A5061772377- Fungal and yeast genetics research
- Microbial Metabolic Engineering and Bioproduction
- Microbial Natural Products and Biosynthesis
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Antifungal resistance and susceptibility
- RNA and protein synthesis mechanisms
- Fungal Infections and Studies
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Fermentation and Sensory Analysis
- RNA Research and Splicing
- Carbohydrate Chemistry and Synthesis
- Mitochondrial Function and Pathology
- Pneumocystis jirovecii pneumonia detection and treatment
- Nail Diseases and Treatments
- Synthetic Organic Chemistry Methods
- CRISPR and Genetic Engineering
- Biotin and Related Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Plant-Microbe Interactions and Immunity
- Autophagy in Disease and Therapy
- Plant nutrient uptake and metabolism
RIKEN
2003-2024
RIKEN Center for Sustainable Resource Science
2017-2024
Pioneer (Japan)
2024
Target (United States)
2023
Genomics (United Kingdom)
2023
RIKEN Advanced Science Institute
2009-2013
Tohoku University
2010
Japan Biological Informatics Consortium
2010
National Institute of Advanced Industrial Science and Technology
2010
Japan Science and Technology Agency
2008
A novel series of plasmid vectors named pDUAL have been developed. These enable one to introduce not only multicopies genes with episomal maintenance but also a single copy chromosomal integration into the fission yeast, Schizosaccharomyces pombe. The multicopy plasmids can be easily converted fragments for by digestion certain restriction endonuclease before transformation yeast cells. resultant fragments, lacking autonomously replicating sequence, are designed targeting leu1 locus...
SDS-PAGE is a basic method that has long been used for separation of proteins according to their molecular sizes. Despite its simplicity, it provides information on characteristics beyond masses because gel mobility often reflects physicochemical properties and post-translational modifications. Here we report global analysis the proteome, which term "mobilitome," covering 93.4% fission yeast proteome. To our surprise, more than 40% did not migrate calculated positions. Statistical analyses...
Aberrant activation of Wnt/β‐catenin signaling causes tumorigenesis and promotes the proliferation colorectal cancer cells. Porcupine inhibitors, which block secretion Wnt ligands, may have only limited clinical impact for treatment cancer, because most is caused by loss‐of‐function mutations tumor suppressor adenomatous polyposis coli ( APC ) downstream ligands. Tankyrase poly( ADP ‐ribosyl)ates PAR ylates) Axin, a negative regulator β‐catenin. This post‐translational modification...
The canonical WNT pathway plays an important role in cancer pathogenesis. Inhibition of poly(ADP-ribose) polymerase catalytic activity the tankyrases (TNKS/TNKS2) has been reported to reduce Wnt/β-catenin signal by preventing poly ADP-ribosylation-dependent degradation AXIN, a negative regulator signaling. With goal investigating effects tankyrase and Wnt inhibition on tumor growth, we set out find small-molecule inhibitors TNKS/TNKS2 with suitable drug-like properties. Starting from 1a,...
Fungal pathogens pose a global threat to human health, with Candida albicans among the leading killers. Systematic analysis of essential genes provides powerful strategy discover potential antifungal targets. Here, we build machine learning model generate genome-wide gene essentiality predictions for C. and expand largest functional genomics resource in this pathogen (the GRACE collection) by 866 genes. Using chemogenomic analyses, define function three uncharacterized roles kinetochore...
Abstract Fungal infections cause more than 1.5 million deaths annually. With an increase in immune-deficient susceptible populations and the emergence of antifungal drug resistance, there is urgent need for novel strategies to combat these life-threatening infections. Here, we use a combinatorial screening approach identify imidazopyrazoindole, NPD827, that synergizes with fluconazole against azole-sensitive -resistant isolates Candida albicans . NPD827 interacts sterols, resulting profound...
Significance The Zika virus (ZIKV) causes various neurologic defects including microcephaly and the Guillain-Barré syndrome. However, little is known about how ZIKV those diseases or which viral protein(s) responsible for observed cytopathic effects involved in restricted neuronal cellular growth, dysregulation of cell cycle, induction hypertrophy death. A genome-wide analysis proteins peptides was conducted using fission yeast as a surrogate host. Seven conferred NS4A-induced growth...
Rising drug resistance among pathogenic fungi, paired with a limited antifungal arsenal, poses an increasing threat to human health. To identify compounds, we screened the RIKEN natural product depository against representative isolates of four major fungal pathogens. This screen identified NPD6433, triazenyl indole broad-spectrum activity all screening strains, as well filamentous mold Aspergillus fumigatus. Mechanistic studies indicated that NPD6433 targets enoyl reductase domain fatty...
Prions are protein-based infectious entities associated with fatal brain diseases in animals, but also modify a range of host-cell phenotypes the budding yeast, Saccharomyces cerevisiae. Many questions remain about evolution and biology prions. Although several functionally distinct prion-forming proteins exist S. cerevisiae, [HET-s] Podospora anserina is only other known fungal prion. Here we investigated prion-like, epigenetic transmission fission yeast Schizosaccharomyces pombe. We show...
Tankyrases (TNKS/TNKS2) belong to the poly(ADP-ribose) polymerase family. Inhibition of their enzymatic activities attenuates Wnt/β-catenin signaling, which plays an important role in cancer pathogenesis. We previously reported discovery RK-287107, a spiroindoline-based, highly selective, potent tankyrase inhibitor. Herein we describe optimization process RK-287107 leading RK-582, exhibits markedly improved robust tumor growth inhibition COLO-320DM mouse xenograft model when orally...
Non- Candida albicans species (NCAC) are on the rise as a cause of mycosis. Many antifungal drugs less effective against NCAC, limiting available therapeutic agents.
A common strategy for identifying molecules likely to possess a desired biological activity is search large databases of compounds high structural similarity query molecule that demonstrates this activity, under the assumption predictive similar activity. However, efforts systematically benchmark diverse array available molecular fingerprints and coefficients have been limited by lack large-scale datasets reflect similarities compounds. To elucidate relative performance these alternatives,...
ABSTRACT Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number drugs available to combat this disease. In manuscript, we show host defense peptide mimetic brilacidin (BRI) as promising antifungal drug against C. . BRI can affect organization cell membrane, increasing permeability. We also investigated effects model system Saccharomyces cerevisiae analyzing libraries...
Abstract Microbes have evolved intricate communication systems that enable individual cells of a population to send and receive signals in response changes their immediate environment. In the fission yeast Schizosaccharomyces pombe , oxylipin nitrogen signaling factor (NSF) is part such system, which functions regulate usage different sources. Yet, pathways mechanisms by NSF acts are poorly understood. Here, we show physically interacts with mitochondrial sulfide:quinone oxidoreductase Hmt2...
The total synthesis of destruxin E (1) has been achieved for the first time, and stereochemistry its chiral center at epoxide determined to be (S). cyclization precursor 3a was synthesized by solid-phase peptide synthesis. Macrolactonization utilizing MNBA-DMAPO, followed formation epoxide, then furnished E. Its diastereomer, epi-destruxin (2), also in same manner. Furthermore, biological evaluation indicated that exhibits V-ATPase inhibitory activity 10-fold greater than
Identification of the cellular target small molecules is a major challenge to developing biological tools and drug leads. Here we report novel microarray-based system for identification or pathway using set drug-hypersensitive fission yeast strains that collectively overexpress each gene in open reading frame-ome. The advantage this method it provides genome-wide interrogation but requires relatively amount test compound. Using system, identified 28 genes linked etoposide sensitivity, which...