms that provide direction in plant development.

A major gap in our knowledge of how plants respond to soil salinity is their initial perception of sodium (Na+) ions. Salt is detrimental to plants and soil salinization is an increasing threat to global food security; 6% of the world’s total land area and 20% of irrigated land is affected by salinity. I recently discovered Na+-specific root growth responses of plants and will now exploit these to identify the elusive sodium sensing mechanism of plants. I will use an innovative approach combining genome-wide genetic screens in the model plant Arabidopsis thaliana with dedicated biochemical assays. I will identify candidate Na+-sensor genes through a natural genetic variation screen for the Na+-specific inhibition bending of the root in response to gravity (WP1). In parallel, I will follow a chemical genomics approach to find novel compounds that impair Na+ sensing, and their target proteins in plants (WP2). Subsequent complementary in silico and biochemical approaches will characterize Na+-affinity of the candidates (WP3). Selected putative Na+ sensors will be characterized in planta, by studying their localization, activity, their interactors, and by salt response phenotyping of mutants (WP4). Finally, mutant varieties of sensors will be introduced in the economically relevant crop plant tomato, to provide proof-of-concept for improving salt tolerance by modulating sensor function and implementation in crop improvement programs (WP5). The impact of elucidation of plant Na+ sensing will be monumental; it will reveal how plant responses to salinity stress are driven, and ultimately what is required to cope with salinity. In addition, it will open up new applied directions for agriculture, where improved sodium sensing modules will be used to allow crop growth on marginal, saline soils.