Filtern
Volltext vorhanden
- ja (122) (entfernen)
Gehört zur Bibliographie
- ja (122) (entfernen)
Erscheinungsjahr
- 2014 (122) (entfernen)
Dokumenttyp
Schlagworte
- gene expression (5)
- Epigenetik (4)
- Maus (4)
- Bioinformatik (3)
- Genexpression (3)
- antibodies (3)
- ants (3)
- biodiversity (3)
- cancer (3)
- cytoskeleton (3)
- dSTORM (3)
- diversity (3)
- ecology (3)
- evolution (3)
- expression (3)
- metabolism (3)
- phosphorylation (3)
- proliferation (3)
- Bestäuber (2)
- Biodiversität (2)
- Chromatin (2)
- Echinococcus (2)
- Fluoreszenzmikroskopie (2)
- Hochauflösendes Verfahren (2)
- Hochauflösung (2)
- Hämatopoese (2)
- Kilimandscharo (2)
- Kilimanjaro (2)
- MAP-Kinase (2)
- Mikroskopie (2)
- Myc (2)
- Neisseria gonorrhoeae (2)
- PALM (2)
- Regulation (2)
- Signaltransduktion (2)
- Taufliege (2)
- Trypanosoma brucei (2)
- Zellzyklus (2)
- apis mellifera (2)
- bacteria (2)
- bees (2)
- binding (2)
- culture (2)
- drosophila melanogaster (2)
- foraging (2)
- fungal structure (2)
- fungi (2)
- immunoprecipitation (2)
- meiosis (2)
- membrane proteins (2)
- miRNA (2)
- pollination (2)
- protein (2)
- reveals (2)
- sequence alignment (2)
- super-resolution (2)
- telomeres (2)
- "-omics" (1)
- 3D (1)
- 3D microscopy (1)
- ANP (1)
- ARF tumor-suppressor induced lymphomagenes (1)
- Aberration (1)
- Ackerrandstreifen (1)
- African Trypanosomes (1)
- Alignment <Biochemie> (1)
- Alkaline phosphatase (1)
- Ameisen (1)
- Angiogenese (1)
- Angiotensin II (1)
- Anticoagulants (1)
- Antigen CD8 (1)
- Apoptosis (1)
- Argonaute (1)
- Arten-Energy-Theory (1)
- Arteriogenese (1)
- Atriales natriuretisches Hormon (1)
- Atriales natriuretisches Peptid (1)
- B cell receptors (1)
- BBL (1)
- BCL-X-L P53 (1)
- BDNF (1)
- BYL-719 (1)
- Bandscheibenerkrankung (1)
- Bandscheibenkrankheit (1)
- Berger-Parker (1)
- Bestäubungsökologie (1)
- Bienen <Überfamilie> (1)
- Bildauflösung (1)
- Bilderkennnung (1)
- Bilderkennung (1)
- Bioinformatics (1)
- Biologische Uhr (1)
- Biomarker (1)
- Blattschneiderameisen (1)
- Bombus (1)
- Bombus Spp. Hymenoptera (1)
- Bone regeneration (1)
- Bortezomib (1)
- Bos taurus (1)
- Botanischer Garten (1)
- Brain (1)
- Bumblebee (1)
- Butterfly (1)
- C-MYC (1)
- C-MYC PUMA (1)
- CCDC79 (1)
- CK2 (1)
- CLAVATA3 (1)
- Carfilzomib (1)
- Cestoda (1)
- Cestode (1)
- Chirurgie (1)
- Chlamydia (1)
- Chlamydia trachomatis (1)
- Chlamydia-trachomatis-Infektion (1)
- Chromosomal Passenger Complex (1)
- Circadian Rhythms (1)
- Click-Chemie (1)
- Climate Change (1)
- Coagulation factor IX (1)
- Coexpression (1)
- Colonkrebs (1)
- Cord blood-derived hematopoietic stem and progenitor cells (1)
- Coumarin (1)
- Cross-species analyses (1)
- Cytoskeleton Chromosomal Passenger Complex Interaction GAR Domain (1)
- DM-domain gene (1)
- DNA-Methylierung (1)
- DNA-binding domain (1)
- DNA-damage checkpoint (1)
- DNS (1)
- DNS-Schädigung (1)
- DOT1 methyltransferase (1)
- Demethylierung (1)
- Deregulierung (1)
- Deutschland (1)
- Differenzierung (1)
- Dimension 3 (1)
- Diversity (1)
- Domäne <Biochemie> (1)
- Drosophila (1)
- Drosophila melanogaster (1)
- Drought (1)
- Dysplasie (1)
- ERK (1)
- Echinococcosis (1)
- Ectopic bone formation (1)
- Einfluss (1)
- Einzelmolekülmikroskopie (1)
- Embryonale Stammzelle (1)
- Embryonale Stammzellen (1)
- Epigenetic (1)
- Escherichia coli-derived recombinant human bone morphogenetic protein-2 (1)
- Evaluation (1)
- Evolution (1)
- Explorative analyses (1)
- Extrakorporale Befruchtung (1)
- FLS2 receptor (1)
- Fbw7 (1)
- Feature-Selection (1)
- Fisher-Score (1)
- Fluoreszenzlöschung (1)
- Foldamere (1)
- Foldamers (1)
- Forest management (1)
- French-Canadian patients (1)
- GAS2L3 (1)
- GC-A (1)
- Gamet (1)
- Gen notch (1)
- Gen-Knockout (1)
- Gene regulation (1)
- Gene sets (1)
- Genregulation (1)
- Germinative cell (1)
- Geschlechtsbestimmung (1)
- Glutamatrezeptor (1)
- Gonadenentwicklung (1)
- Grasses (1)
- Guanylatzyklase (1)
- Guanylylcyclase (1)
- H-Dimerbildung (1)
- HIV (1)
- HIV-1 protease (1)
- HPA Axis (1)
- HUWE1 (1)
- HeLa cells (1)
- Hematopoietic stem cell ex-vivo expansion (1)
- Herbivory (1)
- Hey Proteine (1)
- Hey proteins (1)
- Hidden-Markov-Modell (1)
- Hill's powers (1)
- Histon-Demethylase UTX (1)
- Histon-Methyltransferase (1)
- Histone (1)
- Honeybee (1)
- Host-parasite interaction (1)
- Huwe1 (1)
- Hydra <Polyp> (1)
- Hypopharyngeal glands (1)
- Hypophysen-Zwischenhirn-System (1)
- Hypothalamisch-hypophysäre Achse (1)
- Höhengradient (1)
- I-tasser (1)
- ITS2 (1)
- Il 4 (1)
- Immunohistochemistry (1)
- Implantat (1)
- Implantatmatrices (1)
- Improved survival (1)
- Innere Uhr (1)
- Insects (1)
- Insulin (1)
- Isoform (1)
- Isomer (1)
- Japankärpfling (1)
- KSR1 (1)
- Kenyon cells (1)
- Kernporen-Komplex (1)
- Kidney cancer (1)
- Kinase inhibitor (1)
- Knochenmark (1)
- Knock-Out (1)
- Knockout <Molekulargenetik> (1)
- Knockout mouse (1)
- Knorpelzelle (1)
- Kollagen (1)
- Kolonkarzinom (1)
- Konstruktive Didaktik (1)
- Korrelative Mikroskopie (1)
- Kreuzvalidierung (1)
- Käfer (1)
- LCK (1)
- LIN9 (1)
- Labial glands (1)
- Landnutzungsgradient (1)
- Leaves (1)
- Legumes (1)
- Lenalidomid (1)
- Lernort (1)
- Lokalisationsmikroskopie (1)
- Lymphozyten (1)
- Lymphozyten mediierter Angriff auf Neurone (1)
- MAP Kinase Signaling (1)
- MAPK (1)
- MAPK signaling cascades (1)
- MIZ1 (1)
- MRT (1)
- MSOT (1)
- MYC (1)
- Makrophage (1)
- Malaria (1)
- Massentrachten (1)
- Mausmodell (1)
- Mbm (1)
- Meiose (1)
- Melanin (1)
- Melphalan (1)
- Mensch (1)
- Mesenchymzelle (1)
- Metabolic Modelling (1)
- Metabolischen Modellierung (1)
- Methylene blue (1)
- Mexican coffee plantations (1)
- Mitose (1)
- Modellierung (1)
- Modifizierung (1)
- Molekulargenetik (1)
- Mucin (1)
- Multiples Myelom (1)
- Mushroom bodies (1)
- Mutagenese (1)
- N-Myc (1)
- NF-KAPPA-B (1)
- Nanos (1)
- Neoblast (1)
- Nervendegeneration (1)
- Nestbau (1)
- Neuroblast (1)
- Neuroblastom (1)
- Neuropeptide (1)
- Northeastern Costa Rica (1)
- Notch Signalweg (1)
- Notch signalling (1)
- Onkolyse (1)
- Oocytes (1)
- Oozyte (1)
- Oozyten (1)
- Osmoregulation (1)
- Out-of-school learning settings (1)
- PEG chemical modification (1)
- PI3K (1)
- PPD (1)
- PRC2 (1)
- Pharmakogenetik (1)
- Phosphatidylinositolkinase <Phosphatidylinositol-3-Kinase> (1)
- Phospho-Akt (1)
- Phosphoproteine (1)
- Photoinduzierter Elektronentransfer (1)
- Phytoplankton (1)
- Plant-herbivore interactions (1)
- Plasmozytom (1)
- Pollination (1)
- Polylactide-co-glycolide (1)
- Pomalidomid (1)
- Profiling (1)
- Prognose (1)
- Prognosis (1)
- Protein p53 (1)
- Protein-Protein-Wechselwirkung (1)
- Proteindomänen (1)
- Proteindynamiken (1)
- PyMOL (1)
- RAS (1)
- RCC (1)
- RNA extraction (1)
- RNA sequence (1)
- RNA splicing (1)
- RNA-SEQ (1)
- RNA-SEQ data (1)
- RNS-Interferenz (1)
- RNS-Spleißen (1)
- Raps (1)
- Receptor kinase (1)
- Rectal cancer (1)
- Regularisierung (1)
- Regulatory Volume Decrease (1)
- Renal cell carcinoma (1)
- Renin Angiotensin System (1)
- Renin-Angiotensin-Aldosteron-System (1)
- Renin-Angiotensin-System (1)
- Repression <Genetik> (1)
- Reprogramming (1)
- Rescorla-Wagner model (1)
- Rind (1)
- SGNH hydrolase (1)
- SH3-Domäne (1)
- SPR-Spektroskopie (1)
- SPRED2 (1)
- SREC-I (1)
- SUN1 (1)
- Salmonella-containing vacuole (SCV) (1)
- Saproxylic beetles (1)
- Saproxylophage (1)
- Schwebfliegen (1)
- Sex determination (1)
- Sexual development (1)
- Sonnenblumen (1)
- Spectral Data Analysis (1)
- Spinnenseide (1)
- Spred Protein (1)
- Spred-Proteine (1)
- Spumaviren (1)
- Stammzelle (1)
- Stationenarbeit (1)
- Stem cell (1)
- Stickstoffmonoxid (1)
- Stoffwechsel (1)
- Support-Vektor-Maschine (1)
- Synaptinemal-Komplex (1)
- Säugetiere (1)
- T-Lymphozyt (1)
- TERB1 (1)
- TLR4 (1)
- TME (1)
- Tanzania (1)
- Tapeworm (1)
- Taxonomie (1)
- Teamwork (1)
- Termiten (1)
- Thrombozyt (1)
- Toll-like-Rezeptoren (1)
- Transkriptionsfaktor (1)
- Transporter SLC5A3 (1)
- Transporter SLC6A6 (1)
- Transposon (1)
- Tumour markers (1)
- Tyrosinase (1)
- Ubiquitin (1)
- VKORC1 (1)
- Vaccinia Virus (1)
- Venlafaxin (1)
- Viabilität (1)
- Virulenzfaktor (1)
- Vitamin K epoxide reductase (1)
- Volumenregulation (1)
- Vorläuferzellen (1)
- Wald (1)
- Warfarin (1)
- WebLogo (1)
- Werk (1)
- Wirkmechanismus (1)
- Y chromosome (1)
- Zelle (1)
- Zellmarker (1)
- Zellmarkierung (1)
- Zellskelett (1)
- Zellteilung (1)
- Zellvolumen (1)
- Zellüberleben (1)
- Zutokin (1)
- Zwei-Poren Domänen Kaliumkanäle (1)
- aberration (1)
- abundance (1)
- acetyltransferase RTT109 (1)
- acoustic signals (1)
- activity rhythm (1)
- adaptive plasticity (1)
- african trypanosomes (1)
- age polyethism (1)
- agroecosystems (1)
- albinaria (1)
- alpha-helical structure (1)
- ambystoma opacum (1)
- amphibian metamorphosis (1)
- amyotrophic-lateral-sclerosis (1)
- analysis of variance (1)
- ant (1)
- antigenetic variation (1)
- antigenic variation (1)
- apoptosis (1)
- arbuscular mycorrhizal fungi (1)
- arginine (1)
- arthropods (1)
- aspergillus fumigatus (1)
- auxin (1)
- background odor (1)
- bee pollinators (1)
- behavior (1)
- beta-oxidation (1)
- binding protein (1)
- biodiversity index (1)
- biodiversity measure (1)
- biogenesis (1)
- bioinformatic (1)
- biological locomotion (1)
- biological sciences (1)
- biominarlization proteins (1)
- bird species richness (1)
- birth rates (1)
- botanical gardens (1)
- brain (1)
- breast-cancer cells (1)
- bumblebee nest density (1)
- butterfly euphydryas-aurinia (1)
- cGMP (1)
- camponotus aethiops (1)
- cancer cell (1)
- cancer treatment (1)
- capacitance (1)
- carcinomas (1)
- carriage (1)
- cations (1)
- cell binding (1)
- cell biology (1)
- cell cultures (1)
- cell death (1)
- cell growth (1)
- cell membranes (1)
- cell-cycle arrest cancer therapy (1)
- chemical diversity (1)
- chemische Modifizierung (1)
- chemotherapy resistance (1)
- chi square tests (1)
- chlamydia trachomatis (1)
- chondrocytes (1)
- chromatin assembly factors (1)
- circadian oscillators (1)
- circadian rhythms (1)
- circular-dichroism (1)
- classical conditioning (1)
- clausiliidae (1)
- clumping factor-B (1)
- cohesin SMC1-Beta (1)
- colonies (1)
- colony (1)
- colorectal cancer (1)
- comb (1)
- commercial grades (1)
- communication (1)
- community structures (1)
- complex (1)
- complex-III (1)
- components (1)
- compound eye (1)
- concept maps (1)
- conceptual change (1)
- conifers (1)
- conservation (1)
- constraints (1)
- copy-number alteration (1)
- cotton rats (1)
- crop yield (1)
- crops (1)
- crosstalk (1)
- cul3 ring ligase (1)
- cycle regulation (1)
- cytokinesis (1)
- cytokinin (1)
- cytokinins (1)
- data sharing (1)
- data-bank (1)
- death rates (1)
- declines (1)
- denritic cells (1)
- density (1)
- dentichasmias busseolae (1)
- deprivation (1)
- determinant (1)
- developing country (1)
- developmental biology (1)
- developmental plasticity (1)
- developmental reprogramming (1)
- diagnosis (1)
- differentiation (1)
- digestive system (1)
- disc deseases (1)
- discrimination (1)
- dominant optic atrophy (1)
- drug discovery (1)
- dung beetle coleoptera (1)
- dye stains-all (1)
- dynamics (1)
- e1071 (1)
- economy services (1)
- ecosystem service (1)
- ecosystem services (1)
- ecosystemservices (1)
- elevational gradient (1)
- embryos (1)
- enhance (1)
- envelope (1)
- environmental cues (1)
- enzyme-linked immunoassays (1)
- epithelial cells (1)
- essential genes (1)
- evolutionary mutant model (1)
- expression site attenuation (1)
- extinction risk (1)
- factor acetylhydrolase activity (1)
- fish (1)
- fish model (1)
- fission yeast (1)
- flow cytometry (1)
- flowers (1)
- fluorescence (1)
- fluorescence microscopy (1)
- fluorescence quenching (1)
- foraging behavior (1)
- forecasting (1)
- forests (1)
- formica cunicularia (1)
- fragmented landscapes (1)
- fruit set (1)
- fruit-quality (1)
- fungal diseases (1)
- fungal pathogens (1)
- gene regulation (1)
- generalization (1)
- generation (1)
- genes and chromosomes (1)
- genome (1)
- geometric mean (1)
- global change (1)
- grasslands (1)
- growth (1)
- guanylyl cylcase A (1)
- habitat destruction (1)
- habitat patch (1)
- habitat quality (1)
- habitats (1)
- helitron (1)
- herbivores (1)
- hippocampal neurons (1)
- hive (1)
- homologous chromosomes (1)
- homology modeling (1)
- honey (1)
- honey bees (1)
- honeybee (1)
- host cells (1)
- host-cells (1)
- human impact (1)
- human mineralocorticoid receptor (1)
- humidity (1)
- hypotonic (1)
- iPS Reprogrammierung (1)
- identification (1)
- idiopathic inflammatory myopathies (1)
- image correlation spectroscopy (1)
- immune receptors (1)
- immune response (1)
- in vitro kinase assay (1)
- in-vitro (1)
- in-vivo (1)
- in-vivo expression (1)
- inducible factor-I (1)
- infections (1)
- inhibitors (1)
- insects (1)
- instensively managed farmland (1)
- interaction networks (1)
- invertebrate herbivory (1)
- isotonic (1)
- katydids orthoptera (1)
- kidneys (1)
- konditioneller Knockout (1)
- lactate dehydrogenase (1)
- lactic acid bacteria (1)
- lactobacillus (1)
- land use (1)
- land-use (1)
- land-use change (1)
- language (1)
- larval density (1)
- leaf-cutting ant (1)
- learning at workstations (1)
- learning curve (1)
- lepidoptera (1)
- life history (1)
- life stage (1)
- linguistic morphology (1)
- lipid bilayer (1)
- lipogenesis (1)
- live-cell (1)
- living cells (1)
- local enhancement (1)
- localization microscopy (1)
- location behavior (1)
- macrophage (1)
- major histocompatibility complex (1)
- malaria (1)
- mammalian septins (1)
- management (1)
- mass-flowering crops (1)
- mechanics (1)
- mechanisms (1)
- medaka (1)
- media geométrica (1)
- medical and biological imaging (1)
- medida de la biodiversidad (1)
- meiotic chromosome dynamics (1)
- melanoma (1)
- membrane characteristics (1)
- membrane organization (1)
- membrane potential (1)
- membrane structures (1)
- memory (1)
- menschlicher Einfluss (1)
- mesenchymal stem cells (1)
- messenger RNA (1)
- metapopulation (1)
- metastasis (1)
- miR-126 (1)
- miR-21 (1)
- miRNS (1)
- microvilli (1)
- mitofilin (1)
- mobility (1)
- model (1)
- modulating (1)
- mole crickets (1)
- molecular biology (1)
- molecular diversity (1)
- molecular mass (1)
- molecular-dynamics simulations (1)
- monoallelic expression (1)
- morphology (1)
- mosquito (1)
- mutation (1)
- nacreous layer formation (1)
- native pollinators (1)
- natural enemies (1)
- natural variation (1)
- naturnahe Habitate (1)
- nervous system (1)
- nest building (1)
- neurone (1)
- neurons (1)
- nonhost plant (1)
- nuclear import (1)
- nuclear-pore complexes (1)
- nympahlidae (1)
- oaks (1)
- odor marks (1)
- oilseed rape (1)
- olfaction (1)
- olyelectrolyte domains (1)
- oncogenic transformation (1)
- oncolytic viruses (1)
- organization (1)
- oryzias-latipes (1)
- p110alpha (1)
- parasite (1)
- patterns (1)
- perception (1)
- pharmacology (1)
- phenotypic plasticity (1)
- phosphorylation sites (1)
- phylogenetic trees (1)
- physical properties (1)
- pi3kinase (1)
- pines (1)
- plant community composition (1)
- plant diversity (1)
- plant hormones (1)
- plantago lanceolata (1)
- platelet activation factor (1)
- platyfish (1)
- pollinators (1)
- polyelectrolyte domains (1)
- population (1)
- populations (1)
- post-harvest quality (1)
- predation (1)
- predation risk (1)
- predictive factors (1)
- presynapse (1)
- prey growth rate (1)
- primary biliary-cirrhosis (1)
- proboscis extension response (PER) (1)
- procambarus-clarkii (1)
- product specificity (1)
- profile distances (1)
- prolactin (1)
- protease (1)
- protein domains (1)
- protein dynamics (1)
- protein-protein interactions (1)
- proteins (1)
- psycholinguistics (1)
- pulmonata (1)
- pupae (1)
- quality (1)
- rana temporaria populations (1)
- reconstruction (1)
- recruitment (1)
- red blood cells (1)
- regression analysis (1)
- regulation (1)
- renal cancer (1)
- renal cell carcinoma (1)
- replicative stress (1)
- resistance (1)
- resource use (1)
- rhythms (1)
- ribosome biogenesis (1)
- riesgo de extinción (1)
- rolling-circle transposons (1)
- saccharomyces cerevisiae (1)
- saccharomyes cerevisiae (1)
- saproxylic Coleoptera (1)
- scanning electron microscopy (1)
- scavender receptor (1)
- scientific computing (1)
- secondary structure (1)
- secreted effector protein (1)
- selection (1)
- self-organization (1)
- semi-natural habitats (1)
- sequence databases (1)
- sequential introduction (1)
- sex chromosomes (1)
- sex determination (1)
- sex-determining region (1)
- shannon index (1)
- shelf life (1)
- signaling (1)
- simpson's index (1)
- single molecule microscopy (1)
- single-trial learning (1)
- small organic osmolytes (1)
- socioeconomic (1)
- sound production (1)
- species diversity (1)
- species gastropoda (1)
- species richness (1)
- species-energy-theory (1)
- spermatocytes (1)
- spiders (1)
- spliceosomes (1)
- splicing factors (1)
- squalius alburnoides (1)
- stable-isotope (1)
- stem cell niche (1)
- strawberry (1)
- structure prediction (1)
- sucrose responsiveness (1)
- sucrose sensitivity (1)
- sunflowers (1)
- super-resolution microscopy (1)
- superresolution (1)
- surface proteins (1)
- surface water (1)
- surgical and invasive medical procedures (1)
- surgical oncology (1)
- symbiotic fungus (1)
- synapse structure (1)
- synapsis (1)
- synaptic localization (1)
- synergistische Effekte (1)
- synthetic lethality (1)
- synthetische Letalität (1)
- systematics (1)
- systemic sclerosis (1)
- systems biology (1)
- teichoic acids (1)
- telomere attachment (1)
- temperate forests (1)
- temporal spillover (1)
- termites (1)
- testis (1)
- tettigoniidae (1)
- therapy (1)
- thermoregulation (1)
- three-dimensional microscopy (1)
- tool (1)
- tousled-like kinases (1)
- toxins (1)
- transcription (1)
- transcription factor MIZ-1 (1)
- transfer RNA-synthetases (1)
- transgenic mice (1)
- transplantation (1)
- transposition (1)
- transposon mutagenesis (1)
- tree plantations (1)
- trees (1)
- triglyceride accumulation (1)
- tropical ecology (1)
- tropische Ökologie (1)
- tumor (1)
- two-color microscopy (1)
- two-pore domain potassium channels (1)
- tyrosine phosphorylation (1)
- ubiquitination (1)
- unstructured proteins (1)
- urban-rural gradient (1)
- vaccinia virus (1)
- variant detection (1)
- variant surface glycoprotein (VSG) (1)
- vibration (1)
- viral entry (1)
- viral replication (1)
- viral transmission and infection (1)
- virulence (1)
- virulence factors (1)
- visual cues (1)
- visual learning (1)
- vocabulary (1)
- volatiles (1)
- waggle dance (1)
- wild (1)
- wild bees (1)
- xanthurenic acid (1)
- xiphophorus maculatus (1)
- zebrafish (1)
- zeitlicher Spillover (1)
- Ökosystem (1)
- Überexpression (1)
- índice de biodiversidad (1)
Institut
- Theodor-Boveri-Institut für Biowissenschaften (122) (entfernen)
Sonstige beteiligte Institutionen
- DNA Analytics Core Facility, Biocenter, University of Würzburg, Würzburg, Germany (1)
- Department of Animal Ecology and Tropical Biology, University of Würzburg, Würzburg, Germany (1)
- Forschungsstation Fabrikschleichach (1)
- Institut für Tierökologie und Tropenbiologie (1)
- Interdisziplinäres Zentrum für Klinische Forschung (ZIKF), Würzburg (1)
- Klinische Mikrobiologie am Universitätsklinikum Erlangen (1)
- Technische Hochschule Wildau (1)
Single-molecule (SM) fluorescence microscopy allows the imaging of biomolecules in cultured cells with a precision of a few nanometres but has yet to be implemented in living adult animals. Here we used split-GFP (green fluorescent protein) fusions and complementation-activated light microscopy (CALM) for subresolution imaging of individual membrane proteins in live Caenorhabditis elegans (C. elegans). In vivo tissue-specific SM tracking of transmembrane CD4 and voltage-dependent Ca(2+) channels (VDCC) was achieved with a precision of 30 nm within neuromuscular synapses and at the surface of muscle cells in normal and dystrophin-mutant worms. Through diffusion analyses, we reveal that dystrophin is involved in modulating the confinement of VDCC within sarcolemmal membrane nanodomains in response to varying tonus of C. elegans body-wall muscles. CALM expands the applications of SM imaging techniques beyond the petri dish and opens the possibility to explore the molecular basis of homeostatic and pathological cellular processes with subresolution precision, directly in live animals.
Dynamic interactions and their changes are at the forefront of current research in bioinformatics and systems biology. This thesis focusses on two particular dynamic aspects of cellular adaptation: miRNA and metabolites.
miRNAs have an established role in hematopoiesis and megakaryocytopoiesis, and platelet miRNAs have potential as tools for understanding basic mechanisms of platelet function. The thesis highlights the possible role of miRNAs in regulating protein translation in platelet lifespan with relevance to platelet apoptosis and identifying involved pathways and potential key regulatory molecules. Furthermore, corresponding miRNA/target mRNAs in murine platelets are identified. Moreover, key miRNAs involved in aortic aneurysm are predicted by similar techniques. The clinical relevance of miRNAs as biomarkers, targets, resulting later translational therapeutics, and tissue specific restrictors of genes expression in cardiovascular diseases is also discussed.
In a second part of thesis we highlight the importance of scientific software solution development in metabolic modelling and how it can be helpful in bioinformatics tool development along with software feature analysis such as performed on metabolic flux analysis applications. We proposed the “Butterfly” approach to implement efficiently scientific software programming. Using this approach, software applications were developed for quantitative Metabolic Flux Analysis and efficient Mass Isotopomer Distribution Analysis (MIDA) in metabolic modelling as well as for data management. “LS-MIDA” allows easy and efficient MIDA analysis and, with a more powerful algorithm and database, the software “Isotopo” allows efficient analysis of metabolic flows, for instance in pathogenic bacteria (Salmonella, Listeria). All three approaches have been published (see Appendices).
Embryonale Stammzellen (ESCs) sind durch zwei charakteristische Eigenschaften definiert. Neben einer kontinuierlichen Selbsterneuerungskapazität weisen ESCs die Fähigkeit auf, in alle Zelltypen der drei Keimblätter differenzieren zu können. Diese Eigenschaften werden unter anderem durch ein Netzwerk wichtiger Pluripotenzfaktoren als auch durch epigenetische Mechanismen reguliert, welche die Transkription von Pluripotenz- und Differenzierungsgenen kontrollieren.
In murinen ESCs sind an der Repression von Differenzierungsgenen auch Polycomb group (PcG) Proteine beteiligt. Diese Proteine bauen zwei Chromatin-modifizierende Komplexe auf, die als Polycomb repressive complex 1 bzw. 2 (PRC1 bzw. PRC2) bezeichnet werden. Nach dem klassischen Modell der Polycombfunktion, katalysieren PRC1 und PRC2 gemeinsam zwei charakteristische Histonmodifikationen, die zur Repression PRC-spezifischer Zielgene beitragen. Zahlreiche Studien in den letzten Jahren belegen, dass der Proteinaufbau der PRC1 Komplexe stark variieren kann, wobei die Familie der Polycomb group RING finger (Pcgf) Proteine eine wichtige Rolle spielt. In diesem Zusammenhang definieren einzelne Pcgf Paraloge (Pcgf1 – 6) verschiedene PRC1 Varianten (PRC1.1 – 1.6), die Komplex-spezifische Bindestellen im Genom aufweisen. Diese Erkenntnisse lassen auf unterschiedliche Mechanismen der PRC1 Varianten und Pcgf Paralog-spezifische Funktionen schließen, die zum jetzigen Zeitpunkt nur wenig erforscht sind.
Für manche Pcgf Paraloge sind wichtige Rollen in verschiedenen Stammzelltypen und während der iPS Reprogrammierung bekannt. Pcgf1 (Nspc1), Pcgf2 (Mel18) und Pcgf4 (Bmi1) zeigen eine Funktion in verschiedenen adulten Stammzellen. Pcgf4 spielt darüber hinaus eine wichtige Rolle in der murinen iPS Reprogrammierung. Für Pcgf6 (Mblr) wird eine Pluripotenz-assoziierte Funktion angenommen, denn Pcgf6 ist das einzige Pcgf Paralog, das eine erhöhte Expression in murinen ESCs aufweist, die jedoch im Verlauf der ESC-Differenzierung absinkt. Außerdem zeigen murine Pcgf6 KD ESCs eine verminderte Expression der Pluripotenzgene Oct4, Sox2 und Nanog, eine De-Repression mesodermaler und Testes-spezifischer Gene als auch eine erhöhte Tendenz zur hämatopoetischen Differenzierung. Wie genau Pcgf6 an der Regulation dieser Prozesse in murinen ESCs beteiligt ist, ist nicht bekannt.
In der hier vorliegenden Dissertation wurde die Funktion von Pcgf6 in der murinen iPS Reprogrammierung untersucht. Da bereits für Pcgf4 eine Rolle in der Reprogrammierung somatischer Zellen gezeigt wurde und Pcgf6 eine erhöhte Expression in ESCs aufweist, wurde auch für Pcgf6 eine Funktion in der iPS Reprogrammierung angenommen. Zunächst konnte in dieser Arbeit gezeigt werden, dass Pcgf6 während der iPS Reprogrammierung verstärkt exprimiert wird und in iPS Zellen eine ESC-ähnliche Expression aufweist. Darüber hinaus konnte Pcgf6 in Kombination mit Oct4, Klf4 und c-Myc spezifisch den Transkriptionsfaktor Sox2 in der iPS Reprogrammierung ersetzen. Zudem wurden für OPKM-induzierte iPS Zellen charakteristische Eigenschaften pluripotenter Zellen nachgewiesen. Außerdem konnte eine Rolle von Pcgf6 als Enhancer-Faktor für die iPS Reprogrammierung ausgeschlossen werden, da die Überexpression von Pcgf6 zusammen mit den OSKM Faktoren keine additiven Effekte auf die Reprogrammierungseffizienz erzielte. Im Gegensatz dazu führte der Knockdown (KD) von Pcgf6 in embryonalen Mausfibroblasten (MEFs) zu verminderten Effizienzen nach OSKM Reprogrammierung. Darüber hinaus handelte es sich bei der Mehrheit der AP+ Kolonien, die unter Pcgf6 KD Konditionen entstanden, um partiell-reprogrammierte iPS Zellen.
Zusammengefasst zeigen die Ergebnisse der hier vorliegenden Arbeit, dass Pcgf6 ein neuer und essentieller Faktor der iPS Reprogrammierung ist, der in Kombination mit Oct4, Klf4 und c-Myc spezifisch den Transkriptionsfaktor Sox2 ersetzen kann.
Eye structure, activity rhythms, and visually-driven behavior are tuned to visual niche in ants
(2014)
Insects have evolved physiological adaptations and behavioral strategies that allow them to cope with a broad spectrum of environmental challenges and contribute to their evolutionary success. Visual performance plays a key role in this success. Correlates between life style and eye organization have been reported in various insect species. Yet, if and how visual ecology translates effectively into different visual discrimination and learning capabilities has been less explored. Here we report results from optical and behavioral analyses performed in two sympatric ant species, Formica cunicularia and Camponotus aethiops. We show that the former are diurnal while the latter are cathemeral. Accordingly, F. cunicularia workers present compound eyes with higher resolution, while C. aethiops workers exhibit eyes with lower resolution but higher sensitivity. The discrimination and learning of visual stimuli differs significantly between these species in controlled dual-choice experiments: discrimination learning of small-field visual stimuli is achieved by F. cunicularia but not by C. aethiops, while both species master the discrimination of large-field visual stimuli. Our work thus provides a paradigmatic example about how timing of foraging activities and visual environment match the organization of compound eyes and visually-driven behavior. This correspondence underlines the relevance of an ecological/evolutionary framework for analyses in behavioral neuroscience.
In contrast to c-Myc, a deregulated expression of the MYCN gene is restricted to human neuroendocrine tumours. In most cases, the excessive activity of N-Myc results from a MYCN amplification. In neuroblastoma, amplification of MYCN is a predictor of poor prognosis and resistance to therapy. The inability to target the N-Myc protein directly necessitates the search for alternative targets. This project aimed at identifying genes specifically required for growth and survival of cells that express high levels of N-Myc using high-throughput shRNA screening combined with next generation sequencing. The identification and analysis of these genes will shed light on functional interaction partners of N-Myc.
We screened a shRNA library containing 18,327 shRNAs and identified 148 shRNAs, which were selectively depleted in the presence of active N-Myc. In addition, shRNAs targeting genes that are involved in p53 and ARF turnover and apoptosis were depleted in the cell population during the screen. These processes are known to affect N-Myc-mediated apoptosis. Consequently, these results biologically validated the screen. The 148 shRNAs that showed a significant synthetic lethal interaction with high levels of N-Myc expression were further analysed using the bioinformatics program DAVID. We found an enrichment of shRNAs that target genes involved in specific biological processes. For example, we validated synthetic lethal interactions for genes such as, THOC1, NUP153 and LARP7, which play an important role in the process of RNA polymerase II-mediated transcription elongation. We also validated genes that are involved in the neddylation pathway.
In the screen we identified Cullin 3, which is a component of the BTB-CUL3-Rbx1 ubiquitin ligase that is involved in the turnover of Cyclin E. Depletion of cullin 3 and activation of N-Myc was found to synergistically increase Cyclin E expression to supraphysiological levels, inducing S-phase arrest and a strong DNA damage response.
Together with results from a proteomics analysis of N-Myc associated proteins, our results lead us to the following hypothesis: In a neuroblastoma cell, the high levels of N-Myc result in a conflict between RNA polymerase II and the replication machinery during S-phase. The newly identified interaction partners of N- Myc are required to solve this conflict. Consequently, loss of the interaction leads to a massive DNA damage and the induction of apoptosis. In addition, inhibition or depletion of the essential components of the neddylation pathway also results in an unresolvable problem during S-phase.
Neisseria gonorrhoeae is a human-specific pathogen that causes gonorrhea. It is defined as a super bacterium by the WHO due to the emergence of gonococci that are resistant to a variety of antibiotics and a rapidly increasing infection incidence. Genome-wide investigation of neisserial gene essentiality and novel virulence factors is urgently required in order to identify new targets for anti-neisserial therapeutics. To identify essential genes and new virulence factors, a high-density mutant library in N. gonorrhoeae MS11 was generated by in vitro transposon mutagenesis. The transposon library harbors more than 100,000 individual mutants, a density that is unprecedented in gonococcal research. Essential genes in N. gonorrhoeae were determined by enumerating frequencies of transposon insertion sites (TIS) with Illumina deep sequencing (Tn-seq). Tn-seq indicated an average distance between adjacent TIS of 25 bp. Statistical analysis unequivocally demonstrated 781 genes that were significantly depleted in TIS and thus are essential for Neisseria survival. A subset of the genes was experimentally verified to comprise essential genes and thus support the outcome of the study. The hereby identified candidate essential genes thus may constitute excellent targets for the development of new antibiotics or vaccines.
In a second study, the transposon mutant library was applied in a genome-scale “negative-selection strategy” to identify genes that are involved in low phosphate-dependent invasion (LPDI). LPDI is dependent on the Neisseria porin subtype PorBIA which acts as an epithelial cell invasin in absence of phosphate and is associated with severe pathogenicity in disseminated gonococcal infections (DGI). Tn-seq demonstrated 98 genes, which were involved in adherence to host cells and 43 genes involved in host cell invasion. E.g. the hypothetical protein NGFG_00506, an ABC transporter ATP-binding protein NGFG_01643, as well as NGFG_04218 encoding a homolog of mafI in N. gonorrhoeae FA1090 were experimentally verified as new invasive factors in LPDI. NGFG_01605, a predicted protease, was identified to be a common factor involved in PorBIA, Opa50 and Opa57-mediated neisserial engulfment by the epithelial cells. Thus, this first systematic Tn-seq application in N. gonorrhoeae identified a set of previously unknown N. gonorrhoeae invasive factors which demonstrate molecular mechanisms of DGI.
Plant diversity is known to affect success of host location by pest insects, but its effect on olfactory orientation of non-pest insect species has hardly been addressed. First, we tested in laboratory experiments the hypothesis that non-host plants, which increase odour complexity in habitats, affect the host location ability of herbivores and parasitoids. Furthermore, we recorded field data of plant diversity in addition to herbivore and parasitoid abundance at 77 grassland sites in three different regions in Germany in order to elucidate whether our laboratory results reflect the field situation. As a model system we used the herb Plantago lanceolata, the herbivorous weevil Mecinus pascuorum, and its larval parasitoid Mesopolobus incultus. The laboratory bioassays revealed that both the herbivorous weevil and its larval parasitoid can locate their host plant and host via olfactory cues even in the presence of non-host odour. In a newly established two-circle olfactometer, the weevils capability to detect host plant odour was not affected by odours from non-host plants. However, addition of non-host plant odours to host plant odour enhanced the weevils foraging activity. The parasitoid was attracted by a combination of host plant and host volatiles in both the absence and presence of non-host plant volatiles in a Y-tube olfactometer. In dual choice tests the parasitoid preferred the blend of host plant and host volatiles over its combination with non-host plant volatiles. In the field, no indication was found that high plant diversity disturbs host (plant) location by the weevil and its parasitoid. In contrast, plant diversity was positively correlated with weevil abundance, whereas parasitoid abundance was independent of plant diversity. Therefore, we conclude that weevils and parasitoids showed the sensory capacity to successfully cope with complex vegetation odours when searching for hosts.
Pocket-Proteine und E2F-Transkriptionsfaktoren regulieren die Expression von Zellzyklus-assoziierten Genen und spielen eine zentrale Rolle bei der Koordination der Zellteilung, Differenzierung und Apoptose. Störungen dieser Signalwege tragen zur Entstehung zahlreicher Tumorentitäten beim Menschen bei. Trotz der intensiven Untersuchung der Zellzyklusregulation sind viele Details noch unverstanden.
Der LIN-Komplex (LINC / DREAM) ist ein kürzlich entdeckter humaner Multiprotein-komplex, welcher dynamisch mit Pocket-Proteinen und E2F-Transkriptionsfaktoren interagiert. Eine essentielle Komponente des LIN-Komplexes ist das LIN9-Protein. Um die Funktion dieses Proteins bei der Zellzyklusregulation und Tumorentstehung genauer untersuchen zu können, wurde in unserer Arbeitsgruppe ein konditionelles Lin9-Knockout-Mausmodell etabliert.
Primäres Ziel der Arbeit war es, den Phänotyp embryonaler Fibroblasten (MEFs) aus diesen Mäusen zu charakterisieren. Bereits kurz nach Inaktivierung von Lin9 konnte ein stark verlangsamtes Zellwachstums beobachtet werden. In Lin9-depletierten MEFs wurden multiple mitotische Defekte detektiert, die u. a. strukturelle Auffälligkeiten des Spindelapparates, aberrante Zellkerne, Störungen der Chromosomensegregation sowie zytokinetische Defekte umfassen und in einer dramatischen Zunahme polyploider und aneuploider Zellen resultieren. Im Langzeitverlauf führen diese erheblichen Aberrationen zu einer vorzeitigen zellulären Seneszenz. Wird diese durch das Large T-Protoonkogen durchbrochen, können sich MEFs an den Verlust von Lin9 adaptieren, zeigen dann jedoch eine hochgradige genomische Instabilität und Substrat-unabhängiges Wachstum im Weichagar als Zeichen onkogener Transformation.
Im zweiten Abschnitt der vorliegenden Arbeit wurde die Genexpression in Lin9-defizienten MEFs mittels quantitativer Real Time-PCR untersucht um zu klären, ob die beschriebenen Defekte auf Veränderungen der transkriptionellen Aktivität zurück-zuführen sind. Dabei wurde eine erhebliche Reduktion der Expressionslevel mitotischer Gene nach Verlust von Lin9 beobachtet. Des Weiteren wurden zur Klärung der zu Grunde liegenden molekularen Mechanismen Chromatin-Immunpräzipitations-Experimente (ChIP) durchgeführt. Im Vergleich zu Kontrollzellen wurden dabei in Lin9-defizienten Zellen signifikante epigenetische Veränderungen bezüglich aktivierender Histon-Modifikationen an den Promotoren mitotischer Lin9-Zielgene festgestellt.
Im letzten Abschnitt der Arbeit sollten die Auswirkungen des heterozygoten Verlustes von Lin9 analysiert werden. Dabei zeigte sich, dass Lin9-haploinsuffiziente Zellen normal proliferieren, obwohl die Expression verschiedener G2/M-Gene leicht vermindert war. Es wurde jedoch eine Schwächung des mitotischen Spindelkontrollpunktes und in der Folge über mehrere Zellgenerationen eine Zunahme polyploider Zellen beobachtet. Mit Weichagar-Assays konnte gezeigt werden, dass bereits der heterozygote Verlust des Lin9-Gens zur onkogenen Transformation beiträgt.
Zusammengenommen dokumentieren diese Studien, dass LIN9 eine entscheidende Bedeutung bei der Regulation von Zellzyklus-assoziierten Genen spielt und sowohl einen essentiellen Faktor für die Zellproliferation darstellt als auch durch die Gewährleistung genomischer Stabilität tumorsuppressive Eigenschaften aufweist.
Localization microscopy is a class of super-resolution fluorescence microscopy techniques. Localization microscopy methods are characterized by stochastic temporal isolation of fluorophore emission, i.e., making the fluorophores blink so rapidly that no two are
likely to be photoactive at the same time close to each other. Well-known localization microscopy methods include dSTORM}, STORM, PALM, FPALM, or GSDIM. The biological community has taken great interest in localization microscopy, since it can enhance the resolution of common fluorescence microscopy by an order of magnitude at little experimental cost.
However, localization microscopy has considerable computational cost since millions of individual stochastic emissions must be located with nanometer precision. The computational cost of this evaluation, and the organizational cost of implementing the complex algorithms, has impeded adoption of super-resolution microscopy for a long time.
In this work, I describe my algorithmic framework for evaluating localization microscopy data.
I demonstrate how my novel open-source software achieves real-time data evaluation, i.e., can evaluate data faster than the common experimental setups can capture them.
I show how this speed is attained on standard consumer-grade CPUs, removing the need for computing on expensive clusters or deploying graphics processing units.
The evaluation is performed with the widely accepted Gaussian PSF model and a Poissonian maximum-likelihood noise model.
I extend the computational model to show how robust, optimal two-color evaluation is realized, allowing correlative microscopy between multiple proteins or structures. By employing cubic B-splines, I show how the evaluation of three-dimensional samples can be made simple and robust, taking an important step towards precise imaging of micrometer-thick samples.
I uncover the behavior and limits of localization algorithms in the face of increasing emission densities.
Finally, I show up algorithms to extend localization microscopy to common biological problems.
I investigate cellular movement and motility by considering the in vitro movement of myosin-actin filaments. I show how SNAP-tag fusion proteins enable imaging with bright and stable organic fluorophores in live cells. By analyzing the internal structure of protein clusters, I show how localization microscopy can provide new quantitative approaches beyond pure imaging.
Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(−)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(−) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(−) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(−) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(−) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(−) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.