A5076217749- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Circadian rhythm and melatonin
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Reproductive Biology and Fertility
- Microtubule and mitosis dynamics
- Heat shock proteins research
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Fungal and yeast genetics research
- Genomics and Chromatin Dynamics
- Photosynthetic Processes and Mechanisms
- interferon and immune responses
- Renal and related cancers
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Physiological and biochemical adaptations
- Bioenergy crop production and management
- Lipid metabolism and biosynthesis
- Spaceflight effects on biology
- Plant nutrient uptake and metabolism
University of Oslo
2018-2024
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2018-2022
Friedrich Miescher Institute
2010-2021
Howard Hughes Medical Institute
2004-2006
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2006
University of Washington
2006
Fred Hutch Cancer Center
2004
Research Institute of Molecular Pathology
1997-2000
University of Dundee
1998
European Molecular Biology Laboratory
1998
Sister chromatid cohesion is crucial for chromosome segregation during mitosis. Loss of very possibly triggers sister separation at the metaphase --> anaphase transition. This process depends on destruction inhibitory proteins like Pds1p (Cut2p), which thought to liberate a sister-separating protein Esp1p (Cut1p). By looking mutants that separate centromeres in presence Pds1p, this and previous study have identified six essential establishing or maintaining cohesion. Four these proteins,...
Entry into anaphase and exit from mitosis depend on a ubiquitin-protein ligase complex called the anaphase-promoting (APC) or cyclosome. At least 12 different subunits were detected in purified particle budding yeast, including previously identified proteins Apc1p, Cdc16p, Cdc23p, Cdc26p, Cdc27p. Five additional low nanogram amounts by tandem mass spectrometric sequencing. Apc2p, Apc5p, RING-finger protein Apc11p are conserved yeast to humans. Apc2p is similar cullin Cdc53p, which subunit of...
The molecular mechanisms that maintain totipotency of the germline are not well understood. Here, we show two conserved translational regulators, MEX-3 and GLD-1, essential for maintaining in Caenorhabditis elegans germline. In mex-3 gld-1 mutants, germ cells transdifferentiate into various somatic cell types such as muscles or neurons. Our findings implicate RNA regulation maintenance totipotency, suggest multiple at different stages development, establish a genetically tractable model...
Human ataxin 2 is a protein of unknown function that implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. We found C. elegans ortholog 2, ATX-2, forms complex with PAB-1, cytoplasmic polyA-binding protein, and ATX-2 required for development germline. In absence proliferation stem cells reduced, germline abnormally masculinized. These defects appear to result from inappropriate translational regulation normally mediated by conserved KH-domain GLD-1. find MEX-3, second...
The mechanisms controlling cell fate determination and reprogramming are fundamental for development. A profound reprogramming, allowing the production of pluripotent cells in early embryos, takes place during oocyte-to-embryo transition. To understand how oocyte potential is controlled, we sought Caenorhabditis elegans mutants which embryonic transcription initiated precociously germ cells. This screen identified LIN-41, a TRIM-NHL protein component somatic heterochronic pathway, as...
Preferably, lifespan-extending therapies should work when applied late in life without causing undesired pathologies. Reducing insulin/insulin-like growth factor (IGF)-1 signaling (IIS) increases lifespan across species, but the effects of reduced IIS interventions extreme geriatric ages remains unknown. Using nematode Caenorhabditis elegans, we engineered conditional depletion DAF-2/insulin/IGF-1 transmembrane receptor using an auxin-inducible degradation (AID) system. This allowed for...
Histone H3 Lys 4 methylation (H3K4me) is deposited by the conserved SET1/MLL methyltransferases acting in multiprotein complexes, including Ash2 and Wdr5. Although individual subunits contribute to complex activity, how they influence gene expression specific tissues remains largely unknown. In Caenorhabditis elegans, SET-2/SET1, WDR-5.1, ASH-2 are differentially required for germline H3K4 methylation. Using profiling on germlines from animals lacking set-2, ash-2, or wdr-5.1, we show that...
Precise genome editing by the Cas9 nuclease depends on exogenously provided templates for homologous recombination. Here, we compare oligonucleotides with short homology and circular DNA molecules extensive to genomic targets as homology-based repair of CRISPR/Cas9 induced double-strand breaks. We find be choice introducing small sequence changes into based efficiency ease use. show that polarity oligonucleotide greatly affects efficiency: in sense orientation respect target gene are better...
The four-cell C. elegans embryo contains two sister cells called ABa and ABp that initially have equivalent abilities to produce ectodermal cell types. Multiple Notch-mediated interactions occur during the early divisions diversify descendants. first interaction determines pattern of types produced by ABp. second induces granddaughters become mesodermal precursors. We show T-box transcription factors TBX-37 TBX-38 are essential for induction, these expressed in ABa, but not ABp, provide...
Translational repression is often accompanied by mRNA degradation. In contrast, many mRNAs in germ cells and neurons are "stored" the cytoplasm a repressed but stable form. Unlike repression, stabilization of these surprisingly little understood. A key player Caenorhabditis elegans cell development STAR domain protein GLD-1. By genome-wide analysis regulation line, we observed that GLD-1 has widespread role repressing translation but, importantly, also stabilizing sub-population its targets....
The cold shock domain is one of the most highly conserved motifs between bacteria and higher eukaryotes. Y-box-binding proteins represent a subfamily with pleiotropic functions, ranging from transcription in nucleus to translation cytoplasm. These have been investigated all major model organisms except Caenorhabditis elegans. In this study, we set out fill gap present functional characterization CEYs, C. elegans proteins. We find that, similar other organisms, CEYs are essential for proper...
RNA-binding proteins regulate all aspects of RNA metabolism. Their association with is mediated by domains, which many remain uncharacterized. A recently reported example the NHL domain, found in prominent regulators cellular plasticity like C. elegans LIN-41. Here we employ an integrative approach to dissect specificity Using computational analysis, structural biology, and vivo studies worms human cells, find that a positively charged pocket, specific domain LIN-41 its homologs...
Cell-fate reprograming is at the heart of development, yet very little known about molecular mechanisms promoting or inhibiting in intact organisms. In C. elegans germline, germ cells into somatic requires chromatin perturbation. Here, we describe that such facilitated by GLP-1/Notch signaling pathway. This surprising, since this pathway best for maintaining undifferentiated germline stem cells/progenitors. Through a combination genetics, tissue-specific transcriptome analysis, and...
The ubiquitin-proteolytic system controls the stability of proteins in space and time. In this study, using a temperature-sensitive mutant allele cul-2 gene, we show that CRL2LRR-1 (CUL-2 RING E3 ubiquitin-ligase Leucine Rich Repeat 1 substrate recognition subunit) acts at multiple levels to control germline development. promotes germ cell proliferation by counteracting DNA replication ATL-1 checkpoint pathway. also participates mitotic proliferation/meiotic entry decision, presumably...
How animals rewire cellular programs to survive cold is a fascinating problem with potential biomedical implications, ranging from emergency medicine space travel. Studying hibernation-like response in the free-living nematode Caenorhabditis elegans, we uncovered regulatory axis that enhances natural resistance of nematodes severe cold. This involves conserved transcription factors, DAF-16/FoxO and PQM-1, which jointly promote survival by upregulating FTN-1, protein related mammalian...