A5017667786- Cancer-related Molecular Pathways
- Protease and Inhibitor Mechanisms
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Nicotinic Acetylcholine Receptors Study
- Genetic Neurodegenerative Diseases
- Protein Structure and Dynamics
- Mitochondrial Function and Pathology
- Growth Hormone and Insulin-like Growth Factors
- Epigenetics and DNA Methylation
- Advanced Proteomics Techniques and Applications
- Microtubule and mitosis dynamics
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Fetal and Pediatric Neurological Disorders
- Signaling Pathways in Disease
- Ion channel regulation and function
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Connective tissue disorders research
- Lipid metabolism and disorders
- Mentoring and Academic Development
- Collagen: Extraction and Characterization
Monash University
2011-2023
Murdoch Children's Research Institute
2015
Institute of Medicinal Plant Development
2014
Australian Regenerative Medicine Institute
2013
Walter and Eliza Hall Institute of Medical Research
2009-2012
St. Jude Children's Research Hospital
2003-2009
University of Tennessee at Knoxville
2006-2008
UConn Health
2006
University of Tennessee Health Science Center
2004
Commonwealth Scientific and Industrial Research Organisation
2000
Friedreich ataxia (FRDA) is an inherited neurodegenerative disease characterized by and cardiomyopathy. Homozygous GAA trinucleotide repeat expansions in the first intron of FXN occur 96% affected individuals reduce frataxin expression. Remaining are compound heterozygous for a expansion point/insertion/deletion mutation. We examined disease-causing mutations impact on structure/function clinical outcome FRDA.We compared information from 111 heterozygotes 131 with homozygous expansions....
Kv1.3 potassium channels maintain the membrane potential of effector memory (T<sub>EM</sub>) T cells that are important mediators multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. The polypeptide ShK-170 (ShK-L5), containing an N-terminal phosphotyrosine extension <i>Stichodactyla helianthus</i> ShK toxin, is a potent selective blocker these channels. However, stability study showed minor pH-related hydrolysis oxidation byproducts were exacerbated by increasing...
Villin, an epithelial cell actin-binding protein, severs actin in vitro and vivo. Previous studies report that phosphatidylinositol 4,5-bisphosphate (PIP(2)) regulates severing by villin, presumably interaction with villin. However, direct association of villin PIP(2) has never been characterized. In this report, we presented mutational analysis to identify the PIP(2)-binding sites Villin (human) binds a K(d) 39.5 microm, stoichiometry 3.3, Hill coefficient 1. We generated deletion mutants...
Yeast are capable of modifying their metabolism in response to environmental changes. We investigated the activity oxygen-dependent high-affinity iron uptake system Saccharomyces cerevisiae under conditions heme depletion. found that absence heme, due a deletion gene encodes δ-aminolevulinic acid synthase (HEM1), resulted decreased transcription genes belonging both and copper regulons, but not zinc regulon. Decreased regulon was expression sensitive transcriptional activator Aft1p....
Intrinsically disordered proteins are predicted to be highly abundant and play broad biological roles in eukaryotic cells. In particular, by virtue of their structural malleability propensity interact with multiple binding partners, thought specialized for signaling regulation. However, these concepts based on silico analyses translated whole genome sequences, not large-scale expressed living Therefore, whether broadly apply is currently unknown. Previous studies have shown that...
Intrinsically unstructured proteins (IUPs) represent an important class of primarily involved in cellular signaling and regulation. The aim this study was to develop methodology for the enrichment identification IUPs. We show that heat treatment NIH3T3 mouse fibroblast cell extracts at 98 °C selects majority these IUPs were cytosolic or nuclear These studies first large-scale experimental investigation intrinsically mammalian proteome. Keywords: • disordered proteomics proteome denaturation
Cone snail venoms are a rich source of peptides, many which potent and selective modulators ion channels receptors. Here we report the isolation characterization two novel conotoxins from venom Conus imperialis. These toxins contain cysteine framework, C-C-C-CC-C, has not been found in other described to date. We name it framework XXIII designate im23a im23b; cDNAs these exhibit signal peptide sequence, defines new K-superfamily. The disulfide connectivity mapped by chemical mapping...
The protein SPSB2 mediates proteosomal degradation of inducible nitric oxide synthase (iNOS). Inhibitors SPSB2-iNOS interaction may prolong the lifetime iNOS and thereby enhance killing persistent pathogens. We have designed a cyclic peptide, Ac-c[CVDINNNC]-NH2, containing key sequence motif mediating interaction, which binds to binding site on with Kd 4.4 nM, as shown by SPR, [(1)H,(15)N]-HSQC, (19)F NMR. An in vitro assay macrophage cell lysates showed complete inhibition interactions...
Interleukin-1 receptor-associated kinase 3 (IRAK3) modulates the magnitude of cellular responses to ligands perceived by interleukin-1 receptors (IL-1Rs) and Toll-like (TLRs), leading decreases in pro-inflammatory cytokines suppressed inflammation. The molecular mechanism IRAK3’s action remains unknown. IRAK3 functions as a guanylate cyclase, its cGMP product suppresses lipopolysaccharide (LPS)-induced nuclear factor kappa-light-chain-enhancer activated B cell (NFκB) activity. To understand...
We describe in molecular detail how disruption of an intermonomer salt bridge (Arg337-Asp352) leads to partial destabilization the p53 tetramerization domain and a dramatically increased propensity form amyloid fibrils. At pH 4.0 37 degrees C, mutant (p53tet-R337H), associated with adrenocortical carcinoma children, readily formed fibrils, while wild-type (p53tet-wt) did not. characterized these proteins by equilibrium denaturation, 13C(alpha) secondary chemical shifts, (1H)-15N...
Abstract The substrate specificity of porcine pepsin has been altered by site‐directed mutagenesis in an attempt to selectively cleave bovine hide collagen at only a few sites, similar cathepsin D, for the production high quality gelatin. Kinetic parameters were determined using chromogenic peptide substrates based on sequence Lys‐Pro‐Xaa‐Yaa‐Phe*Nph‐Arg‐Leu (where Xaa is Ile or Pro, Yaa Glu, Leu, Gln Lys, Nph p ‐nitrophenylalanine, and * site cleavage). Substitution Thr222 Glu287 within S 2...