A5015732937- Epigenetics and DNA Methylation
- Fungal and yeast genetics research
- RNA modifications and cancer
- Cancer therapeutics and mechanisms
- Autoimmune and Inflammatory Disorders Research
- Genomics and Chromatin Dynamics
- Inflammasome and immune disorders
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Bacterial Genetics and Biotechnology
- Cancer Genomics and Diagnostics
- Rheumatoid Arthritis Research and Therapies
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- DNA and Nucleic Acid Chemistry
- Molecular Biology Techniques and Applications
- Spondyloarthritis Studies and Treatments
- Estrogen and related hormone effects
- CRISPR and Genetic Engineering
- Plant nutrient uptake and metabolism
- Immune Cell Function and Interaction
- Macrophage Migration Inhibitory Factor
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Protease and Inhibitor Mechanisms
- Kawasaki Disease and Coronary Complications
Novartis (Switzerland)
2004-2023
Novartis Institutes for BioMedical Research
2004-2017
Scripps Research Institute
2005
University of Basel
1994-2002
ETH Zurich
1996
An important recent advance in the functional analysis of Saccharomyces cerevisiae genes is development one-step PCR-mediated technique for deletion and modification chromosomal genes. This method allows very rapid gene manipulations without requiring plasmid clones interest. We describe here a new set plasmids that serve as templates PCR synthesis fragments allow variety modifications. Using selectable marker S. TRP1 or modules containing heterologous Schizosaccharomyces pombe his5+...
Abstract We have constructed and tested a dominant resistance module, for selection of S. cerevisiae transformants, which entirely consists heterologous DNA. This kanMX module contains the known kanr open reading‐frame E. coli transposon Tn 903 fused to transcriptional translational control sequences TEF gene filamentous fungus Ashbya gossypii. hybrid permits efficient transformants resistant against geneticin (G418). also lacZMT reporter in lacZ (lacking first 9 codons) is at its 3′ end...
We have fused the open reading frames of his3-complementing genes from Saccharomyces kluyveri and Schizosaccharomyces pombe to strong TEF gene promotor filamentous fungus Ashbya gossypii. Both chimeric modules cognate S. HIS3 were tested in transformations his3 cerevisiae strains using PCR fragments flanked by 40 bp target guide sequences. The 1·4 kb Sz. module (HIS3MX6) performed best. With less than 5% incorrectly targeted transformants, it functions as reliably widely used geniticin...
Adult-onset Still's disease (AOSD), a rare autoinflammatory disorder, resembles systemic juvenile idiopathic arthritis (SJIA). The superimposable clinical features of AOSD and SJIA suggest both phenotypes represent the same continuum with different ages onset. To further characterize similarity between at molecular level, 2 previously identified response gene sets in were used to investigate how genes that respond interleukin (IL)-1β inhibition canakinumab patients behave active prior IL-1β...
An important recent advance in the functional analysis of Saccharomyces cerevisiae genes is development one-step PCR-mediated technique for deletion and modification chromosomal genes. This method allows very rapid gene manipulations without requiring plasmid clones interest. We describe here a new set plasmids that serve as templates PCR synthesis fragments allow variety modifications. Using selectable marker S. TRP1 or modules containing heterologous Schizosaccharomyces pombe his5+...
HeLaHF cells are transformation revertants of cervical cancer HeLa and have lost anchorage-independent growth potential tumorigenicity. Activation tumor suppressor(s) was implicated previously in this reversion. In study, expression profiling analysis carried out to identify oncogenes that down-regulated cells. We found all three members the NR4A1/Nur77/NGFIB orphan nuclear hormone receptor subfamily (NR4A1, NR4A2, NR4A3) were revertant. Small interfering RNA-mediated down-regulation NR4A2...
The core oligosaccharide Glc3Man9GlcNAc2 is assembled at the membrane of endoplasmic reticulum on lipid carrier dolichyl pyrophosphate and transferred to selected asparagine residues nascent polypeptide chains. This transfer catalyzed by oligosaccharyl transferase complex. Based synthetic phenotype mutation wbp1 in combination with a deficiency assembly pathway Saccharomyces cerevisiae, we have identified novel ALG9 gene. We conclude that this locus encodes putative mannosyl because deletion...
Canakinumab is a human anti-interleukin-1β (IL-1β) monoclonal antibody neutralizing IL-1β-mediated pathways. We sought to characterize the molecular response canakinumab and evaluate potential markers of using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA).Gene expression was measured patients with febrile SJIA matched healthy controls by Affymetrix DNA microarrays. Transcriptional assessed gene changes baseline day 3 adapted JIA American College...
Cnm67p, a novel yeast protein, localizes to the microtubule organizing center, spindle pole body (SPB). Deletion of CNM67 (YNL225c) frequently results in misorientation and impaired nuclear migration, leading generation bi- multinucleated cells (40%). Electron microscopy indicated that is required for proper formation SPB outer plaque, structure nucleates cytoplasmic (astral) microtubules. Interestingly, microtubules are essential orientation migration still present cnm67Delta1 lack...
Saccharomyces cerevisiae cnm67Δ cells lack the spindle pole body (SPB) outer plaque, main attachment site for astral (cytoplasmic) microtubules, leading to frequent nuclear segregation failure. We monitored dynamics of green fluorescent protein–labeled nuclei and microtubules over several cell cycles. Early migration steps such as positioning orientation were slightly affected, but late phases rapid oscillations insertion anaphase nucleus into bud neck mostly absent. Analyzes microtubule...
Cancer arises by the accumulation of genetic alterations in DNA leading to aberrant gene transcription. Expression-profiling studies have correlated genomewide expression signatures with malignancy. However, functional analysis elucidating contribution and synergy genes specific cancer cell phenotypes remains a formidable obstacle. Herein, we describe an alternative approach for identification involved tumor progression using library zinc finger artificial transcription factors (ATFs)...
Abstract The efficiency of chemotherapeutic treatments in cancer patients is often impaired by the acquisition drug resistance. Cancer cells develop resistance through dysregulation one or more genes cellular pathways. To isolate efficient regulators tumor cells, we have adopted a genome-wide scanning approach based on screening large libraries artificial transcription factors (ATFs) made three and six randomly assembled zinc finger domains. Zinc were linked to VP64 activation domain...
Nuclear migration and positioning in Saccharomyces cerevisiae depend on long astral microtubules emanating from the spindle pole bodies (SPBs). Herein, we show by vivo fluorescence microscopy that cells lacking Spc72, SPB receptor of cytoplasmic γ-tubulin complex, can only generate very short (<1 μm) unstable microtubules. Consequently, nuclear to bud neck orientation anaphase along mother-bud axis are absent these cells. However,SPC72 deletion is not lethal because elongated but...
As part of EUROFAN (European Functional Analysis Network), we investigated 21 novel yeast open reading frames (ORFs) by growth and sporulation tests deletion mutants. Two genes (YNL026w YNL075w) are essential for mitotic three strains (ynl080c, ynl081c ynl225c) grew with reduced rates. (YNL223w YNL225c) were identified to be required sporulation. In addition also performed green fluorescent protein (GFP) tagging localization studies. GFP labelling indicated the spindle pole body...
<h3>Background</h3> Interleukin (IL)-1β plays a key role in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA). Canakinumab (CAN), selective, fully human, anti-IL-1β monoclonal antibody, has been shown to be efficacious treatment SJIA.<sup>1</sup> <h3>Objectives</h3> To analyze gene expression and inflammatory proteins blood SJIA patients (pts) on CAN therapy.To identify biomarkers that predict clinical response at baseline. <h3>Methods</h3> Inflammatory protein (IL-6; IL-18)...
This short communication focuses the on articular cartilage and subchondral bone, both of which play important roles in development osteoarthritis (OA). There are indications that estrogen-deficiency, as post-menopausal state, accelerate OA. We investigated, extracellular matrix (ECM) protein, proteases different pro-inflammatory factors was up- or down-regulated knee joint tissue response to estrogen-deficiency rats induced by ovariectomy. These data support previous findings several...
Adult-onset Still's disease (AOSD) is a rare auto-inflammatory disorder resembling similar pediatric syndrome known as systemic juvenile idiopathic arthritis (SJIA).[1] The superimposable and clinical features in SJIA AOSD suggest that both phenotypes represent continuum with (SJIA) more adult-onset (AOSD).[2] Analyses of gene expression profiles may be useful not only for classification, diagnosis, prognosis, but also to identify specific treatment effects counteract the underlying...