A5018469321- Neuroinflammation and Neurodegeneration Mechanisms
- Zebrafish Biomedical Research Applications
- Immune cells in cancer
- Click Chemistry and Applications
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Nanoplatforms for cancer theranostics
- Glioma Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Immune Response and Inflammation
- interferon and immune responses
- Immune Cell Function and Interaction
- Hippo pathway signaling and YAP/TAZ
- Advanced biosensing and bioanalysis techniques
- Brain Metastases and Treatment
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Radical Photochemical Reactions
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Complement system in diseases
- Sphingolipid Metabolism and Signaling
- Cerebrospinal fluid and hydrocephalus
- Innovative Microfluidic and Catalytic Techniques Innovation
University of Edinburgh
2016-2022
Discovery Centre
2018-2019
Institute of Genetics and Cancer
2018
Edinburgh Cancer Research
2018
European Molecular Biology Organization
2009-2013
European Molecular Biology Laboratory
2012
University of Cologne
2003-2010
Microglia are the resident phagocytes of brain that responsible for clearance injured neurons, an essential step in subsequent tissue regeneration. How death signals controlled both space and time to attract these cells toward site injury is a topic great interest. To this aim, we have used optically transparent zebrafish larval identified rapidly propagating Ca2+ waves determine range microglial responses neuronal cell death. We show while Ca2+-mediated require ATP, spreading intercellular...
Recent advances in bioorthogonal catalysis are increasing the capacity of researchers to manipulate fate molecules complex biological systems. A uncaging strategy is presented, which triggered by heterogeneous gold and facilitates activation a structurally diverse range therapeutics cancer cell culture. Furthermore, this solid-supported catalytic system enabled locally controlled release fluorescent dye into brain zebrafish for first time, offering novel way modulate activity reagents most...
In adult zebrafish, relatively quiescent progenitor cells show lesion-induced generation of motor neurons. Developmental neuron from the spinal domain (pMN) sharply declines already at 48 hours post-fertilisation (hpf). After that, mostly oligodendrocytes are generated same domain. We demonstrate here that within after a lesion or specific genetic ablation neurons 72 hpf, pMN reverts to expense oligodendrogenesis. contrast, dorsal Pax2-positive interneurons was not altered. Larval...
Abstract Microglia are the resident macrophages of brain. Over past decade, our understanding function these cells has significantly improved. do not only play important roles in healthy brain but involved almost every pathology. Gene expression profiling allowed to distinguish microglia from other and revealed that full signature can be observed vivo. Thus, animal models irreplaceable understand cells. One popular study is zebrafish larva. Due their optical transparency genetic...
The zebrafish genome contains ten genes that encode class II cytokine-like peptides, of which the two are related most closely to mammalian interferon gamma (IFN-gamma) were named IFN-gamma1 and IFN-gamma2. Although has become a popular model system study immune mechanisms, although interferons central regulators immunity, cytokines correspond functionally IFN-gamma not been established. We used embryos assay functions IFN-gamma2, have identified subset homologs IFN-responsive as targets in...
The zebrafish genome contains a large number of genes encoding potential cytokine receptor as judged by homology to mammalian receptors. sequences are too divergent allow unambiguous assignments all receptors specific cytokines, and only few have been assigned functions functional studies. Among for class II helical cytokines-i.e., IFNs that include virus-induced Ifns (Ifn-) type (Ifn-γ), together with Il-10 its related cytokines (Il-20, Il-22, Il-26)-only the Ifn--specific complexes...
The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with host tissue. comes a substantial destruction surrounding This leads to activation damage responses resident innate immune protect, repair, and organize wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, CNS, assist cell invasion. Here we report this fatal side effect physiological response In slice coculture...
It is now clear that microglia and macrophages are present in brain tumors, but whether or how they affect initiation development of tumors not known. Exploiting the advantages zebrafish (Danio rerio) model, we showed respond immediately upon oncogene activation brain. Overexpression human AKT1 within neural cells larval led to a significant increase macrophage populations. By using combination transgenic mutant lines, this was caused by infiltration peripheral into mediated via Sdf1b-Cxcr4b...
Somatic mutations activating MAPK/PI3K signalling play a pivotal role in both tumours and brain developmental disorders. We developed zebrafish model of tumour based on somatic expression oncogenes that activate neural progenitor cells. HRASV12 was the most effective inducing heterotopia invasive tumours. Tumours, but not heterotopias, require persistent activation phospho‑(p)ERK express gene signature similar to mesenchymal glioblastoma subtype, with strong YAP component. Application 8-gene...
SN-38, the active metabolite of irinotecan, is released upon liver hydrolysis to mediate potent antitumor activity. Systemic exposure however, also leads serious side effects. To reduce systemic toxicity by controlling where and when SN-38 generated, a new prodrug was specifically designed be metabolically stable undergo rapid palladium-mediated activation. Blocking phenolic OH with 2,6-bis(propargyloxy)benzyl group led significant reduction cytotoxic activity (up 44-fold). Anticancer...
Glioblastoma multiforme is the most common and deadliest form of brain cancer. Glioblastomas are infiltrated by a high number microglia, which promote tumor growth surrounding tissue invasion. However, it unclear how microglia glioma cells physically interact if there differences, depending on cell type. Hence, we have developed novel live imaging assay to study microglia-glioma interactions in vivo zebrafish brain. We transplanted well-established human glioblastoma lines, U87 U251, into...
Abstract Photoactivatable molecules enable ablation of malignant cells under the control light, yet current agents can be ineffective at early stages disease when target are similar to healthy surrounding tissues. In this work, we describe a chemical platform based on amino-substituted benzoselenadiazoles build photoactivatable probes that mimic native metabolites as indicators onset and progression. Through series synthetic derivatives, have identified key groups in benzoselenadiazole...
Analyzing calcium imaging data to understand complex functional networks can be challenging, often requiring multiple tools, custom scripts, and some coding expertise. To address these challenges, we present CalciumNetExploreR (CNER), an R package designed streamline standardize the analysis of time-series from neuronal populations. While originally developed with in mind, CNER's modular design also makes it adaptable other sources neural data, such as fMRI or electrophysiological...
Somite formation in vertebrates depends on a molecular oscillator the presomitic mesoderm (PSM). In order to get better insight into how oscillatory expression is achieved zebrafish Danio rerio, we have analysed regulation of her1 and her7, two bHLH genes that are co-expressed PSM. Using specific morpholino oligonucleotide mediated inhibition intron probe situ hybridisation, find her7 required for initiating posterior PSM, while propagate cyclic intermediate anterior Reporter gene constructs...
Abstract Recent advances in bioorthogonal catalysis are increasing the capacity of researchers to manipulate fate molecules complex biological systems. A uncaging strategy is presented, which triggered by heterogeneous gold and facilitates activation a structurally diverse range therapeutics cancer cell culture. Furthermore, this solid‐supported catalytic system enabled locally controlled release fluorescent dye into brain zebrafish for first time, offering novel way modulate activity...
The Parkinson's disease (PD) risk gene GTP cyclohydrolase 1 (GCH1) catalyzes the rate-limiting step in tetrahydrobiopterin (BH4) synthesis, an essential cofactor synthesis of monoaminergic neurotransmitters. To investigate mechanisms by which GCH1 deficiency may contribute to PD, we generated a loss function zebrafish gch1 mutant ( –/– ), using CRISPR/Cas technology. develop marked neurotransmitter deficiencies 5 d postfertilization (dpf), movement deficits 8 dpf and lethality 12 dpf....
Previously we described direct cellular interactions between microglia and AKT1+ brain tumour cells in zebrafish (Chia et al., 2018). However, it was unclear how these were initiated: also not clear if they had an impact on the growth of cells. Here, show that neoplastic hijack mechanisms are usually employed to microglial processes towards highly active neurons injuries brain. We possess dynamically regulated high intracellular Ca2+ levels. Using a combination live imaging, genetic...
Being recognized as the best-tolerated of all metals, catalytic potential gold (Au) has thus far been hindered by ubiquitous presence thiols in organisms. Herein we report development a truly-catalytic Au-polymer composite assembling ultrasmall Au-nanoparticles at protein-repelling outer layer co-polymer scaffold via electrostatic loading. Illustrating vivo-compatibility novel catalysts, show their capacity to uncage anxiolytic agent fluoxetine central nervous system (CNS) developing...