A5064330051- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Genetic Syndromes and Imprinting
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Multiple Myeloma Research and Treatments
- Insect and Arachnid Ecology and Behavior
- Adolescent and Pediatric Healthcare
- Protein Degradation and Inhibitors
- Biotin and Related Studies
- Protist diversity and phylogeny
- Cell Adhesion Molecules Research
- Advanced Biosensing Techniques and Applications
- Immunotherapy and Immune Responses
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Planarian Biology and Electrostimulation
- DNA and Nucleic Acid Chemistry
Ludwig-Maximilians-Universität München
2018-2021
Center for Integrated Protein Science Munich
2018-2021
Faculty (United Kingdom)
2021
Institut für Hygiene und Umwelt
1971
Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or flexibility split site selection. Here, we present a technology based on via mRNA trans-splicing (REVeRT). REVeRT is flexible selection can efficiently reconstitute different numerous...
Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm resulting from the malignant transformation of progenitors. Despite intensive chemotherapy leading to initial treatment responses, relapse caused by intrinsic or acquired drug resistance represents a major challenge. Here, we report that histone 3 lysine 27 demethylase KDM6A (UTX) targeted inactivating mutations and mutation-independent regulation in relapsed AML. Analyses matched diagnosis specimens individuals with showed...
Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 6% of FL (19/305). Another 13% (37/286) had amplification, which was associated with higher expression. lead to accelerated autocatalytic conversion from an enzymatically inactive profrom active increased substrate cleavage,...
Abstract Genome-wide DNA demethylation is a unique feature of mammalian development and naïve pluripotent stem cells. Here, we describe recently evolved pathway in which global hypomethylation achieved by the coupling active passive demethylation. TET activity required, albeit indirectly, for demethylation, mostly occurs at sites devoid binding. Instead, TET-mediated locus-specific necessary activating subset genes, including pluripotency germline marker Dppa3 ( Stella, Pgc7 ). DPPA3 turn...
The genetic code of mammalian cells can be expanded to allow the incorporation non-canonical amino acids (ncAAs) by suppressing in-frame amber stop codons (UAG) with an orthogonal pyrrolysyl-tRNA synthetase (PylRS)/tRNAPylCUA (PylT) pair. However, feasibility this approach is substantially hampered unpredictable variations in efficiencies at different codon positions within target proteins. Here, we apply a proteomics-based quantify ncAA rates hundreds endogenous cells. With these data,...
Biological processes in development and disease are controlled by the abundance, localization modification of cellular proteins. We have developed versatile tools based on recombinant E3 ubiquitin ligases that light or drug induced heterodimerization for nanobody DARPin targeted depletion endogenous proteins cells organisms. use this rapid, tunable reversible protein functional studies essential like PCNA DNA repair to investigate role CED-3 apoptosis during Caenorhabditis elegans...
Chemotherapy resistance is the main impediment in treatment of acute myeloid leukaemia (AML). Despite rapid advances, various mechanisms inducing development remain to be defined detail. Here we report that loss-of-function mutations (LOF) histone methyltransferase EZH2 have potential confer against chemotherapeutic agent cytarabine. We identify seven distinct leading loss H3K27 trimethylation via multiple mechanisms. Analysis matched diagnosis and relapse samples reveal a heterogenous...
Abstract Cytosine DNA bases can be methylated by methyltransferases and subsequently oxidized TET proteins. The resulting 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), 5-carboxylcytosine (5caC) are considered demethylation intermediates as well stable epigenetic marks. To dissect the contributions of these cytosine modifying enzymes, we generated combinations Tet knockout (KO) embryonic stem cells (ESCs) systematically measured protein modification levels at transition from naive...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20453-0
Abstract Genome-wide DNA demethylation is a unique feature of mammalian development and naïve pluripotent stem cells. So far, it was unclear how mammals specifically achieve global hypomethylation, given the high conservation (de-)methylation machinery among vertebrates. We found that requires TET activity but mostly occurs at sites where proteins are not bound suggesting rather indirect mechanism. Among few specific genes activated by pluripotency germline marker Dppa3 ( Pgc7, Stella ),...
A pair of orthogonal coiled coils templates highly specific live cell bioconjugation two different proteins. PNA tagging and hybridisation with fluorophore–DNA reporters enables rapid dual receptor internalisation analysis EGFR ErbB2.
ABSTRACT The TET-oxidized cytosine derivatives, 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), are considered DNA demethylation intermediates as well stable epigenetic marks in mammals. We compared modified enzyme levels TET-knockout cells during naive pluripotency exit found distinct differentiation-dependent contributions of TET1 TET2 to 5hmC 5fC formation. divergent argue for independent consecutive oxidation steps vivo with broad implications regulation.
Abstract DNA nanotechnology is an emerging field, which promises fascinating opportunities for the manipulation and imaging of proteins on a cell surface. The key to progress in area ability create nucleic acid-protein junction context living cells. Here we report covalent labelling reaction, installs biostable peptide acid (PNA) tag. reaction proceeds within minutes specific carrying 2 kDa coiled coil Once installed PNA label serves as generic landing platform that enables recruitment...
Bei NMRI-Mäusen führte die zusätzliche Injektion von abgetöteten Zellen vonBordetella pertussis im Vergleich zur alleinigen Applikation Schaferythrocyten zu einer Verstärkung der Primärreaktion und signifikant gesteigerten Präparation des lymphoreticulären Gewebes für immunologische Zweitreaktion, während sich Tertiärreaktion auf cellulärer humoraler Ebene ohne Adjuvans vorbehandelten Kontrolltiere wesentlich weniger stark unterschied. Erstmals zusammen mit zweiten Antigendosis verabfolgte...