A5032584613- RNA modifications and cancer
- Genetic and Kidney Cyst Diseases
- Protist diversity and phylogeny
- Ferroptosis and cancer prognosis
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer, Lipids, and Metabolism
- SARS-CoV-2 and COVID-19 Research
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- SARS-CoV-2 detection and testing
- Cancer-related molecular mechanisms research
- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- Viral-associated cancers and disorders
- Genomics and Chromatin Dynamics
- Parasites and Host Interactions
- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- Enzyme Structure and Function
- Circular RNAs in diseases
- Renal and related cancers
- Cancer-related gene regulation
- Algal biology and biofuel production
- Autophagy in Disease and Therapy
Helmholtz Zentrum München
2016-2025
Target (Germany)
2023-2024
Technical University of Munich
2009-2023
Center for Integrated Protein Science Munich
2009-2021
Hospital Felício Rocho
2017
Max Planck Institute of Biochemistry
2016
Max Planck Society
2014
European Molecular Biology Laboratory
2010
European Molecular Biology Laboratory
2009
Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation1, has key role in organ injury, degenerative disease and vulnerability therapy-resistant cancers2. Although substantial progress been made understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic cell-intrinsic that determine sensitivity toward ferroptosis remain unknown. Here we show fully reduced forms vitamin K-a group naphthoquinones includes menaquinone...
Abstract Intraflagellar transport ( IFT ) relies on the complex and is required for ciliogenesis. The ‐B consists of 9–10 stably associated core subunits six “peripheral” that were shown to dissociate from structure at moderate salt concentration. We purified C hlamydomonas reinhardtii as recombinant proteins show they form a stable independently core. suggest nomenclature ‐B1 (core) ‐B2 (peripheral) two subcomplexes. demonstrate 88, together with N‐terminal domain 52, necessary bridge...
Ferroptosis is evolving as a highly promising approach to combat difficult-to-treat tumour entities including therapy-refractory and dedifferentiating cancers1-3. Recently, ferroptosis suppressor protein-1 (FSP1), along with extramitochondrial ubiquinone or exogenous vitamin K NAD(P)H/H+ an electron donor, has been identified the second ferroptosis-suppressing system, which efficiently prevents lipid peroxidation independently of cyst(e)ine-glutathione (GSH)-glutathione peroxidase 4 (GPX4)...
Large language models have greatly enhanced our ability to understand biology and chemistry, yet robust methods for structure-based drug discovery, quantum chemistry structural are still sparse. Precise biomolecule-ligand interaction datasets urgently needed large models. To address this, we present MISATO, a dataset that combines mechanical properties of small molecules associated molecular dynamics simulations ~20,000 experimental protein-ligand complexes with extensive validation data....
Abstract Dystonia is a rare-disease trait for which large-scale genomic investigations are still underrepresented. Genetic heterogeneity among patients with unexplained dystonia warrants interrogation of entire genome sequences, but this has not yet been systematically evaluated. To significantly enhance our understanding the genetic contribution to dystonia, we (re)analyzed 2,874 whole-exome sequencing (WES), 564 whole-genome (WGS), as well 80 fibroblast-derived proteomics datasets,...
Autophagy-driven nuclear transfer of miR-126-5p guided by Mex3a enables direct inhibition caspase-3 and protects against atherosclerosis.
The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort available vaccines, effective therapeutics are still missing to limit severe disease mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations co-crystal structure confirm that blocks the PLpro catalytic pocket in unexpected binding mode. We show drug inhibits viral replication at...
Cilia are ubiquitous eukaryotic organelles impotant for cellular motility, signaling, and sensory reception. Cilium formation requires intraflagellar transport of structural signaling components involves 22 different proteins organized into (IFT) complexes IFT-A IFT-B that transported by molecular motors. The complex constitutes the backbone polymeric IFT trains carrying cargo between cilium cell body. Currently, high-resolution structures only available smaller subcomplexes leaving > 50%...
Ferroptosis, marked by iron-dependent lipid peroxidation, may present an Achilles heel for the treatment of cancers. Ferroptosis suppressor protein-1 (FSP1), as second ferroptosis mainstay, efficiently prevents peroxidation via NAD(P)H-dependent reduction quinones. Because its molecular mechanisms have remained obscure, we studied numerous FSP1 mutations in cancer or identified untargeted random mutagenesis. This mutational analysis elucidates FAD/NAD(P)H-binding site and proton-transfer...
Ferroptosis, a regulated cell death hallmarked by unrestrained lipid peroxidation, plays pivotal role in the pathophysiology of various diseases, making it promising therapeutic target. Glutathione peroxidase 4 (GPX4) prevents ferroptosis reducing (phospho)lipid hydroperoxides, yet evaluation its actual activity has remained arduous. Here, we present tangible method using affinity-purified GPX4 to capture snapshot native activity. Next measuring activity, this improved allows for...
Histone post-translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role transcription. In this study, we characterize the an acylation on lateral surface octamer, H3K122 succinylation (H3K122succ), function and Using succinylated at vitro transcription assays, show that presence H3K122succ is sufficient to stimulate line with this, found our ChIP assays enriched promoters active...
Abstract The A-repeat region of the lncRNA Xist is critical for X inactivation and harbors several N6-methyladenosine (m6A) modifications. How m6A modification affects conformation conserved AUCG tetraloop hairpin A-repeats how it can be recognized by YTHDC1 reader protein unknown. Here, we report NMR solution structure (m6A)UCG hairpin, which reveals that base extends 5′ stacking A-form helical stem, resembling unmethylated tetraloop. A crystal bound to shows (m6A)UC nucleotides are YTH...
Abstract Coronaviruses modify their single-stranded RNA genome with a methylated cap during replication to mimic the eukaryotic mRNAs. The capping process is initiated by several nonstructural proteins (nsp) encoded in viral genome. methylation performed two methyltransferases, nsp14 and nsp16, while nsp10 acts as co-factor both. Additionally, carries an exonuclease domain which operates proofreading system of Both nsp16 were reported independently bind nsp10, but available structural...
A helminth larval extract and its component Hpb glutamate dehydrogenase induce an anti-inflammatory mediator switch to suppress type-2 inflammation.
Abstract The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is hallmark severe dysfunction obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue axis controls glucose homeostasis. We found liver primarily controlled circulating levels soluble FNDC4 (sFNDC4) lowering hepatokine led to prediabetes mice. Further, identified orphan adhesion...
Selenium-dependent glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, preventing unrestrained (phospho)lipid peroxidation by reducing phospholipid hydroperoxides (PLOOH). However, contribution other peroxidases in ferroptosis protection remains unclear. We show that cells lacking GPX4 still exhibit substantial PLOOH-reducing capacity, suggesting a alternative PLOOH peroxidases. By scrutinizing potential candidates, we found although overexpression peroxiredoxin 6 (PRDX6),...
Circular RNAs (circRNAs) are generated by back splicing of mostly mRNAs and gaining increasing attention as a novel class regulatory that control various cellular functions. However, their physiological roles functional conservation in vivo rarely addressed, given the inherent challenges genetic inactivation. Here, we aimed to identify locus conserved circRNAs mice humans, which can be genetically deleted due retained intronic elements not contained mRNA host gene eventually address...