A5047802150- Invertebrate Immune Response Mechanisms
- Genomics and Chromatin Dynamics
- Insect symbiosis and bacterial influences
- Neurobiology and Insect Physiology Research
- Epigenetics and DNA Methylation
- Insect Utilization and Effects
- Developmental Biology and Gene Regulation
- Insect Resistance and Genetics
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Immune Cell Function and Interaction
- Reproductive System and Pregnancy
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- Chromosomal and Genetic Variations
- Protein Degradation and Inhibitors
- Plant Molecular Biology Research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA modifications and cancer
- Congenital heart defects research
- Advanced biosensing and bioanalysis techniques
- Exercise and Physiological Responses
- Advanced Fluorescence Microscopy Techniques
- vaccines and immunoinformatics approaches
- Genetics, Bioinformatics, and Biomedical Research
The Gurdon Institute
2018-2025
University of Cambridge
2018-2025
University of Copenhagen
2021-2024
Wenner-Gren Foundations
2016-2020
Stockholm University
2013-2020
Modified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. How this may sustain the epigenome cell identity remains unknown. Here we show that transmission of histone-based information maintains fidelity embryonic stem plasticity. Asymmetric segregation H3-H4 in MCM2-2A mutants compromised mitotic inheritance histone modifications globally altered epigenome. This included widespread spurious deposition repressive...
The precise control of gene expression by transcription factor networks is crucial to organismal development. predominant approach for mapping factor-chromatin interactions has been chromatin immunoprecipitation (ChIP). However, ChIP requires a large number homogeneous cells and antisera with high specificity. A second approach, DamID, the drawback that levels Dam methylase are toxic. Here, we modify our targeted DamID (TaDa) enable cell type-specific in mammalian systems, generating an...
Temporal patterning of neural progenitors is an evolutionarily conserved strategy for generating neuronal diversity. Type II stem cells in the Drosophila central brain produce transit-amplifying intermediate (INPs) that exhibit temporal patterning. However, known factors cannot account diversity adult brain. To search missing factors, we developed NanoDam, which enables rapid genome-wide profiling endogenously tagged proteins vivo with a single genetic cross. Mapping targets transcription...
Abstract The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility disorders after birth. Because it not well understood how the placenta fetus respond acute lung- inflammation, we characterize response pulmonary lipopolysaccharide exposure across 24 h in using multi-omics, imaging integrative analyses. Unlike organs, mount strong inflammatory immune responses, upregulates immuno-modulatory genes, particular IL-6...
Our goal is to characterize the innate immune response against early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed a controlled way have become increasingly important, including fruitfly Drosophila melanogaster. Many mutants affect germline and, as consequence, also system itself, making it difficult ascribe their phenotype tissue. Only during past decade, mutations been induced systematically somatic study control...
Apart from their role in cellular immunity via phagocytosis and encapsulation, Drosophila hemocytes release soluble factors such as antimicrobial peptides, cytokines to induce humoral responses. In addition, they participate coagulation wounding, development. To assess during infection with entomopathogenic nematodes, we depleted plasmatocytes crystal cells, the two classes of present naïve larvae by expressing proapoptotic proteins order produce hemocyte-free (Hml-apo, originally called...
Abstract Transposable elements are an abundant source of transcription factor binding sites, and favorable genomic integration may lead to their recruitment by the host genome for gene regulatory functions. However, it is unclear how frequent co-option transposable as is, which programs they contribute compare devoid elements. Here, we report a initiation-centric, in-depth characterization transposon-derived landscape mouse embryonic stem cells. We demonstrate that substantial number element...
Histone modifications play a key role in regulating gene expression and cell fate during development disease. Current methods for cell-type-specific genome-wide profiling of histone require dissociation isolation cells are not compatible with all tissue types. Here we adapt Targeted DamID (TaDa) to recognize specific marks, by fusing chromatin-binding proteins or single-chain antibodies Dam, an Escherichia coli DNA adenine methylase. When combined TaDa, this enables chromatin intact tissues...
Many genes are co-expressed and form genomic domains of coordinated gene activity. However, the regulatory determinants domain co-activity remain unclear. Here, we leverage human individual variation in expression to characterize co-regulatory processes underlying systematically quantify their effect sizes. We employ transcriptional decomposition extract from RNA data an component related revealed by positioning. This strategy reveals close 1,500 domains, covering most expressed genes, which...
Abstract The Notch signalling pathway is a master regulator of cell fate transitions in development and disease. In the brain, promotes neural stem (NSC) proliferation, regulates neuronal migration maturation can act as an oncogene or tumour suppressor. How NOTCH its transcription factor RBPJ activate distinct gene regulatory networks closely related types vivo remains to be determined. Here we use Targeted DamID (TaDa), requiring only thousands cells, identify binding NSCs their progeny...
Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading general weakening (cachexia). Both adaptive innate immunity are affected. The fruit fly Drosophila melanogaster has an including cells the myeloid lineage (hemocytes). To study physiology during leukemia, we established three models by driving expression a dominant-active version Ras oncogene (RasV12 ) alone or combined with knockdowns tumor suppressors in...
Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via Ras V12 -overexpression in postmitotic salivary glands (SGs) Drosophila larvae, we overrode adaptability growth signals and induced hypertrophy. The accompanied loss integrity, recognition by cellular immunity, cell death all buffered blocking stress signaling a genuine...
Insect hemolymph coagulation: Kinetics of classically and non-classically secreted clotting factors Schmid et al., 2019. The linked article demonstrates the localization two secretory proteins in Drosophila melanogaster, Prophenoloxidase (PPO2) Transglutaminase-A (Tg) hemocytes as well clot with different tissue-specific drivers. Here we provide further data for usefulness GFP-tagged version crosslinking enzymes that are involved hardening. morphology crystal cells is described using PPO2...
Abstract Histone modifications play a key role in regulating gene expression and cell fate during development disease. Current methods for cell-type specific genome-wide profiling of histone require dissociation isolation cells are not compatible with all tissue types. Here we adapt Targeted DamID to recognise marks, by fusing chromatin binding proteins or single-chain antibodies Dam, an E. coli DNA adenine methylase. When combined (TaDa), this enables intact tissues organisms. We first...
To analyze gene regulatory networks active during embryonic development and organogenesis it is essential to precisely define how the different genes are expressed in spatial relation each other situ. Multi-target chromogenic whole-mount situ hybridization (MC-WISH) greatly facilitates instant comparison of expression patterns, as allows distinctive visualization mRNA species contrasting colors same sample specimen. This provides possibility relate domains topographically with high accuracy...
Summary Temporal patterning of neural progenitors is an evolutionarily conserved strategy for generating neuronal diversity. Type II stem cells in the Drosophila central brain produce transit-amplifying intermediate (INPs) that exhibit temporal patterning. However, known factors cannot account diversity adult brain. To search new factors, we developed NanoDam, which enables rapid genome-wide profiling endogenously-tagged proteins vivo with a single genetic cross. Mapping targets...
Abstract Many genes are co-expressed and form genomic domains of coordinated gene activity. However, the regulatory determinants domain co-activity remain unclear. Here, we leverage human individual variation in expression to characterize co-regulatory processes underlying systematically quantify their effect sizes. We employ transcriptional decomposition extract from RNA data an component related revealed by positioning. This strategy reveals close 1,500 domains, covering most expressed...