A5023166699- Photosynthetic Processes and Mechanisms
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Viral-associated cancers and disorders
- Microbial Community Ecology and Physiology
- Bacterial Genetics and Biotechnology
- Cytomegalovirus and herpesvirus research
- Protist diversity and phylogeny
- Muscle Physiology and Disorders
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- Intensive Care Unit Cognitive Disorders
- Metalloenzymes and iron-sulfur proteins
- Algal biology and biofuel production
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Cyclization and Aryne Chemistry
- Lymphoma Diagnosis and Treatment
- Lipid Membrane Structure and Behavior
- Inflammasome and immune disorders
- RNA Interference and Gene Delivery
- Autophagy in Disease and Therapy
- Adenosine and Purinergic Signaling
- Origins and Evolution of Life
- Takotsubo Cardiomyopathy and Associated Phenomena
Max Planck Institute of Biophysics
2016-2025
Max Delbrück Center
2014-2024
Charité - Universitätsmedizin Berlin
2016-2024
University of Miami
2014
Bayer (Germany)
2012-2014
Goethe University Frankfurt
2009-2014
Max Planck Society
2014
Software (Germany)
2008-2014
Georgetown University Medical Center
2013
Georgetown University
2013
There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into best practices in the areas of sequence data generation, analysis, interpretation reporting. The CLARITY Challenge was designed spur convergence diagnosing genetic disease starting from case history data. DNA samples were obtained three families with heritable disorders genomic donated by platform vendors....
The chloroplast adenosine triphosphate (ATP) synthase uses the electrochemical proton gradient generated by photosynthesis to produce ATP, energy currency of all cells. Protons conducted through membrane-embedded Fo motor drive ATP synthesis in F1 head rotary catalysis. We determined high-resolution structure complete cF1Fo complex cryo-electron microscopy, resolving side chains 26 protein subunits, five nucleotides head, and pathway from rotor ring. flexible peripheral stalk redistributes...
Abstract Heat stress transcription factors (Hsfs) regulate gene expression in response to environmental stress. The Hsf network plants is controlled at the transcriptional level by cooperation of distinct members and interaction with chaperones. We found two general mechanisms regulation chaperones while analyzing three major Hsfs, A1, A2, B1, tomato (Solanum lycopersicum). First, Hsp70 Hsp90 function direct interactions. represses activity HsfA1, including its DNA binding, coactivator HsfB1...
We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by combination cryo-EM and X-ray crystallography. The final resolves 58 60 dimer subunits. Horizontal helices subunit in Fo wrap around c-ring rotor, total six vertical assigned to subunits a, b, f, i, 8 span membrane. Subunit (A6L human) is an evolutionary derivative bacterial b subunit. On lumenal membrane surface, f establishes direct contact between two monomers. Comparison...
Mitochondrial ATP synthases form dimers, which assemble into long ribbons at the rims of inner membrane cristae. We reconstituted detergent-purified mitochondrial synthase dimers from green algae Polytomella sp. and yeast Yarrowia lipolytica liposomes examined them by electron cryotomography. Tomographic volumes revealed that both species self-assemble rows bend lipid bilayer locally. The dimer induced degree curvature closely resemble those in Monomers do not visibly rows. No specific...
Abstract Background Sepsis and inflammation can cause intensive care unit‐acquired weakness (ICUAW). Increased interleukin‐6 (IL‐6) plasma levels are a risk factor for ICUAW. IL‐6 signalling involves the glycoprotein 130 (gp130) receptor JAK/STAT‐pathway, but its role in sepsis‐induced muscle wasting is uncertain. In clinical observational study, we found that target gene, SOCS3 , was increased skeletal of ICUAW patients indicative JAK/STAT‐pathway activation. We tested hypothesis...
Accumulation and infiltration of microglia/brain macrophages around into glioma tissue promote tumor invasion expansion. One tumor-promoting mechanism is upregulation membrane type 1 matrix metalloprotease (MT1-MMP), which promotes the degradation extracellular matrix. MT1-MMP induced by soluble factors released cells activating microglial Toll-like receptor 2 (TLR2). Versican identified proteomics was silenced in short interference RNA hairpin approaches studied vitro after injection mouse...
Hemes switch spots in a terminal oxidase Reduction of molecular oxygen to water is the driving force for respiration aerobic organisms and catalyzed by several distinct integral membrane complexes. These include an exclusively prokaryotic enzyme, cytochrome bd–type quinol oxidase, which potential antimicrobial target. Safarian et al. determined high-resolution cryo–electron microscopy structure this enzyme from enteric bacterium Escherichia coli . Comparison homolog reveals complete...
Background Diabetic nephropathy (DN) is a complex and chronic metabolic disease that evolves into progressive fibrosing renal disorder. Effective transcriptomic profiling of slowly evolving processes such as DN can be problematic. The changes occur are often subtle escape detection by conventional oligonucleotide DNA array analyses. Methodology/Principal Findings We examined microdissected human tissue with or without using Affymetrix microarrays (HG-U133A) standard Robust Multi-array...
The attachment, entry, and fusion of Kaposi's sarcoma-associated herpesvirus (KSHV) with target cells are mediated by complex machinery containing, among others, viral glycoprotein H (gH) its alleged chaperone, gL. We observed that KSHV gH, in contrast to homologues several other herpesviruses, is transported the cytoplasm membrane independently from gL, but not vice versa. Mutational analysis revealed N terminus gH sufficient for gL interaction. However, entire extracellular part required...
Kaposi's sarcoma-associated herpesvirus encodes four genes with homology to the family of interferon regulatory factors (IRFs). At least one these viral IRFs, vIRF-3, is expressed in latently herpesvirus-infected primary effusion lymphoma (PEL) cells and essential for survival PEL cells. We now report that vIRF-3 interacts cellular IRF-5, thereby inhibiting binding IRF-5 interferon-responsive promoter elements. Consequently, blocked IRF-5-mediated activation. A central double helix motif...
Somatic cells can be reprogrammed to induced pluripotent stem by over-expression of OCT4, SOX2, KLF4 and c-MYC (OSKM). With the aim unveiling early mechanisms underlying induction pluripotency, we have analyzed transcriptional profiles at 24, 48 72 hours post-transduction OSKM into human foreskin fibroblasts. Experiments confirmed that upon viral transduction, immediate response is innate immunity, which induces free radical generation, oxidative DNA damage, p53 activation, senescence,...
Critically ill patients frequently develop muscle atrophy and weakness in the intensive-care-unit setting [intensive care unit-acquired (ICUAW)]. Sepsis, systemic inflammation, acute-phase response are major risk factors. We reported earlier that protein serum amyloid A1 (SAA1) is increased accumulates of ICUAW patients, but its relevance was unknown. Our objectives were to identify SAA1 receptors their downstream signalling pathways myocytes skeletal investigate role inflammation-induced...
Abstract The nicotinamide adenine dinucleotide phosphate (NADPH) dehydrogenase (NDH) complex is crucial for photosynthetic cyclic electron flow and respiration, transferring electrons from ferredoxin to plastoquinone while transporting H + across the chloroplast membrane. This process boosts adenosine triphosphate production, regardless of NADPH levels. In flowering plants, NDH forms a supercomplex with photosystem I, enhancing its stability under high light. We report cryo-electron...
Cellular Ephrin receptor tyrosine kinases (Ephrin receptors, Ephs) were found to interact efficiently with the gH/gL glycoprotein complex of rhesus monkey rhadinovirus (RRV). Since EphA2 was recently identified as a for Kaposi's sarcoma-associated herpesvirus (KSHV) (Hahn et al., Nature Medicine 2012), we analyzed RRV and KSHV in parallel respect Eph-binding Eph-dependent entry. Ten 14 Eph proteins, including both A- B-type, interacted gH/gL. Two strains markedly different sequences...
Summary Iron uptake in Gram‐negative bacteria involves four distinct steps: (i) siderophore synthesis, (ii) secretion into the extracellular space, (iii) iron chelation by siderophores, and (iv) siderophore/iron via complexes outer membrane intermembrane space as well plasma membrane. This process is characterized for some proteobacterial systems, but largely unexplored scarcely investigated cyanobacteria such heterocyst‐forming cyanobacterium Anabaena sp. PCC 7120. Two putative synthesis...
The ephrin receptor tyrosine kinase A2 (EphA2) is an entry for Kaposi's sarcoma-associated herpesvirus (KSHV) that engaged by the virus through its gH/gL glycoprotein complex. We describe here natural ligands inhibit gH/gL-EphA2 interaction. effects of point mutations within EphA2 demonstrated KSHV interacts with a restricted set same residues mediate binding A-type ephrins. Two previously described inhibitors interaction A5 also inhibited to EphA2. more potent two compounds infection blood...
Native polyacrylamide gel electrophoresis (PAGE) is an important technique for the analysis of membrane protein complexes. A major breakthrough was development blue native (BN-) and high resolution clear (hrCN-) PAGE techniques. Although these techniques are very powerful, they could not be applied to all systems with same resolution. We have developed alternative protocol complexes plant chloroplasts cyanobacteria, which we termed histidine- deoxycholate-based (HDN-) PAGE. compared capacity...
The role of TolC has largely been explored in proteobacteria, where it functions as a metabolite and protein exporter. In contrast, little research carried out on the function cyanobacterial homologues, consequence, not much is known about mechanism antibiotic uptake secretion general. It suggested that TolC-like homologue filamentous, heterocyst-forming cyanobacterium Anabaena sp. PCC 7120, termed heterocyst glycolipid deposition D (HgdD), involved both lipid secretion. To describe its...