A5087206685- Cell death mechanisms and regulation
- Immune Response and Inflammation
- interferon and immune responses
- NF-κB Signaling Pathways
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Inflammasome and immune disorders
- Autophagy in Disease and Therapy
- Escherichia coli research studies
- ATP Synthase and ATPases Research
- Viral gastroenteritis research and epidemiology
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Poxvirus research and outbreaks
- Acute Myeloid Leukemia Research
- Clostridium difficile and Clostridium perfringens research
- Immune Cell Function and Interaction
- Bacterial Genetics and Biotechnology
- Fungal and yeast genetics research
- Phagocytosis and Immune Regulation
- Enzyme Structure and Function
- Immune cells in cancer
- Animal Virus Infections Studies
- Cytokine Signaling Pathways and Interactions
- RNA regulation and disease
Institute of Medical Microbiology and Hygiene
2012-2025
University of Freiburg
2017-2025
University Medical Center
2025
University Medical Center Freiburg
2011-2023
La Trobe University
2009-2016
Czech Academy of Sciences, Institute of Microbiology
2013
Piaggio (Italy)
2009
The University of Melbourne
2003-2007
Walter and Eliza Hall Institute of Medical Research
2004
Integral proteins in the outer membrane of mitochondria control all aspects organelle biogenesis, being required for protein import, mitochondrial fission, and, metazoans, programmed cell death. How these integral are assembled had been unclear. In bacteria, Omp85 is an essential component insertion machinery, and we show that members family also found eukaryotes ranging from plants to humans. eukaryotes, present membrane. The gene encoding viability yeast, conditional omp85 mutants have...
Tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2) binds to cIAP1 and cIAP2 (cIAP1/2) recruits them the cytoplasmic domain of several members TNF receptor (TNFR) superfamily, including TNF-TNFR1 ligand-receptor complex. Here, we define a cIAP1/2-interacting motif (CIM) within TRAF-N TRAF2, use TRAF2 CIM mutants determine role cIAP1/2 individually, TRAF2-cIAP1/2 interaction, in TNFR1-dependent signaling. We show that both RING are required regulate NF-κB-inducing kinase...
The cell wall is essential for viability of fungi and an effective drug target in pathogens such as Candida albicans. contribution post-transcriptional gene regulators to integrity C. albicans unknown. We show that the Ccr4-Pop2 mRNA deadenylase, a regulator stability translation, required integrity. ccr4/pop2 mutants display reduced β-glucans sensitivity echinocandin caspofungin. Moreover, deadenylase are compromised filamentation virulence. demonstrate defective walls linked dysfunctional...
RIPK1 is involved in signaling from TNF and TLR family receptors. After receptor ligation, not only modulates activation of both canonical NIK-dependent NF-κB, but also regulates caspase-8 cell death. Although overexpression can cause caspase-8-dependent death, when RIPK1(-/-) cells are exposed to low doses cycloheximide, they die more readily than wild-type cells, indicating has pro-survival as well pro-apoptotic activities. To determine how promotes survival, we compared treated with TNF....
Proteins with N-terminal cysteine can undergo native chemical ligation and are useful for site-specific labeling or protein semisynthesis. Recombinant production of these has usually been by cleavage a precursor fusion at an internal residue. Here we describe simpler route to producing proteins. Overexpression in E. coli several proteins containing as the second amino acid residue yielded products which intiating methionine had completely cleaved endogenous aminopeptidase. While secondary...
DIABLO/Smac is a mitochondrial protein that can promote apoptosis by promoting the release and activation of caspases. To do so, must first be processed protease then released into cytosol, we show this in an intact cellular system. We propose precursor form enters mitochondria through stop-transfer pathway to its active inner membrane peptidase (IMP) complex. Catalytic subunits mammalian IMP complex were identified based on sequence conservation functional complementation, novel motif...
The mitochondrial inner and outer membranes are composed of a variety integral membrane proteins, assembled into the posttranslationally. small translocase (TIMs) group ∼10 kDa proteins that function as chaperones to ferry imported across intermembrane space membranes. In yeast, there 5 TIM proteins: Tim8, Tim9, Tim10, Tim12, Tim13, with equivalent reported in humans. Using hidden Markov models, we find many eukaryotes have Tim8 Tim13 Tim9 Tim10 subunits. Some provide "snapshots" evolution,...
Abstract Apoptosis acts in defense against microbial infection, and many infectious agents have developed strategies to inhibit host cell apoptosis. The human pathogen Chlamydia trachomatis ( Ctr ) is an obligate intracellular bacterium that strongly inhibits mitochondrial apoptosis of its but there no agreement how the bacteria achieve this. We here provide a molecular analysis chlamydial apoptosis-inhibition infected cells demonstrate block occurs during activation effectors apoptosis, Bak...
Abstract Mitochondria react to infection with sub-lethal signals in the apoptosis pathway. Mitochondrial can be inflammatory but mechanisms are only partially understood. We show that activation of caspase-activated DNase (CAD) mediates mitochondrial pro-inflammatory functions and substantially contributes host defense against viral infection. In cells lacking CAD, activity was reduced. Experimental CAD caused transient DNA-damage a pronounced DNA damage response, involving major kinase...
Caspases-9, -3 and -7 are activated in the mitochondrial apoptosis pathway lead to apoptotic phenotype. Caspases also function limit inflammation upon permeabilization through degradation of signalling proteins cGAS, MAVS IRF3. Cells mice lacking caspases have higher interferon levels resistant viral infection. We report that unstimulated, non-apoptotic cells caspase-3 functions cleave specifically very likely cGAS. In unstimulated HeLa cells, constitutive caspase-9- -3- but not 7-dependent...
Mitochondria evolved from a bacterial endosymbiont ancestor in which the integral outer membrane proteins would have been β‐barrel structured within plane of membrane. Initial proteomics on yeast mitochondria suggest that while most protein components are membrane, these mitochondrial behave as if they α‐helical transmembrane domains, rather than β‐barrels. These usually predicted to single segment at either N‐ or C‐terminus, however, more complex topologies also seen. We purified novel Om14...
Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, well TNF Receptor Superfamily members. Loss XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's disease. also caused by mutations the gene encoding NOD2 but mechanisms behind development deficient-patients are still unknown. Numerous other causing Disease occur genes controlling various...
The formation of amyloid‐like protein structures has recently emerged as a feature in signal transduction, particularly innate immunity. These appear to depend on defined domains for their but likely also require dedicated ways terminate signalling. We, here, define the immunity protein/Toll‐like receptor adaptor TIR‐domain‐containing adapter‐inducing interferon‐β ( TRIF ) novel platform fibril and probe initiation through well its termination Toll‐like 3 TLR 3)‐stimulated melanoma cells. A...
Chlamydia trachomatis is an obligate intracellular bacterial pathogen of medical importance. C. develops inside a membranous vacuole in the cytosol epithelial cells but manipulates host cell numerous ways. One prominent effect chlamydial infection inhibition apoptosis cell, molecular aspects this are unclear. Tumour necrosis factor (TNF) cytokine with important roles immunity, which produced by immune and can have pro-apoptotic non-apoptotic signalling activity. We here analysed through TNF...
Mitochondria were derived from intracellular bacteria and the mitochondrial intermembrane space is topologically equivalent to bacterial periplasm. Both compartments contain ATP-independent chaperones involved in transport of hydrophobic membrane proteins. The TIM (translocase inner membrane) 10 complex periplasmic chaperone SurA examined terms evolutionary relation, structural similarity, substrate binding specificity their function transporting polypeptides for insertion into membranes....
The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how viruses is shaped the remains incompletely understood. Past reports have indicated that bacteria may either promote or repress rotavirus replication in small intestine of mice. We now report replicated more efficiently intestines germ-free and antibiotic-treated mice compared animals with an unmodified microbiota. Antibiotic treatment also facilitated type I III...
Abstract Death receptors are transmembrane proteins that can induce the activation of caspase-8 upon ligand binding, initiating apoptosis. Recent work has highlighted great molecular complexity death receptor signalling, in particular through ubiquitination/deubiquitination. We have earlier defined deubiquitinase Ubiquitin-Specific Protease 27x (Usp27x) as an enzyme capable stabilizing pro-apoptotic Bcl-2 family member Bim. Here, we report enhanced expression Usp27x human melanoma cells...
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a "death ligand"—a member of the TNF superfamily that binds to receptors bearing death domains. As well causing apoptosis certain types tumor cells, TRAIL can activate both NF-κB and JNK signalling pathways. To determine role TGF-β-Activated Kinase-1 (TAK1) in signalling, we analyzed effects adding mouse embryonic fibroblasts (MEFs) derived from TAK1 conditional knockout mice. TAK1−/− MEFs were significantly...
Apoptosis mediated by Bax or Bak is usually thought to be triggered BH3-only members of the Bcl-2 protein family. proteins can directly bind and activate Bak, indirectly them binding anti-apoptotic family members, thereby relieving their inhibition Bak. Here we describe a third way activation Bax/Bak dependent apoptosis that does not require triggering multiple proteins. In factor myeloid (FDM) cell lines, cycloheximide induced mechanism, because Bax-/-Bak-/- lines were profoundly resistant,...