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My PhD work employed genetic and pharmacological manipulations, coupled with highresolution live imaging, to understand intercellular communications during zebrafish cardiovascular development. The heart is the first organ to form, and it is composed of several tissues, among which interactions are crucial. I identified two important interactions between muscular and non-muscular tissues in poorly characterized contexts, and the molecules required for the signalling. First, I discovered an important cellular and molecular crosstalk orchestrating the development of the cardiac outflow tract (i.e., the aortic root in mammals).
Endothelial-derived TGF-beta signalling controls the generation of the local extracellular matrix (ECM). The ECM in turn affects endothelial proliferation as well as smooth muscle cell organization (Boezio et al, 2020; Bensimon-Brito*, Boezio* et al, 2020). In my second project, I investigated the crosstalk between the epicardial layer and the myocardial wall. By generating epicardial-impairment models, I identified a novel role for the epicardium in regulating cardiomyocyte volume during heart development (Boezio et al, 2021). Ultimately, this research contributed to our understanding of how paracrine signalling controls the multicellular interactions integral to organogenesis.
Die Bildung von Blutgefäßen ist essentiell für die Entwicklung und Homöostase von Wirbeltieren und die Endothelzellspezifikation ist ein wichtiger erster Schritt in diesem Prozess. Das früheste bekannte Ereignis bei der Endothelzellspezifikation im Zebrafisch ist die Expression des bHLH-PAS-Transkriptionsfaktor-Gens npas4l. Ich habe eine transgene V5-Linie zum Nachweis des markierten Npas4l auf Proteinebene und eine Gal4-VP16-Reporterlinie zur Visualisierung und Verfolgung von npas4l exprimierenden Zellen in vivo generiert. Beide Linien können bereits in frühen Entwicklungsstadien nachgewiesen werden und komplementieren auch starke npas4l-Mutanten Allele. Um npas4l Reporter exprimierende Zellen in npas4l Mutanten zu verfolgen, habe ich anschließend eine mutierte Variante der Gal4-Reporterlinie erzeugt. Diese Mutante trägt eine Insertion in der Region, die die DNA-Bindedomäne kodiert. Dadurch stört sie die Npas4l-Funktion, aber nicht die Reporterexpression. Dieses mutierte Reporterallel komplementiert nicht die npas4l-Mutanten und zeigt einen starken Phänotyp, was darauf hindeutet, dass es sich um ein funktionelles Nullallel handelt. Phänotypische Analysen zeigten, dass npas4l-Reporter positive Zellen in npas4l-Mutanten nicht spezifizieren oder zur Mittelachse wandern. Stattdessen tragen sie zu den vom intermediären Mesoderm abgeleiteten pronephrischen Tubuli und dem vom paraxialen Mesoderm abgeleiteten Skelettmuskel bei. Ich habe diese Phänotypen durch Einzelzell-RNAseq an den npas4l-Reporter positiven Zellen in npas4l+/- und npas4l-/- Embryonen bestätigt. Zusammen erklären diese beiden alternativen Zellschicksale den Großteil der beobachteten Veränderungen zwischen den Genotypen. Npas4l ist dafür bekannt die Expression der drei Transkriptionsfaktorgene etsrp, tal1 und lmo2 zu fördern. Ich stellte die Hypothese auf, dass das Fehlen jedes dieser Transkriptionsfaktoren in npas4l-Mutanten verschiedene Aspekte des npas4l-Phänotyps verursacht. Daher habe ich Mutantenlinien für alle drei Gene generiert und sie sowohl in vaskulären Reporterlinien als auch im npas4l-Reporterhintergrund analysiert. Die Daten legen nahe, dass verschiedene Gene unterschiedliche Prozesse während der frühen Endothelentwicklung regulieren. In npas4l-/- und etsrp-/- Embryonen differenzieren npas4l-Reporter exprimierende Zellen nicht zu Endothelzellen und tragen stattdessen zur Skelettmuskelzellpopulation bei. In npas4l-/- und tal1-/- Embryonen können npas4l-Reporter exprimierende Zellen nicht migrieren und tragen stattdessen zu der Bildung der pronephrischen Tubuli bei. Um die Beziehung zwischen diesen Faktoren besser zu verstehen, habe ich getestet, ob die Injektion von etsrp-, tal1- oder lmo2-mRNA verschiedene Aspekte des npas4l-Phänotyps retten würde. npas4l-, etsrp- und tal1-Mutanten zeigen alle schwere vaskuläre Phänotypen. Einige Endothelzellen und vaskuläre Strukturen bleiben jedoch in jeder Mutante erhalten. Der Phänotyp ist am stärksten in npas4l-/- Embryonen, aber selbst in diesen Embryonen können einige fli1a-positive Endothelzellen in der Schwanzregion beobachtet werden. Es war unklar, ob sich diese Population von Endothelzellen unabhängig von der Npas4l-, Tal1- und Etsrp-Funktion entwickelt oder als Folge einer restlichen tal1- oder etsrp-Expression unabhängig von Npas4l. Um diese Frage zu untersuchen, habe ich Doppelmutanten generiert und nach dem Vorhandensein von fli1a-positiven Endothelzellen in diesen Mutanten gesucht. Während fli1a-positive Endothelzellen in npas4l-/- und npas4l-/-;tal1-/- Embryonen deutlich vorhanden sind, können keine solchen Zellen in npas4l-/-;etsrp-/- oder etsrp-/-;tal1-/- Embryonen beobachtet werden. Diese Daten deuten darauf hin, dass sich im Zebrafisch keine Endothelzellen entwickeln können, wenn zugleich npas4l und etsrp oder etsrp und tal1 gestört sind. Während der Verlust von etsrp zu stärkeren Defekten in npas4l-Mutanten führt, gibt es keinen zusätzlichen Phänotyp, der durch den Verlust von tal1verursacht wird, was darauf hindeutet, dass die Expression von etsrp, aber nicht die von tal1, unabhängig von Npas4l auftreten kann. Diese Idee wird durch die Beobachtung unterstützt, dass etsrp, aber nicht tal1-Expression in den meisten fli1a-exprimierenden Zellen in npas4l-/- Embryonen beobachtet wird. Dennoch wird der Großteil -Expression durch Npas4l reguliert. tal1-mRNA-Injektionen reichten aus, um eine Wildtyp-ähnliche vaskuläre Musterbildung im Bauchbereich der npas4l-/- Embryonen wiederherzustellen, einschließlich der Rettung sowohl der Zellmigration als auch der Differenzierung. Da Npas4l mehrere unterschiedliche transkriptionelle Effektoren hat, war eine so starke Rettung durch nur einen dieser Effektoren unerwartet. In den geretteten Mutanten wurde die bilaterale Population von npas4l-Reporter-positiven pronephrischen Tubuluszellen nicht entdeckt, aber die Anzahl der ektopischen npas4l-Reporter exprimierenden Muskelzellen war im Vergleich zu nicht injizierten npas4l-Mutanten gleichbleibend.
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The UN 2030 Agenda for Sustainable Development stresses the fundamental role science should play in implementing the 17 Sustainable Development Goals endorsed by the global community. But how can and should researchers respond to this societal demand on science? We argue that answering this question requires systematic engagement with the fundamental normative dimensions of the 2030 Agenda and those of the scientific community—and with the implications these dimensions have for research and practice. We suggest that the production of knowledge relevant to sustainable development entails analytic engagement with norms and values through four tasks. First, to unravel and critically reflect on the ethical values involved in sustainability, values should increasingly become an empirical and theoretical object of sustainability research. Second, to ensure that research on social–ecological systems is related to sustainability values, researchers should reflect on and spell out what sustainability values guide their research, taking into account possible interdependencies, synergies, and trade-offs. Third, to find common ground on what sustainability means for specific situations, scientists should engage in deliberative learning processes with societal actors, with a view to jointly reflecting on existing development visions and creating new, contextualized ones. Fourth, this implies that researchers and scientific disciplines must clarify their own ethical and epistemic values, as this defines accountability and shapes identification of problems, research questions, and results. We believe that ignoring these tasks, whether one is in favor or critical of the 2030 Agenda, will undermine the credibility and relevance of scientific contributions for sustainable development.
Competition over land is at the core of many sustainable development challenges in Myanmar: villagers, companies, governments, ethnic minority groups, civil society organisations and non-governmental organisations from local to the international level claim access to and decision-making power over the use of land. Therefore, this article investigates the actor interactions influencing land-use changes and their impacts on the supply of ecosystem services and human well-being. We utilise a transdisciplinary mixed-methods approach and the analytical lens of the social-ecological systems framework. Results reveal that the links between land-use changes, ecosystem services and human well-being are multifaceted; For example ecosystem services can decline, while human well-being increases. We explain this finding through three different pathways to impact (changes in the resource systems, the governance systems or the broader social, economic and political context). We conclude with implications of these results for future sustainable land governance.
Tissue translocation, multigenerational and population effects of microplastics in Daphnia magna
(2021)
The last century saw the widespread adoption of plastic materials throughout nearly every aspect of our lives. Plastics are synthetic polymers that are made up of monomer chains. The properties of the monomer in conjunction with chemical additives allow plastics to have a sheer endless variety of features and use cases. They are cheap, lightweight, and extremely durable. Plastic materials are often engineered for single-use and in conjunction with high production volumes and insufficient waste management and recycling across the globe, this leads to a large number of plastics entering the environment. Marine ecosystems are considered sinks. However, freshwater ecosystems as entry pathways are highly affected by plastic waste as well. Throughout the past decade, the impact of plastic waste on human and environmental health has received a lot of attention from the ecotoxicological community as well as the public. Small plastic fragments (< 1 mm called microplastics) are a large part of this emerging field of research. Within this, the water flea Daphnia magna is probably the most common organism that is used to assess microplastics toxicity. As a filter-feeding organism, it indiscriminately ingests particles from the water column and is thus highly susceptible to microplastics. For this thesis, we identified some gaps in the available data on the ecotoxicity of microplastics to daphnids. To illuminate some of those gaps the present thesis was aimed at five main aspects:
(1) Tissue translocation of spherical microplastics in Daphnia magna
(2) Investigation of the toxicity of irregularly shaped microplastics
(3) Multigenerational and population effects of microplastics
(4) Comparison of the toxicity of microplastics and natural particles
(5) Effects of particle-aging on microplastics toxicity
The thesis is comprised of three peer-reviewed articles and one so-far unpublished study as “additional results”. The first study was aimed at understanding tissue translocation of spherical microplastics to lipid storage droplets of daphnids. The crossing of biological membranes is discussed as a prerequisite to eliciting tissue damage and an inflammatory response. Previously, researchers reported the translocation of fluorescently labeled spherical microplastics to lipid storage droplets of daphnids, even though no plausible biological mechanism to explain this occurrence. Therefore, in order to learn more about this process and potentially illuminate the mechanism we replicated the study. We were able to observe a fluorescence signal inside the lipid droplets only after increasing the exposure concentrations. Nonetheless, it appeared to be independent of particles. This led to the hypothesis, that the lipophilic fluorescent dye uncoupled from the particles and subsequently accumulated in lipid storage droplets. The hypothesis was further confirmed through an additional experiment with a silicone-based passive sampling device showing that the fluorescence occurred both independent of particles and digestive processes. Accordingly, we concluded that the reported findings were a microscopic artifact caused by the uncoupling of the dye from the particles. Therefore, a fluorescence signal alone is not a sufficient proxy to assume that particles have translocated. It needs to be coupled with additional methods to ensure that the observation is indeed caused by the translocation of particles.
It is still unclear whether the toxicity profile of microplastics is different from that of naturally occurring particles or if they are “just another particle”, as there are innumerable amounts in the natural environment surrounding an organism. The goal of the second study was to compare the toxicity of irregularly shaped polystyrene microplastics to that of the natural particle kaolin. The environment is full of natural non-food particles that daphnids ingest more or less indiscriminately and therefore are well adapted to deal with. Daphnids have a short generation time and usually experience food limitation in nature. Therefore, short-term studies only looking at acute toxicity with ad libitum food availability are not representative of the exposure scenario in nature. For a more realistic scenario, we, therefore, used a four-generation multigenerational design under food limitation to investigate how effects translate from one generation to the next. We observed concentration-dependent effects of microplastics but not of natural particles on mortality, reproduction, and growth. Some of the effects increased from generation to generation, leading to the extinction of two treatment groups. Here, microplastics were more toxic than natural particles. At least part of this difference can be explained by physical properties leading to the quick sedimentation of the kaolin, while microplastics remained in the water column. Nonetheless, buoyancy and sedimentation would also affect exposure in the environment and are likely different for most microplastics than for most naturally occurring particle types.
...
Translation is an important step in gene expression. Initiation of translation is rate-limiting, and it is phylogenetically more diverse than elongation or termination. Bacteria contain only three initiation factors. In stark contrast, eukaryotes contain more than 10 (subunits of) initiation factors (eIFs). The genomes of archaea contain many genes that are annotated to encode archaeal homologs of eukaryotic initiation factors (aIFs). However, experimental characterization of aIFs is scarce and mostly restricted to very few species. To broaden the view, the protein–protein interaction network of aIFs in the halophilic archaeon Haloferax volcanii has been characterized. To this end, tagged versions of 14 aIFs were overproduced, affinity isolated, and the co-isolated binding partners were identified by peptide mass fingerprinting and MS/MS analyses. The aIF–aIF interaction network was resolved, and it was found to contain two interaction hubs, (1) the universally conserved factor aIF5B, and (2) a protein that has been annotated as the enzyme ribose-1,5-bisphosphate isomerase, which we propose to rename to aIF2Bα. Affinity isolation of aIFs also led to the co-isolation of many ribosomal proteins, but also transcription factors and subunits of the RNA polymerase (Rpo). To analyze a possible coupling of transcription and translation, seven tagged Rpo subunits were overproduced, affinity isolated, and co-isolated proteins were identified. The Rpo interaction network contained many transcription factors, but also many ribosomal proteins as well as the initiation factors aIF5B and aIF2Bα. These results showed that transcription and translation are coupled in haloarchaea, like in Escherichia coli. It seems that aIF5B and aIF2Bα are not only interaction hubs in the translation initiation network, but also key players in the transcription-translation coupling.
In order to form an organ, cells need to take up specialized functions and tasks. Cellular specialization is guided by an interplay of chemical signals and physical forces, where one influences the other. One aspect in cellular identity is its shape, which e.g. defines how susceptible the cell may be to intercellular signaling or in which section of the cell cycle it is and therefore can tell us about its current state. Shape changes are introduced by motor proteins that are controlled and activated in a locally confined manner. For my thesis, I was interested to understand better how cellular shape and geometry impacts downstream cell and organ development. What happens if a cell cant transition to a specific shape? How does it affect tissue structure? How does it affect further development?
One regulator of motor proteins like non-muscle myosin is Shroom3, which recently has been been shown to be expressed and involved in the development of the zebrafish lateral line organ (1 ). Development of the lateral line occurs through a migrating cluster of initially about 150 cells, the posterior lateral line primordium (pLLP), which migrates from the anterior (head) to the posterior (tail) while depositing cell clusters in a regular pattern. Literature on development of the lateral line suggests that in order for a cell cluster to be deposited from the pLLP, rosette formation is a key requirement. Therefore our expectation from the shroom3 mutant was that the number of clusters deposited was significantly reduced. To our surprise, when we first inspected the end of migration lateral line phenotype we found many individuals with a significant increase in cell clusters deposited.
This made us re-think the role of Shroom3 during rosette assembly and the processes its involved in.
To study the effects of Shroom3 on lateral line development, a mutant line was generated and crossed with various transgenic lines which express fluorescently labeled proteins that locate to organelles such as the plasmamembrane or the nucleus. Following, the mutant with its fluorescent labels was microscopically imaged under different conditions to quantify and analyze various cell-morphometric features. Even though the zebrafish is a popular model organism and its perfectly suited for developmental biology and advanced microscopy, there were no methods that would allow for a standardized and more automated pipeline of data acquisition and processing.
Therefore, in order to accurately quantify the morphogenic processes Shroom3 is involved in, I developed a new toolset that significantly improved and facilitated my research. The toolset consists of (1) a new sample mounting method that is based on a 3D agarose gel that increases the number of embryos that can be mounted and imaged at once and speeds up the imaging process significantly (2) for subseqent image analysis I developed four programs that automate the process and therefore make the results much more reproducible and the analysis much more efficient. The first program is used for end of migration analyses, to deduce the pattern, count and size of Lateral Line cell clusters. The second is used not for end of migration, but for migration analyses (on timelapse recordings). Besides this it also prepares the images for more advanced downstream migration analyses and allows to analyse fluorescence signal on a second channel. The third program is used to analyse the pLLP only at high spatial resolution and to deduce the cell count, 3D cell morphometrics (like the volume) and cell orientation. The fourth program finally is used downstream of the second and third program and is capable of detecting and comparing them with the look of wildtype rosettes.
Here I show that in absence of Shroom3 rosette formation in the migrating pLLP is destabilized leading to facilitated cell cluster deposition and I show how this might be related to traction forces due to a possible interdependence of pLLP acceleration and speed of migration. Furthermore I show that apical constriction and rosette formation is not blocked in Shroom3 deficient embryos, but that larger rosettes are fragmented into many smaller ones. Finally, I give an outlook on how the absense of Shroom3 and hence the absense of morphological changes may deregulate gene transcription by elevating the levels Atoh1a, a transcription factor necessary for hair cell development.
My results and methodology demonstrate the importance of morphology in guiding developmental processes and how rather small morphological changes on the cellular level can impact further development significantly. My work also shows how powerful modern genetics, imaging and image analysis are and how diverse they are in terms of range of questions they are capable of answering. The methods and tools I developed prepare the ground for at least three quarters of the analyses I carried out and together with the documentation and data I provide, they are highly reproducible. In that regard I am especially happy that one of my developments, an improved sample preparation method, is already used by many different labs all over the world helping them to make their results more reproducible.
Background: The application of chemical dispersants is a common remediation strategy when accidental oil spills occur in aquatic environments. Breaking down the oil slick into small droplets, dispersants facilitate the increase of particulate and dissolved oil compounds, enhancing the bioavailability of toxic oil constituents. The aim of the present work was to explore the effects of water accommodated fractions (WAF) of a naphthenic North Sea crude oil produced with and without the addition of the chemical dispersant FINASOL OSR 52 to adult zebrafish exposed for 3 and 21 d. Fish were exposed to environmentally relevant concentrations of 5% and 25% WAFOIL (1:200) and to 5% WAFOIL+D (dispersant–oil ratio 1:10) in a semi-static exposure setup. Results: The chemically dispersed WAF presented a 20-fold increase of target polycyclic aromatic hydrocarbons (PAHs) in the water phase compared to the corresponding treatment without dispersant and was the only treatment resulting in markedly bioaccumulation of PAHs in carcass after 21 d compared to the control. Furthermore, only 5% WAFOIL+D caused fish mortality. In general, the undispersed oil treatments did not lead to significant effects compared to control, while the dispersed oil induced significant alterations at gene transcription and enzyme activity levels. Significant up-regulation of biotransformation and oxidative stress response genes (cyp1a, gstp1, sod1 and gpx1a) was recorded in the livers. For the same group, a significant increment in EROD activity was detected in liver along with significant increased GST and CAT activities in gills. The addition of the chemical dispersant also reduced brain AChE activity and showed a potential genotoxic effect as indicated by the increased frequency of micronuclei in erythrocytes after 21 d of exposure. Conclusions: The results demonstrate that the addition of chemical dispersants accentuates the effect of toxic compounds present in oil as it increases PAH bioavailability resulting in diverse alterations on different levels of biological organization in zebrafish. Furthermore, the study emphasizes the importance to combine multilevel endpoints for a reliable risk assessment due to high variable biomarker responses. The present results of dispersant impact on oil toxicity can support decision making for oil spill response strategies.
Across the entire animal kingdom, sociality, i.e. the tendency of individual animals to form a group with conspecifics, is a common trait. Environmental changes have to be met with corresponding, quick adaptations. For social species, the presence of conspecifics is important for survival and if social animals are deprived of access to conspecifics, this can lead to strong and lasting changes on a physiological level as well as behaviour. Gene expression changes responsible for these adaptations have so far not been understood in detail. As social isolation leads to changes on a neuronal level, it is important to investigate the gene expression changes that are induced in the brain. In this thesis, next-generation RNA-sequencing was applied to zebrafish, a well-established model organism characterized by its high degree of companionship. Within the entire brain, gene expression was analysed in zebrafish that were raised either with conspecifis or in isolation, ranging from 5 to 21 days post fertilization. Using this approach, several genes were identified that were downregulated by social isolation. In this thesis, I focused on one of these consistently downregulated genes, parathyroid hormone 2 (pth2). The expression of pth2 was demonstrated to be bidirectionally regulated by the number of conspecifics present and to be responsive to changes in the social environment within 30 minutes. Regulation of pth2 does not occur by visual or chemosensory access to conspecifcs, but is mediated by mechanosensory perception of other fish via the lateral line. In an experiment using an artificial mechanical stimulation paradigm, it was shown that the features necessary to elicit pth2 transcription closely mimick the locomotion of actual zebrafish. Other, similar stimulation paradigms are not capable to induce this transcriptional response.
Terpenes are one of the largest and most diverse class of natural products, produced by organisms from all kingdoms of life and with important applications in the pharma, flavor and fragrance industries. Well-known examples of terpenes are the pharmaceuticals artemisinin and taxol, the flavor and fragrance compounds menthol, santalol and sclareol, the structural material polyisoprene and the biofuel precursor farnesene. The methods and results presented in this work offer a variety of ways to modify terpene precursors for the creation of new terpene molecules. The application of these methodologies in well-established production systems could lead to the production of new substances, with applications in the industrial fields of pharmaceuticals, flavors and fragrances, and biofuels.
Global biodiversity is changing rapidly and contemporary climate change is an important driver of this change. As climate change continues, the challenge is to understand how it may affect the future of biodiversity. This is relevant to informing policy and conservation, but it requires reliable future projections of biodiversity. Biodiversity is the variety of life on Earth which includes the diversity of species. The species on Earth are linked in diverse networks of biotic interactions. Interacting species can respond differently to climate change. This can cause spatial or temporal mismatches between interacting species and result in secondary extinctions of species that lose obligate interaction partners. Yet, accounting for biotic interactions in biodiversity projections remains challenging. One way to address this challenge is the use of trait-based approaches because the impact of climate change on interacting species is influenced by species’ functional traits, i.e., measurable characteristics of the species that influence their abiotic and biotic interactions. First, species’ functional traits influence how species respond to climate change. Second, they influence whether the species find compatible interaction partners in reshuffled species assemblages under climate change. Thus, the overarching aim of this dissertation was to explore how trait-based approaches can increase our understanding of how climate change might affect interacting species. For this, I focussed on interactions between fleshy-fruited plants and avian frugivores along a tropical elevational gradient.
I investigated three principal research questions. First, I investigated how traits related to the sensitivity of avian frugivores to climate change and their adaptive capacity vary along elevation and covary across species. I combined estimates of species’ climatic niche breadth (approximating species’ sensitivity) with traits influencing species’ dispersal ability, dietary niche breadth and habitat niche breadth (aspects of species’ adaptive capacity). Species’ climatic niche breadth increased with increasing elevation, while their dispersal ability and dietary niche breadth decreased with increasing elevation. Across species, there was no significant relationship of the sensitivity of the avian frugivores to climate change and their adaptive capacity. The opposing patterns of species’ sensitivity to climate change and their adaptive capacity along elevation imply that species from assemblages at different elevations may respond differently to climate change. The independence between species’ sensitivity and adaptive capacity suggests that it is important to account for both sensitivity and adaptive capacity to fully understand how climate change might affect biodiversity.
Second, I assessed how climate change might influence the co-occurrence of interaction partners with compatible traits, i.e., the functional correspondence of interacting species. I integrated future projections of species’ elevational ranges considering different vertical dispersal scenarios with analyses of the functional diversity of interacting species assemblages. The functional correspondence of fleshy-fruited plants and avian frugivores was lowest if plant and bird species were projected to contract their ranges towards higher elevations in response to increasing temperatures. Contrastingly, if species were projected to expand their ranges upslope, the functional correspondence remained close. The low functional correspondence under a scenario of range contraction indicates that plant species with specific traits might miss compatible interaction partners in future assemblages. This could negatively affect their seed dispersal ability. These results suggest that ensuring the integrity of biotic interactions under climate change requires that species can shift their ranges upslope unlimitedly.
Third, I examined whether avian seed dispersal is sufficient for plants to track future temperature change along the elevational gradient. With a trait-based modelling approach, I simulated seed-dispersal distances avian frugivores can provide to fleshy-fruited woody plant species and quantified the number of long-distance dispersal events the plant species would require to fully track projected temperature shifts along elevation. Most plant species were projected to require several long-distance dispersal events to fully track the projected temperature shifts in time. However, the number of required long-distance dispersal events varied with the degree of trait matching and plant species’ traits. These findings suggest that avian seed dispersal is insufficient for plants to track future temperature change along the elevational gradient as woody plant species might not be able to undergo several consecutive long-distance dispersal events within a short time window, due to their long maturation times. These results also imply that the ability of bird-dispersed plant species to track climate change is associated with the specialization of the seed dispersal system and with plant species’ traits.
Trait-based approaches are promising tools to study impacts of climate change on interacting species. The trait-based approaches that I have developed in this thesis are applicable more widely, e.g., to other types of biotic interactions, or to assess the effects of other drivers of global change. Moreover, these approaches may be further developed to model changes in biotic interactions under global change more dynamically. Taken together, I have shown how a trait-based perspective could help to account for biotic interactions in biodiversity projections. The development of such approaches and the gained knowledge are urgently needed to facilitate the conservation of biodiversity in a rapidly changing world.
Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen–surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin–ligand interaction, supported by present high-throughput “omics” technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.
Camellia sinensis is one of the major crops grown in Taiwan and has been widely cultivated around the island. Tea leaves are prone to various fungal infections, and leaf spot is considered one of the major diseases in Taiwan tea fields. As part of a survey on fungal species causing leaf spots on tea leaves in Taiwan, 19 fungal strains morphologically similar to the genus Diaporthe were collected. ITS (internal transcribed spacer), tef1-α (translation elongation factor 1-α), tub2 (beta-tubulin), and cal (calmodulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. In total, six Diaporthe species, including one new species, Diaporthe hsinchuensis, were identified as linked with leaf spot of C. sinensis in Taiwan based on both phenotypic characters and phylogeny. These species were further characterized in terms of their pathogenicity, temperature, and pH requirements under laboratory conditions. Diaporthe tulliensis, D. passiflorae, and D. perseae were isolated from C. sinensis for the first time. Furthermore, pathogenicity tests revealed that, with wound inoculation, only D. hongkongensis was pathogenic on tea leaves. This investigation delivers the first assessment of Diaporthe taxa related to leaf spots on tea in Taiwan.
Glucose homeostasis is tightly regulated by insulin production from ß-cells and glucagon production from α-cells. Changes in the balance of these hormones lead to Diabetes Mellitus (DM), which is foreseen to be the 7th leading cause of death by 2030, warranting a high demand to identify new therapeutics. DM is characterized by a reduction in ß-cell mass and reduced insulin production from ß-cells. α-cell development and fate mainly depend on the activity of the homeodomain-containing transcription factor Aristaless related homeobox (Arx). Conditional loss- of- function of Arx in α-cells leads to their conversion into functional insulin-producing ß-cells and thus an expansion of ß-cell mass. Therefore, inhibition of Arx is an interesting target for the expansion of ß-cells. The zebrafish model provides a fast, cost-effective and reliable translational platform for drug discovery in an in vivo setting. Here, we screened ~6217 small molecules on a transgenic zebrafish line (TgBAC(arxa:Luc2)) in which the arx promoter drives the expression of the luciferase gene which allows a sensitive and quantitative readout of promoter activity. Small molecule screening allowed us to identify 36 candidate repressors of arxa promoter activity. Furthermore, we started to validate these candidates in other assays. Preliminary results showed that DMAT (a potent CK2 inhibitor) and CNS-1102 (NMDA receptor inhibitor) increase functional ß-cell regeneration. By lineage tracing α-cells during ß-cell regeneration, we could show that both DMAT and CNS-1102 promote α- to ß-cell transdifferentiation. Here, we propose that Casein kinase II and NMDA receptor as potential molecular targets that could be exploited for the treatment of diabetes by generating functional beta-cells from the non-beta-cell progenitor, particularly alpha-cells in situ.