A5082089142- Nuclear Structure and Function
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- Genetics, Aging, and Longevity in Model Organisms
- Microbial Metabolic Engineering and Bioproduction
- DNA Repair Mechanisms
- Bioinformatics and Genomic Networks
- Microtubule and mitosis dynamics
- Metabolomics and Mass Spectrometry Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Chemical Sensor Technologies
- Nutrition, Genetics, and Disease
- Amino Acid Enzymes and Metabolism
- Biofield Effects and Biophysics
- RNA and protein synthesis mechanisms
- CAR-T cell therapy research
- Analytical Chemistry and Chromatography
- Immunotherapy and Immune Responses
- Biomedical Text Mining and Ontologies
- RNA regulation and disease
- RNA modifications and cancer
AstraZeneca (Netherlands)
2025
ETH Zurich
2017-2024
University of Groningen
2009-2019
Biotechnology Institute
2012-2019
European Research Council
2017
Dialyse Centrum Groningen
2012
Netherlands Metabolomics Centre
2012
Institute of Molecular Life Sciences
2010
An integrated account of the molecular changes occurring during process cellular aging is crucial towards understanding underlying mechanisms. Here, using novel culturing and computational methods as well latest analytical techniques, we mapped proteome transcriptome replicative lifespan budding yeast. With age, found primarily proteins involved in protein biogenesis to increase relative their transcript levels. Exploiting dynamic nature our data, reconstructed high-level directional...
Natively unfolded linkers facilitate nuclear membrane protein import.
The basket of the nuclear pore complex (NPC) is generally depicted as a discrete structure eight protein filaments that protrude into nucleoplasm and converge in ring distal to NPC. We show yeast proteins Mlp1p Mlp2p are necessary components they also embed NPC within dynamic network, whose extended interactome includes spindle organizer, silencing factors, proteasome, key messenger ribonucleoproteins (mRNPs). Ultrastructural observations indicate reduces chromatin crowding around central...
The identification of unknown compounds remains to be a bottleneck mass spectrometry (MS)-based metabolomics screening experiments. Here, we present novel approach which facilitates the and quantification analytes containing aldehyde ketone groups in biological samples by adding chemical information MS data. Our strategy is based on rapid autosampler-in-needle-derivatization with p-toluenesulfonylhydrazine (TSH). resulting TSH-hydrazones are separated ultrahigh-performance liquid...
A comprehensive description of the phenotypic changes during cellular aging is key towards unraveling its causal forces. Previously, we mapped age-related in proteome and transcriptome (Janssens et al., 2015). Here, employing same experimental procedure model-based inference, generate a account metabolic replicative life Saccharomyces cerevisiae. With age, found decreasing metabolite levels, growth substrate uptake rates accompanied by switch from aerobic fermentation to respiration, with...
The nuclear pore complex (NPC) mediates nearly all exchanges between nucleus and cytoplasm, in many species, it changes composition as the organism ages. However, how these arise whether they contribute themselves to ageing is poorly understood. We show that SAGA-dependent attachment of DNA circles NPCs replicatively yeast cells causes lose their basket cytoplasmic complexes. These were not recognized defective by NPC quality control machinery (SINC) targeted ESCRTs. They interacted normally...
In many organisms, aging is a clear risk factor for increased rates of chromosome mis-segregation, the main source aneuploidy. Here, we report that old yeast mother cells lose chromosomes by partitioning them asymmetrically to their daughter together with pre-existing (old) Sindle Pole Body (centrosome equivalent in yeast). Strikingly, remodelling NPC and displacement its nuclear basket triggered these asymmetric segregation events. Concomitantly, also caused unspliced pre-mRNAs leak...
In many organisms, aging is a clear risk factor for increased rates of chromosome mis-segregation, the main source aneuploidy. Here, we report that old yeast mother cells lose chromosomes by partitioning them asymmetrically to their daughter together with pre-existing (old) Sindle Pole Body (centrosome equivalent in yeast). Strikingly, remodelling NPC and displacement its nuclear basket triggered these asymmetric segregation events. Concomitantly, also caused unspliced pre-mRNAs leak...
Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably melanoma. However, its wider application efficacy has been restricted by the limited accessibility, proliferative capacity effector function tumor-specific TIL. Here, we develop platform for efficient identification TCR genes from diagnostic biopsies, core-needle biopsies frozen non-viable format, to enable...
Nuclear transport of the Saccharomyces cerevisiae membrane proteins Src1/Heh1 and Heh2 across NPC is facilitated by a long intrinsically disordered linker between nuclear localization signal (NLS) transmembrane domain. The import reporter derived from dependent on FG-Nups in central channel, can position factor-bound NLS vicinity while segment resides pore membrane. Here, we present quantitative analysis karyopherin-mediated passive efflux Heh2, including data mobility different...
Although individuals of many species inexorably age, a number observations established that the rate aging is modulated in response to variety mild stresses. Here, we investigated how heat stress promotes longevity yeast. We show upon growth at higher temperature, yeast cells relax retention DNA circles, which act as factors mother cell. The enhanced frequency circles redistribute daughter was not due changes anaphase duration or nuclear shape but solely downregulation diffusion barrier...
The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using silico means. A particular focus ontologies, because these are a key technology systematically integrate heterogeneous information about process. Related topics were databases data integration. Other talks tackled modeling issues applications, latter including focused marker development cellular stress as well diseases, diseases of kidney skin.
ABSTRACT In many organisms, aging is a clear risk factor for increased rates of chromosome mis-segregation, the main source aneuploidy. Here, we report that old yeast mother cells lose chromosomes by partitioning them asymmetrically to their daughter together with pre-existing (old) Sindle Pole Body (centrosome equivalent in yeast). Strikingly, remodelling NPC and displacement its nuclear basket triggered these asymmetric segregation events. Concomitantly, also caused unspliced pre-mRNAs...
Proteostasis decline, mitochondrial dysfunction, chromatin changes and nuclear envelope alteration are all cellular hallmarks of aging. However, how these defects arise, influence each other lead to death is unclear. Here, we show that anchorage accumulating DNA circles pore complexes (NPCs) in old yeast cells displaces the basket from NPCs impairs surveillance machinery restricts pre-mRNA export increases intron retention. This caused aberrant translation formation protein aggregates....
The nuclear pore complex (NPC) mediates nearly all exchanges between nucleus and cytoplasm, changes composition in many species as the organism ages. However, how these arise whether they contribute themselves to aging is poorly understood. We show that replicatively yeast cells attachment of DNA circles NPCs drives displacement NPCs’ basket cytoplasmic complexes. Remodeling NPC resulted from regulation components by SAGA, rather than damages. These affected interaction with mRNA export...
Multiple mechanisms are in place to regulate adequate synthesis of proteins, ranging from ways ensure sequence fidelity, polypeptide folding and protein modification, control amounts subcellular localization the molecules. Some these act at level mRNA export targeting. nuclear consists three coupled consecutive steps: (1) packaging into messenger ribonucleoprotein (mRNP); (2) transport through pore complexes (NPCs); (3) directional release cytoplasm (for a review see refs. 1-2). The...
A comprehensive description of the phenotypic changes during cellular aging is key towards unraveling its causal forces. Using recently developed experimental tools, which previously had enabled us to map age related in proteome and transcriptome (Janssens et al., 2015), model-based inference methods, here, we generated a account metabolic entire replicative life Saecharomyces cerevisiae. With age, found decreasing metabolite levels, growth substrate uptake rates accompanied by switch from...