A5038109768- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Advanced Biosensing Techniques and Applications
- Pharmacogenetics and Drug Metabolism
- 3D Printing in Biomedical Research
- Fungal and yeast genetics research
- Semiconductor Quantum Structures and Devices
- Cell Image Analysis Techniques
- Semiconductor materials and interfaces
- DNA Repair Mechanisms
- Advanced biosensing and bioanalysis techniques
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Capillary Electrophoresis Applications
- Autophagy in Disease and Therapy
- Gene expression and cancer classification
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- Biosimilars and Bioanalytical Methods
- Microtubule and mitosis dynamics
- HER2/EGFR in Cancer Research
- Laser Material Processing Techniques
- Histone Deacetylase Inhibitors Research
- Drug Transport and Resistance Mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
Newcastle University
1981-2024
University of Newcastle Australia
2022
TD Bank
2019-2020
StemCells (United States)
2019
BioTek (United States)
2009-2012
PerkinElmer (United States)
2001-2002
PerkinElmer Biosignal
2001
Concordia University
1998
Oak Ridge National Laboratory
1998
Lawrence Livermore National Laboratory
1998
Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and requirement mitochondrial quality control mitophagy for physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal initiated superoxide signaling. Mitophagy was found be mediated PINK1/Parkin-dependent pathway involving p62 as a selective receptor (SAR). Importantly, this...
Saccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of orthologs in eukaryotes emphasizes a conserved role regulating sister chromatid cohesion, but homologs have not hitherto been identified outside certain fungi. Some metazoan were initially as developmental gene regulators, such Drosophila Nipped-B, regulator cut and Ultrabithorax, delangin, protein mutant Cornelia de Lange syndrome. We show delangin Nipped-B bind...
Abstract Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this accomplished include AR amplification and expression of splice variants, demonstrating that remains key therapeutic target advanced disease. For the first time we show IKBKE drives signalling PC. Significant inhibition regulated gene was observed upon siRNA-mediated depletion or pharmacological due inhibited multiple cell line models...
Nutrient fluctuations in the cellular environment promote changes cell metabolism and growth to adapt proliferation accordingly. The target of rapamycin (TOR) signalling network plays a key role coordination with nutrient and, importantly, limitation reduces TOR complex 1 (TORC1) signalling. We have performed global quantitative fitness profiling collection Schizosaccharomyces pombe strains from which non-essential genes been deleted. identified that regulate when cells are grown...
A universal feature of DNA damage and replication stress in eukaryotes is the activation a checkpoint-kinase response. In S-phase, checkpoint inhibits initiation, yet function this global block to origin firing remains unknown. To establish physiological roles arm checkpoint, we analyzed separation mutants budding yeast Saccharomyces cerevisiae that allow upon stress, despite an otherwise normal Using genetic screens, show lack checkpoint-block results dependence on pathways required for...
Fluorescence polarization assays in 384-well microtiter plates have been demonstrated. The performance is suitable for high throughput drug screening applications with respect to speed of analysis, displaceable signal, precision, and sensitivity various reagents. Rank order potency was maintained relative [(125)I]-ligand filtration assays, the effects highly colored compounds, tartrazine Chicago Sky Blue, were insignificant on signal up a concentration 1 microM. These attributes suggest that...
Impairment of autophagy leads to an accumulation misfolded proteins and damaged organelles has been implicated in plethora human diseases. Loss actively respiring cells also shown trigger metabolic collapse mediated by the depletion nicotinamide adenine dinucleotide (NAD) pools, resulting cell death. Here we found that deficit autophagy-NAD axis underpins loss viability models a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux NPC1...
Fluorescence polarization must be classified as a unique detection method relative to other intensity-based methods because both bound and unbound tracer is measured. Other fluorescence techniques require either physical removal of or means for distinguishing only tracer. The presence in the volume has profound consequences on how assay performance gauged. intent here provide tools accurate assessment discuss some practical considerations necessary understanding advantages limitations...
One of the few direct means identifying position localised states within band gap semiconductors entails measurement radiative transitions between bound and host crystal bands. Studies temperature dependence spectra supply information from which phonon contribution can be extracted, but electronic to transition probability its physical signature remain poorly understood. Accordingly, authors have employed their Green function technique calculate components optical cross section for deep...
Cell-based drug absorption assays, such as Caco-2 and MDCK-MDR1, are an essential component of lead compound ADME/Tox testing. The permeability transport data they provide can determine whether a continues in the discovery process. Current methods typically incorporate 24-well microplates performed manually. Yet need to generate earlier process, on increasing number compounds, is driving use higher density plates. A simple, more efficient process that incorporates 96-well permeable supports...
G protein-coupled receptors (GPCRs) represent the single largest molecular target of therapeutic drugs currently on market, and are also most common in high throughput screening assays designed to identify potential new drug candidates. A large percentage these now formatted as radioligand binding assays. Fluorescence polarization ligand can offer a non-rad alternative In addition, fluorescence homogenous format that is easy automate for screening. We have developed series peptide ligands...
For pt.I see ibid., vol.17, p.2575 (1984). The authors present the results of their calculations on ideal and reconstructed vacancy divacancy in silicon Jahn-Teller distorted cation anion vacancies gallium phosphide zinc selenide. they find that charge density profile, defect potential parameters are all agreement with existing obtained from self-consistent Green function methods. They also a consistent description dangling bond. An analysis localised structure is given, argue...
The use of weakly ionized plasmas as spectroscopic sources for materials sampling and analysis is reviewed. Plasma currently used this purpose include direct-current alternating-current plasmas, inductively coupled microwave-induced surface-wave capacitively capacitive microwave glow discharges, flowing afterglows, theta pinch exploding films wires, laser-produced plasmas. authors give a summary relevant characteristics some the plasma sources. Included are source, common method application,...
Kinases continue to be one of the most important targets in today’s drug discovery efforts. Following identification lead compounds through screening efforts, it is profile these leads against other kinases within that family, as well from families, ascertain potential off-target effects. Because many kinase assays require use different substrates, optimization time and costs during profiling can prohibitive. Here we demonstrate versatility a luminescent ADP accumulation assay, where set...
The uridine 5'-diphospho-glucuronosyltransferase (UGT) family of enzymes is involved in the metabolism various compounds. These transfer a hydrophilic glucuronic acid moiety to their substrates, rendering them more water soluble and amenable excretion. UGTs act on endogenous such as bilirubin, 17β-estradiol, testosterone, drugs other xenobiotics. function these essential for clearance toxicants, alteration UGT activity potential cause adverse drug-drug interactions vivo. This has stimulated...
Direct reprogramming of human somatic cells toward induced pluripotent stem holds great promise for regenerative medicine and basic biology. We used a high-throughput small interfering RNA screening assay in the initiation phase 784 genes belonging to kinase phosphatase families identified 68 repressors 22 effectors. Six new candidates family G protein-coupled receptors (GPCRs) were identified, suggesting an important role this key signaling pathway during cell-induced reprogramming....
Cytochrome P450 (CYP) enzymes are key players in drug metabolism. Therefore, it is essential to understand how these can be affected by xenobiotics with regards induction and toxicity avoid potential drug-drug interactions. Typically, information has been gathered combining data from multiple experiments, which time-consuming labor intensive, interassay variability may lead misinterpretation. Monitoring CYP cytotoxicity using an automated, multiplexed format decrease workload increase...
Functional telomeres are critically important to eukaryotic genetic stability. Scores of proteins and pathways known affect telomere function. Here, we report a series related genome-wide interaction screens performed on budding yeast cells with acute or chronic defects. Genetic interactions were examined in defective Cdc13 Stn1, affecting two components CST, single stranded DNA (ssDNA) binding complex that binds telomeric DNA. For comparison, also defects Rfa3, the major ssDNA protein, RPA,...
Abstract In mammalian cell culture, the Golgi apparatus fragment upon DNA damage. GOLPH3, a component, is phosphorylation target of DNA-PK after damage and contributes to fragmentation. The function yeast (Saccharomyces cerevisiae) ortholog Vps74, in response has been little studied, although genome-wide screens suggested role at telomeres. this study we investigated Vps74 telomeres response. We show that decreases fitness telomere defective cdc13-1 cells yku70Δ cells. Importantly, loss...
Growth of most rod-shaped bacteria is accompanied by the insertion new peptidoglycan into cylindrical cell wall. This insertion, which helps maintain and determine shape cell, guided a protein machine called rod complex or elongasome. Although proteins in this are essential under normal growth conditions, viability can be rescued, for reasons that not understood, presence high (mM) Mg 2+ concentration. We screened natural product compounds could rescue mutants affected rod-complex function....