A5053004770- Genetics, Aging, and Longevity in Model Organisms
- Alzheimer's disease research and treatments
- Circadian rhythm and melatonin
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Cholinesterase and Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- Heat shock proteins research
- Prion Diseases and Protein Misfolding
- FOXO transcription factor regulation
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- PI3K/AKT/mTOR signaling in cancer
- Liver Diseases and Immunity
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Protist diversity and phylogeny
- Pluripotent Stem Cells Research
- Evolution and Genetic Dynamics
- Physiological and biochemical adaptations
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
- Drug Transport and Resistance Mechanisms
University of Freiburg
2015-2024
University Medical Center Freiburg
2018
Institute of Molecular Biology
2014
Mosaiques Diagnostics and Therapeutics (Germany)
2011
Lifenet Health
2010
Institut thématique Génétique, génomique et bioinformatique
2006-2010
Center for Systems Biology
2009
Ludwig-Maximilians-Universität München
1998-2006
Heidelberg University
2000
Boehringer Ingelheim (Germany)
2000
To optimize their growth and survival, plants perceive respond to ultraviolet-B (UV-B) radiation. However, neither the molecular identity of UV-B photoreceptor nor photoperception mechanism is known. Here we show that dimers UVR8 protein UV-B, probably by a tryptophan-based mechanism. Absorption induces instant monomerization interaction with COP1, central regulator light signaling. Thereby this signaling cascade controlled mediates photomorphogenic responses securing plant acclimation thus...
Neutrophils communicate with each other to form swarms in infected organs. Coordination of this population response is critical for the elimination bacteria and fungi. Using transgenic mice, we found that neutrophils have evolved an intrinsic mechanism self-limit swarming avoid uncontrolled aggregation during inflammation. G protein-coupled receptor (GPCR) desensitization acts as a negative feedback control stop migration when they sense high concentrations self-secreted attractants...
Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface lysosomes. They act in a non-redundant manner to anchor tuberous sclerosis complex (TSC) protein lysosomes suppress activation metabolic master regulator mechanistic target rapamycin (mTORC1) by amino acids insulin. Like TSC complex, G3BP1 deficiency elicits phenotypes related mTORC1...
Presenilin-1 (PS1) facilitates γ-secretase cleavage of the β-amyloid precursor protein and intramembraneous Notch1. Although Alzheimer's disease-associated mutations in homologous presenilin (PS2) gene elevate amyloid β-peptide (Aβ42) production like PS1 mutations, here we demonstrate that a ablation PS2 (unlike PS1) mice does not result severe phenotype resembling Notch-ablated animals. To investigate amyloidogenic function more directly, mutagenized conserved aspartate at position 366 to...
The majority of cases with familial Alzheimer’s disease (FAD) are linked to mutations the presenilin (PS) genes. These genes show considerable sequence similarity sel‐12 gene Caenorhabditis elegans , which has been postulated function in facilitated signalling by lin‐12 and glp‐1 . In order analyse functional conservation presenilins, we introduced human PS‐1 cDNA, as well clinical deletion mutant proteins, into animals tested their potential rescue egg‐laying defect. Human expressed from...
Upon perception of a noxious stimulus, an organism executes defense mechanisms, such as escape responses. The molecular basis these mechanisms is poorly understood. In this paper we show that upon exposure to temperature, Caenorhabditis elegans reacts by withdrawal reflex. To analyze thermal avoidance behavior, developed laser-based assay quantify the response. reflex can be observed in 98% adult animals, but not executed animals diapause. response differs significantly from thermotaxis...
Mutations in two genes encoding the putative kinases LRRK2 and PINK1 have been associated with inherited variants of Parkinson disease. The physiological role both proteins is not known at present, but studies model organisms linked their mutants to distinct aspects mitochondrial dysfunction, increased vulnerability oxidative endoplasmic reticulum stress, intracellular protein sorting. Here, we show that a mutation Caenorhabditits elegans homologue PTEN-induced kinase pink-1 gene resulted...
The neurotoxin MPTP and its active metabolite MPP<sup>+</sup> cause Parkinson’s disease (PD)-like symptoms in vertebrates by selectively destroying dopaminergic neurons the substantia nigra. MPTP/MPP<sup>+</sup> models have been established rodents to screen for pharmacologically compounds. In addition being costly time consuming, these animal are not suitable large scale testings using compound libraries. We present a novel MPP<sup>+</sup>-based model...
Increased Tau protein amyloidogenicity has been causatively implicated in several neurodegenerative diseases, collectively called tauopathies. In pathological conditions, becomes hyperphosphorylated and forms intracellular aggregates. The deletion of K280, which is a mutation that commonly appears patients with frontotemporal dementia Parkinsonism linked to chromosome 17, enhances aggregation propensity (pro-aggregation). contrast, introduction the I277P I308P mutations prevents β-sheet...
Disturbance of cellular functions results in the activation stress-signaling pathways that aim at restoring homeostasis. We performed a genome-wide screen to identify components signal transduction mitochondrial unfolded protein response (UPRmt) nuclear chaperone promoter. used ROS generating complex I inhibitor paraquat induce UPRmt, and we employed RNAi exposure post-embryonically allow testing genes whose knockdown embryonic lethality. identified 54 novel regulators ROS–induced UPRmt....
Abstract Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. used capillary electrophoresis mass spectrometry (CE-MS) identify disease-specific peptide patterns choledocholithiasis (n = 16), PSC 18), 16) training set. A model for...
The kinase mammalian target of rapamycin (mTOR) exists in two multiprotein complexes (mTORC1 and mTORC2) is a central regulator growth metabolism. Insulin activation mTORC1, mediated by phosphoinositide 3-kinase (PI3K), Akt, the inhibitory tuberous sclerosis complex 1/2 (TSC1-TSC2), initiates negative feedback loop that ultimately inhibits PI3K. We present data-driven dynamic insulin-mTOR network model integrates entire core used this to investigate less well understood mechanisms which...
The mammalian intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides from gut lumen into epithelial cells acts in parallel with amino acid transporters. Here we address importance orthologue PEP-2 for assimilation dietary protein overall nutrition Caenorhabditis elegans. pep-2 is expressed specifically along apical membrane cells, deletion mutant animals, intact peptides abolished. consequences are a severely retarded development, reduced progeny body size, increased...
Background Any organism depends on its ability to sense temperature and avoid noxious heat. The nematode Caenorhabditis elegans responds temperatures exceeding ∼35°C also senses changes in environmental the range between 15 25°C. neural circuits molecular mechanisms involved thermotaxis have been successfully studied, whereas details of thermal avoidance behavior remain elusive. In this work, we investigate neurological aspects thermonociception using genetic, cell biological physiological...
Mechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase (PLK1) are major drivers cancer cell growth proliferation, inhibitors both protein kinases currently being investigated in clinical studies. To date, MTORC1's PLK1's functions mostly studied separately, reports on their mutual crosstalk scarce. Here, we identify PLK1 as a physical MTORC1 interactor human cells. inhibition enhances activity under nutrient sufficiency starved cells, directly phosphorylates the component...
Autophagy is stimulated by stress conditions and needs to be precisely tuned ensure cellular homeostasis organismal development health. The kinase mechanistic target of rapamycin (mTOR) forms the enzymatic core highly conserved mTOR complexes mTORC1 mTORC2. a key inhibitor autophagy, yet function mTORC2 in autophagy controversial. We here show that inactivation its direct serum- glucocorticoid-inducible 1 (SGK-1) potently induces autophagic degradation mitochondria C. elegans. Enhanced...
Retromer is an evolutionarily conserved multiprotein complex that orchestrates the endocytic recycling of integral membrane proteins. Here, we demonstrate retromer also required to maintain lysosomal amino acid signaling through mTORC1 across species. Without retromer, acids no longer stimulate translocation membrane, which leads a loss activity and increased induction autophagy. Mechanistically, show its effect on not linked retromer's role in transmembrane Instead, cooperates with RAB7-GAP...