This thesis aims to investigate the effect of tripartite interaction between microbial inoculants, the plant, and herbivore insects on the rhizosphere microbiome and volatilome. We investigated the... Show moreThis thesis aims to investigate the effect of tripartite interaction between microbial inoculants, the plant, and herbivore insects on the rhizosphere microbiome and volatilome. We investigated the rhizosphere microbiome and volatilome of tomato plants exposed to insect herbivory and/or inoculated with beneficial microbes known to trigger ISR. First, we reviewed the abiotic and biotic factors that impact the success of ISR microbial inoculants (Chapter 2). Then, we tested microbial inoculants against different stresses and experimental conditions to compare interactions in variable contexts (Chapter 3). Next, we explored the impact of insect herbivory aboveground, on the volatile and microbial belowground compartment. In Chapter 4 we explored root volatiles under stress in two tomato species to evaluate the genotype impact on the stress-induced root volatilome. In Chapter 5, we studied the impact of endosymbiotic fungi arbuscular mycorrhizal fungi (AMF) on root volatiles in an in vitro bioassay and in a greenhouse setup with herbivory-stressed plants. In Chapter 6, we compared the effect of four phylogenetically diverse bacteria and fungi, inoculated as single-species and as a synthetic community, on the rhizosphere microbiome assembly and volatilome in herbivory-stressed plants. Overall, this thesis delves into overlooked interactions providing novel data on belowground plant-microbe interactions. Show less
Polymyxins are clinically used antibiotics, discovered in mid-20th century. Once abandoned due to excessive nephrotoxicity, they are now used increasingly to address infections caused by multi-drug... Show morePolymyxins are clinically used antibiotics, discovered in mid-20th century. Once abandoned due to excessive nephrotoxicity, they are now used increasingly to address infections caused by multi-drug resistant Gram-negative bacteria.In this thesis, we describe the development and synthesis of analogues of polymyxin, aimed at reducing its associated nephrotoxicity. Analogues were made by semisynthesis, with modifications introduced mostly in the exocyclic portion of the molecule. Especially the introduction of a disulfide bond within the linked lipid helped in reducing the toxicity of the molecules, as evidenced by testing on proximal tubule epithelial cells. For most potent analogues, the antimicrobial activity was completely retained.In addition, this thesis describes studies on the mechanism of action of polymyxin, mostly based on the full stereoisomer of polymyxin B4. This analogue lacks antimicrobial activity, indicating its original stereochemistry to be of utmost importance for its use as an antibiotic.Hybrids based on polymyxin B derivatives are described, addressing non-conventional targets. A hybrid with vancomycin (typically active on Gram-positive bacteria only) shows activity on Gram-negative bacteria. A polymyxin-based hybrid coupled to a peptide with a beta-hairpin motif addresses Gram-negative bacteria, presumably by binding to outer membrane protein BamA. Show less
The haplolepideous mosses (Dicranidae) comprise about 4000 species distributed over a wide range of habitats, with great gametophytic and sporophytic morphological variation. Their monophyly is... Show moreThe haplolepideous mosses (Dicranidae) comprise about 4000 species distributed over a wide range of habitats, with great gametophytic and sporophytic morphological variation. Their monophyly is well supported by the results of several molecular phylogenetic studies, which shed light on their relationships and circumscriptions, and thus also contributed to identify many remaining problems. Dicranidae ordinal classification is not congruent with current relationship hypotheses and is not supported by morphology. Morphological circumscriptions of some families do not correspond to monophyletic groups. Furthermore, the monophyly of many families and genera with weak morphological circumscriptions remains to be tested. In this thesis, systematics and relationships of the leucobryoid mosses and some families and genera segregated from the former Dicranaceae s.l. were studied using molecular phylogenetic methods. 37 out of the 38 haplolepideous moss families were represented by markers from the three genomes (nrITS, nad5, trnS-trnF, atpB-rbcL). Phylogenetic reconstructions were based on maximum parsimony, maximum likelihood, and Bayesian inference. Ancestral state reconstructions, phylogenetic network analysis (NeighborNet), and relationship hypothesis testing (Shimodaira-Hasegawa test) were performed to contribute to the interpretation of the results of the phylogenetic reconstructions. Morphological circumscriptions were evaluated and improved whenever possible, in line with the results of all analyses performed. Show less
In recent decades, climate change has led to more frequent and severe drought events, causing serious consequences such as increased forest mortality and significant crop yield losses.... Show moreIn recent decades, climate change has led to more frequent and severe drought events, causing serious consequences such as increased forest mortality and significant crop yield losses. Understanding how drought affects plants, especially economically important herbaceous species, is crucial for predicting and developing drought-resistant crops. To address this issue, this study analyzed a comprehensive dataset of anatomical and hydraulic traits in different genotypes of Arabidopsis thaliana and tomato, including both wild-type and transgenic mutants. The study also investigated the expression of four well-known drought marker genes associated with ABA-dependent and ABA-independent pathways and the impact of overexpressing the JUNGBRUNNEN1 (JUB1) gene on drought response. The findings revealed that each genotype had a unique set of traits to cope with drought, which could be categorized into two response strategies. One group enhanced their drought resistance through traits like a more negative stem P50, thicker intervessel pit membranes, a more lignified inflorescence stem, and a gradual reduction of the low initial stomatal conductance during drought. This strategy enabled them to maintain a relatively high and stable leaf water potential (Ψl). The second group, represented by JUB1 overexpression genotypes, relied primarily on maintaining a high Ψl which is possibly due to osmoprotectant accumulation in leaves, while the other traits have not been recorded. Overall, this research demonstrated the adaptive capabilities of herbaceous plants to drought conditions, highlighting the intraspecific variation in drought responses that underscores the need for a detailed assessment of drought-responsive traits to improve crop yield in a warming world. Show less
Streptomycetes are soil-dwelling Gram-positive bacteria and can produce clinical drugs and adapt to environmental fluctuations through diverse morphological changes. The morphological development... Show moreStreptomycetes are soil-dwelling Gram-positive bacteria and can produce clinical drugs and adapt to environmental fluctuations through diverse morphological changes. The morphological development of streptomycetes features apical growth, which is determined by a tip-organizing center containing machinery for the synthesis of a cellulose-like glycan deposited at the cell surface. This thesis demonstrated that the cellulose-like glycan likely cellulose and the related synthesis machinery are unique in comparison with other Gram-negative cellulose synthesis systems. It showed that the synthesis of this glycan is performed by the glycosyltransferase ClsA and matured galactose-oxidase protein GlxA. Subsequently, the lytic polysaccharides monooxygenase LpmP and the glucanase ClsZ, adjacent to CslA/GlxA, cooperatively cleave peptidoglycan and create a passage to assist the exposure of this glycan on cell surface. In addition, this thesis also revealed coordination of polar growth determinants is performed by a stomatin-like protein StlP, which locates in the same gene cluster with CslA/GlxA/CslZ/LpmP. Oligomerization of StlP forms a fluid microdomain at hyphal tips, which spatially confines the whole tip organizing center. Furthermore, this thesis further showed that the cellulose-like glycan of Streptomyces coelicolor is responsible for the aggregation of clumps, which is distinct from Streptomyces lividans where this glycan mediates germlings’ aggregation. Show less
Humans and songbirds learn their vocalizations early in life by exposure to the vocalizations of adult conspecifics. Often, better learning outcomes are achieved with live, social, tutors than with... Show moreHumans and songbirds learn their vocalizations early in life by exposure to the vocalizations of adult conspecifics. Often, better learning outcomes are achieved with live, social, tutors than with audio-only exposure to vocalizations. Many researchers argue that this is because social tutor-tutee interactions are important in the vocal learning process. It is unclear, however, whether and to what extent live tutoring also facilitates song learning because it results in multimodal exposure to a tutor, as tutees can both see and hear their tutor, while audio-only tutoring results in unimodal exposure. This thesis investigates whether multi- compared to unimodal exposure affects song learning in zebra finches, the primary experimental animal model for vocal learning studies, by revisiting the zebra finch song learning literature and describing three song tutoring experiments. In these experiments, young birds were provided with audio-only or audio-visual tutor exposure, using one-way mirrors, videos and robotic birds. The results suggest that multi- versus unimodal exposure to a live tutor can affect the timing of vocal development and possibly the amount of vocal learning. Multimodal exposure to artificial tutors made stimulus presentation more salient but did not affect the song learning outcomes assessed in this thesis. Show less
Filamentous Actinobacteria, such as Streptomyces, produce a plethora of chemically diverse bioactive metabolites that have found applications across medicine, agriculture and biotechnology. Yet,... Show moreFilamentous Actinobacteria, such as Streptomyces, produce a plethora of chemically diverse bioactive metabolites that have found applications across medicine, agriculture and biotechnology. Yet, the vast majority of the biosynthetic potential of Actinobacteria remains uncharacterised, largely because their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, preventing the discovery of the cognate natural products. Additionally, only a narrow band of environments and a few taxonomic groups have been explored for gifted Actinobacteria. In this thesis different approaches are described, wherein we combined drug discovery with ecology, aimed at accessing the full potential of Actinobacteria. Bioactive Actinobacteria were isolated from a faecal sample of a 28,000-year-old-mammoth and their taxonomic and metabolic diversity was analysed. Furthermore, the effect of human stress hormones on the production of antibiotics by Streptomyces was investigated, resulting in the discovery of adrenaline as elicitor of siderophore production. This was later shown to be caused by the adrenaline analog catechol, which is ubiquitous in nature. Catechol also elicited the production of angucycline glycosides, well known for their therapeutic potential as anticancer and antibiotic compounds. Lastly, zebrafish were used as an in vivo model to explore the bioactive and functional potential of Actinobacteria within the animal microbiome. Show less
Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria. Classes of antibiotics otherwise limited to the treatment of Gram... Show moreExtending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria. Classes of antibiotics otherwise limited to the treatment of Gram-positive pathogens may be potentiated against Gram-negative bacteria by disruption of their outer membrane. The work described in this thesis focuses on the development of novel synergists designed to selectively disrupt the outer membrane and in doing potentiate the activity of antibiotics that are otherwise inactive against Gram-negative bacteria. Show less
In his dissertation Michiel Hooykaas outlines the results of six empirical research projects focused at biodiversity awareness in the Netherlands, specifically people’s knowledge about animals.... Show moreIn his dissertation Michiel Hooykaas outlines the results of six empirical research projects focused at biodiversity awareness in the Netherlands, specifically people’s knowledge about animals. Providing insight into people’s perception of animal biodiversity is valuable both from a scientific perspective and from the perspective of conservation, as biodiversity loss continues and the relationship between humans and nature is under increasing pressure. The first part of this thesis focuses on species literacy, a newly coined concept that stands for broad and in-depth knowledge about species. Quantitative research projects are described that established the level of species literacy in professionals and laypeople. The second part of this thesis explores the portrayal of animals in cultural products aimed at children. Quantitative content analyses were used to examine the image of animal biodiversity conveyed by two product categories: picture books and clothes. The patterns uncovered in cultural portrayals of animals mirrored the knowledge patterns found in the first part of the dissertation. Animal groups well known by people predominated children’s fashion and picture books, while others were portrayed less frequently and in less specific manners. The revealed patterns imply that Dutch laypeople currently miss out on enriching experiences with biodiversity, and they hold important implications for conservation. The third and final part of this thesis explores, from the perspective of biodiversity communicators, the potential to connect people with biodiversity in places that are becoming increasingly urbanized. As such, promising avenues to foster species literacy and engage people with biodiversity are distilled. Show less
Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that... Show moreDeath in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM. Here we generate embryonic zebrafish models for both the primary and disseminated stage of ocular melanoma. In doing so we can recapitulate the etiology of cancer in its totality. Subsequently, we developed a patient-derived zebrafish xenograft (zf-PDX) model, using spheroid cultures generated from metastatic and primary UM tissues. Harnessing this versatile model, we reveal high sensitivity of circulating UM cells to ferroptosis induction in vivo by Erastin and RSL3, implicating ferroptosis as a new potential therapy in metastatic UM.Increased melanin levels in cutaneous melanoma are associated with decreased patient survival. Melanin levels in primary uveal melanoma patient cells positively correlate with their metastatic potential in zebrafish. Modulation of melanin levels of pan-melanoma cells results in enhanced/reduced metastatic potential upon increased or decreased melanin levels, respectively. Melanin depletion sensitizes melanoma cells to ferroptosis inducers in zebrafish leading to a decreased metastatic burden. Collectively, our data identify melanin biosynthetic enzymes as potential future target to treat melanoma and show that melanin protects metastasizing melanoma cells from ferroptosis. Show less
The work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing... Show moreThe work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing further binding details for inhibitory activity study. The thesis not only describes the extended application to produce peptide-based transition states mimicking PRMT inhibitors but builds an LC-MS/MS method to evaluate CARM1 inhibition and activity. Show less
The experiments described in this thesis employ local lentiviral knockdowns in brain areas of female zebra finches followed by behavioural assays consisting of preference and Go/Nogo tasks.... Show moreThe experiments described in this thesis employ local lentiviral knockdowns in brain areas of female zebra finches followed by behavioural assays consisting of preference and Go/Nogo tasks. Ultimately, the targeted brain areas are extracted for gene expression analyses.The findings suggest that localised reduction of FoxP1 expression in HVC or CMM of female zebra finches does not impair the establishment or maintenance of auditory memories of conspecific song nor the females’ ability to discriminate or categorise auditory stimuli based on spectral or sequential features. Females which received a knockdown of FoxP1 in HVC as adults requested fewer familiar and unfamiliar playbacks and had a lower preference for familiar song than their matched controls. This might suggest that FoxP1 contributes to motivational behaviours in female zebra finches.Gene expression analyses links FoxP1 to pathways that have previously also been associated with FOXP2 in mammals including retinoic acid signalling and the SLIT-ROBO signalling cascade. Altered energy metabolism in different brain areas might also contribute to the observed phenotypes.Ultimately, the results presented in this thesis suggest implications of the transcription factor FoxP1 beyond vocal motor learning which need to be investigated in future studies. Show less
New drugs for use as tuberculosis (TB) treatment are needed due to the constrains of classical antibiotics against TB and the rise of antibiotic-resistant strains, making TB a harder and harder... Show moreNew drugs for use as tuberculosis (TB) treatment are needed due to the constrains of classical antibiotics against TB and the rise of antibiotic-resistant strains, making TB a harder and harder disease to treat. This thesis is focused on using the in vivo whole animalzebrafish embryo model for TB to evaluate potential anti-TB host-directed therapeutics (HDTs) arising from in vitro screens. Although in vitro screens for HDTs using cellular models can be performed at high throughput, a limiting step is the validation in whole animal models and translation of results to clinical applications. Due to the complex infection dynamics of mycobacteria, the use of whole animal models is indispensable in research into TB and the zebrafish model has contributed key findings about host-pathogen dynamics during mycobacterial infection. One of the most promising host targets of HDTs is autophagy, which is recognized as an important host-protective pathway. Boosting autophagy levels using HDTs could be a way to overcome the pathogen’s autophagy evasion strategies and could therefore be a promising therapeutic route. For this thesis we took advantage of the possibilities of the zebrafish embryo model for TB and the zebrafish toolkit to study several autophagy-modulating HDTs as potential anti-TB drugs. Show less
The research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and... Show moreThe research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and glucocorticoids.Leptin plays an important role during TB infection and has a huge impact on insulin sensitivity in zebrafish larvae. Similarly to what has been observed in the murine model, leptin deficiency in zebrafish increased the bacterial burden and mortality during the infection, leading to hyperglycemia and the development of insulin resistance. In addition, a novel SHP-1/SHP-2 inhibitor, NSC-87877, was shown to represent a promising anti-diabetic drug that can be used for further DM2 research, as it is able to rescue the phenotype of the leptin-deficient zebrafish and to restore glucose transport to the tissues. In contrast to metformin, NSC-87877 can act at very early developmental stages and inhibits the function of SHP-1 and factors that underlay impaired glucose metabolism, whereas metformin is mostly known to improve insulin sensitivity. Additionally, treatment with the glucocorticoid beclomethasone attenuates the metabolic changes associated with the infection, and transcriptional alterations induced by beclomethasone treatment suggest that genes involved in glucose metabolism, insulin and leptin signaling all play an important role in the modulation of the metabolism.Our data show that zebrafish larvae represent an interesting model system to investigate the complex pathology of TB, and the studies described in this thesis in which this model has been used have provided novel insights into the molecular mechanisms underlying wasting syndrome and the possibilities for adjunctive glucocorticoid therapy to alleviate this metabolic state. Show less
We developed the bitterling as a unique, well-studied model organism in the area of the evolutionary ecology of brood parasitism. The bitterling-mussel relationship, interspecific mussel host... Show moreWe developed the bitterling as a unique, well-studied model organism in the area of the evolutionary ecology of brood parasitism. The bitterling-mussel relationship, interspecific mussel host preference, and mussel gill structure are studied in detail, to help understand the developmental adaptation of bitterling embryos in response to their mussel hosts. Our complete stage series of the bitterling species R. ocellatus in Chapter 2 is a new, character-based systems that are compatible with the widely-used zebrafish staging system. With time-lapse video, we demonstrated the dynamic processes of hatching moment of the rosy bitterling in real time, which indicates the hatching process is mechanical rather than enzymatic. In Chapter 3, we described the neuroanatomy of bitterling for the first time, filling the gaps in the previous embryonic research in various bitterling taxa. Combined with the molecular analysis of brain early development in Chapter 4, brain development in the rosy bitterling is compared with that in the zebrafish. In Chapter 5, we studied the morphogenetic process of blastokinesis in the bitterling embryo, and its possible relation to brood parasitism. Show less
The explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included... Show moreThe explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included the partitioning of the mixed ancestral glands into two discrete glands devoted for production of venom ormucous respectively, as well as changes in the location, size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth toxin molecular evolutionary history reconstructions have been mostly limited to those types present in only two front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed major toxin types shared across the advanced snakes. Show less
We have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins... Show moreWe have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins of many venomous snakes binds to this receptor in its location at the neuromuscular junction in all vertebrates. Furthermore, some animals have evolved resistance to snake venoms and show modifications in the ligand binding domain of the nAChR which inhibit the binding of snake α-neurotoxins. Our analysis has shown that numerous vertebrate species, most of which were not previously known to possess α-neurotoxin resistance, do actually contain resistance-related modifications. These modifications are present in most of the taxa in our dataset, with the unexpected exclusion of the birds. It was particularly surprising to us that the snake-specialist predatory birds Circaetus pectoralis (black-chested snake eagle) and Sagittarius serpentarius (secretary bird) did not possess resistance modifications. There were also relatively few resistance-related mutations within the mammals. By contrast, there were multiple convergent evolutions of the well-characterised N-glycosylation motif within the squamate reptiles—particularly the snakes. We also identified a number of sites under positive selection, such as mutations to the proline subsite. Future functional testing will be needed to validate that these modifications do indeed confer resistance. To provide functional confirmation that resistance-related modifications do indeed reduce susceptibility to toxins, we used developmental bioassays. These assays showed that two species possessing resistance-related modifications of the nAChR (stickleback and bearded dragon) were less susceptible to the toxic effects of cobra venom than two species that lacked such modifications (zebrafish and chicken). In summary, we demonstrate that the range of mechanisms along with the phylogenetic distribution of resistance to snake α-neurotoxin appears to be more extensive than was previously appreciated. It also shows strong evidence of the convergent evolution of the same resistance mutations in independent linages. Our findings also support the notion that the mutations we have identified in this thesis may represent adaptive change in response to selective pressures exerted by α-neurotoxic snake venoms in an evolutionary arms race. Thus, we conclude that the evolutionary arms race between predator and prey appears to be a pervasive feature of the trophic interactions surrounding venomous snakes, which is shaping the molecular evolution of the nAChR in the vertebrates. Show less
Fungal food spoilage often starts with a contamination with spores. Experimental data strongly indicate the existence of subpopulations of spores with different levels of resistance to preservation... Show moreFungal food spoilage often starts with a contamination with spores. Experimental data strongly indicate the existence of subpopulations of spores with different levels of resistance to preservation methods. In this thesis, the extent of this heterogeneity and the underlying mechanisms using fungal model systems is studied. The role of the genetic background, environmental conditions and the developmental state of the spores were studied, using quantitative imaging, genome and RNA/protein sequencing as well as functional gene analysis. The role of transcription factors in weak acid stress resistance of Aspergillus niger is described. Next, heat resistance of fungal spores of three food spoilage species was quantified and compared. The genomes of Aspergillus niger strains were sequenced and compared revealing the existence of a possible sexual cycle. Melanin of fungal spores impacts UV-C resistance, but not heat resistance and a functional CRISPR/Cas9 genome editing system for Paecilomyces variotii and Penicillium roqueforti is described. Older spores are more heat resistant than younger spores, which can be contributed to differences in compatible solute composition. Additionally, a high cultivation temperature results in fungal spores with high heat resistance, possibly due to heat shock proteins. Show less
Cryogenic electron microscopy (cryo-EM) is a powerful technique used to visualize the inside of cells and to study specific protein complexes. Within this thesis, I describe the use of various cryo... Show moreCryogenic electron microscopy (cryo-EM) is a powerful technique used to visualize the inside of cells and to study specific protein complexes. Within this thesis, I describe the use of various cryo-EM techniques to gain insight into the structural changes of the human pathogen, Vibrio cholerae, as it transitions between different environments. A combination of established and novel techniques is used to prepare the individual cells for cryogenic electron tomography (cryo-ET). For example, I designed a manual plunge freezing apparatus to prepare cryo-EM samples off site and subsequently image them with cryo-ET. Furthermore, I used light microscopy and serial block face scanning EM imaging to visualize changes to the cells’ morphology and structure when transitioning from the environment, into the natural host, the zebrafish (Danio rerio), and back into the environment. In addition, this thesis demonstrates how ultraviolet-C radiation of cryo-EM samples of V. cholerae and the ICP1 bacteriophage can be used to inactivate the pathogen while retaining their ultrastructural details. Lastly, this thesis outlines current and novel methods for processing of larger, more complex samples for cryo-ET. These techniques, together with new models of host-pathogen interactions, offer new tools for exploring microbial interactions with their environments. Show less
The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2... Show moreThe function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades. However, its dual role in both activation and suppression of innate immune responses makes it very difficult to use the available results from basic research for the development of clinical trials. In addition, it is still not clear what is the function of TLR2 in regulating phagocytic cell migration. Therefore, we aimed to determine the function of TLR2 in mycobacterial infection and explore its role in regulating phagocytic cell migration in inflammatory tissue by using a zebrafish larval model in this thesis. We showed that infection of a tlr2 mutant in zebrafish larvae leads to a higher mycobacterial burden, accompanied by a lower number of granulomas and increased extracellular bacterial growth. Through a tail fin wounding and tail fin infection zebrafish model, we demonstrated that tlr2 is involved in modulating leukocyte migration. This thesis provides a better understanding of the functions of TLR2 in innate immune responses to infection and tissue wounding. Show less
