A5025401622- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Protein purification and stability
- Growth Hormone and Insulin-like Growth Factors
- Immune Cell Function and Interaction
- Alzheimer's disease research and treatments
- Viral Infectious Diseases and Gene Expression in Insects
- HER2/EGFR in Cancer Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Microfluidic and Capillary Electrophoresis Applications
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Cancer, Hypoxia, and Metabolism
- Angiogenesis and VEGF in Cancer
- Immunotherapy and Immune Responses
- Chemical Synthesis and Analysis
- Medicinal Plant Pharmacodynamics Research
- Toxin Mechanisms and Immunotoxins
- Axon Guidance and Neuronal Signaling
- Immunodeficiency and Autoimmune Disorders
- Blood disorders and treatments
- Cell Adhesion Molecules Research
- PI3K/AKT/mTOR signaling in cancer
CSL (Australia)
2008-2023
CSL (United Kingdom)
2015
The University of Melbourne
2014
The University of Queensland
2008
Ludwig Cancer Research
1987-2002
The Royal Melbourne Hospital
1987-2002
Walter and Eliza Hall Institute of Medical Research
1988-2002
Ludwig Cancer Research
1994-1996
Suppressor of cytokine signaling-3 (SOCS-3) is one member a family intracellular inhibitors signaling pathways initiated by cytokines that use, among others, the common receptor subunit gp130. The SH2 domain SOCS-3 has been shown to be essential for this inhibitory activity, and we have used quantitative binding analysis synthetic phosphopeptides map potential sites interaction with different components gp130 pathway. only high-affinity ligand found corresponded region centered around...
Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30-50% increase mature body size. Here we show that the SOCS2-/- is dependent upon presence of endogenous hormone (GH) and treatment with exogenous GH induced mice lacking both SOCS2. This was reflected terms overall weight, bone lengths, weight internal organs tissues. A heightened response to also measured examining GH-responsive genes expressed liver after administration. To further understand link between...
Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30–50% increase mature body size. Here we show that the SOCS2–/– is dependent upon presence of endogenous hormone (GH) and treatment with exogenous GH induced mice lacking both SOCS2. This was reflected terms overall weight, bone lengths, weight internal organs tissues. A heightened response to also measured examining GH-responsive genes expressed liver after administration. To further understand link between...
Cyclotides are plant derived mini-proteins with compact folded structures and exceptional stability. Their stability derives from a head-to-tail cyclized backbone coupled cystine knot arrangement of three-conserved disulfide bonds. Taking advantage this stable framework we developed novel VEGF-A antagonists by grafting peptide epitope involved in antagonism onto the cyclotide framework. Antagonists kind have potential therapeutic applications diseases where angiogenesis is an important...
A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, development has been confounded because of HCV's high degree antigenic variability and the preferential induction type-specific immune responses with limited potency against heterologous viral strains genotypes. We showed previously deletion three variable regions from E2 receptor-binding domain (Δ123) increases ability human broadly neutralizing antibodies...
Suppressor of cytokine signaling-3 (SOCS-3) and the protein tyrosine phosphatase SHP-2 both regulate signaling by cytokines interleukin-6 family, this is dependent upon recruitment to 757 in shared receptor subunit gp130. To better explore overlap ligand binding specificities exhibited these two regulators, we have mapped phosphopeptide preferences SH2 domains from SOCS-3 SHP-2. Degenerate libraries were screened against recombinantly produced determine sequences optimal ligands. We found...
IL-11 and receptor (R)alpha are induced by Th2 cytokines. However, the role(s) of endogenous in antigen-induced inflammation has not been fully defined. We hypothesized that IL-11, signaling via IL-11Ralpha, plays an important role aeroallergen-induced mucus metaplasia. To test this hypothesis, we compared responses aeroallergen ovalbumin (OVA) wild-type (WT) IL-11Ralpha-null mutant mice. also generated defined effects antagonistic mutein on pulmonary responses. Increased levels IgE,...
The kinetics, binding equilibria and stoichiometry of the interaction between epidermal growth factor soluble extracellular domain receptor (sEGFR), produced in CHO cells using a bioreactor, have been studied by three methods: analytical ultracentrifugation, biosensor analysis surface plasmon resonance detection (BIAcore 2000) fluorescence anisotropy. These studies were performed with an sEGFR preparation purified absence detergent mild two step chromatographic procedure employing anion...
The high affinity interleukin-6 (IL-6) signaling complex consists of IL-6 and two membrane-associated receptor components: a low but specific the converter/signal transducing protein gp130. Monomeric (IL-6M) dimeric (IL-6D) forms Escherichia coli-derived human extracellular ("soluble") portions (sIL-6R) gp130 have been purified in order to investigate effect dimerization on binding complex. Although IL-6D has higher for immobilized sIL-6R, as determined by biosensor analysis employing...
Murine epidermal growth factor (EGF), a 53 amino acid protein, has been modified by enzymic digestion, site-specific chemical reactions, and recombinant DNA technology. After trypsin digestion the EGF derivatives EGF1-48 (called EGF-T) EGF1-45 EGF-T2) were separated from residual C-terminal pentapeptide reversed-phase high-performance liquid chromatography. EGF-T competes for binding to receptors with same efficiency as EGF. The EGF-T2 derivative had no detectable receptor activity even at...
The β common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of haematopoietic cells via a receptor complex incorporating cytokine-specific α shared common (βc, CD131) receptor. Evidence from animal models recent clinical trials demonstrate that these are critical mediators the pathogenesis inflammatory airway disease such as asthma. However, no therapeutic agents, other than steroids,...
Blocking the action of inhibitory molecules at sites central nervous system injury has been proposed as a strategy to promote axonal regeneration and functional recovery. We have previously shown that genetic deletion or competitive antagonism EphA4 receptor activity promotes recovery in mouse model lateral hemisection spinal cord injury. Here we assessed effect blocking activation using antagonist EphA4-Fc rat thoracic contusive Using ledged tapered balance beam open-field testing, observed...
Abstract Activation of Fc receptors and complement by immune complexes is a common important pathogenic trigger in many autoimmune diseases so blockade these innate pathways may be an attractive target for treatment complex-mediated pathomechanisms. High-dose IVIG used to treat inflammatory diseases, several studies demonstrate that the therapeutic effects can recapitulated with portion. Further, recent data indicate recombinant multimerized molecules exhibit potent anti-inflammatory...
Membrane adsorbers (MA) are emerging as alternative unit operations in high-value protein separation due to their many benefits, including short residence times, low pressure drop, ease of scale-up and cost-effectiveness. Historically, the MA literature has been directed new membrane materials use a polishing step binding capacity. More recently, emergence bind-elute modalities extended application at industrial scale, move from established resin chromatography is feasible. To fill this gap...
Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest intravenous immunoglobulin (IVIg) may be efficacious the influenza setting. We investigated potential of human IVIg to ameliorate ferrets exposed either pandemic H1N1/09 virus (pH1N1) or pathogenic avian (H5N1). administered at time exposure led significant reduction lung viral load following pH1N1 challenge. In...
SOCS3 is a negative regulator of cytokine signalling that inhibits Janus kinase-signal transduction and activator transcription (JAK-STAT) mediated signal tranduction by binding to phosphorylated tyrosine residues on intracellular subunits various receptors, as well possibly the JAK proteins. consists short N-terminal sequence followed kinase inhibitory region, an extended SH2 domain C-terminal suppressor (SOCS) box. related protein, cytokine-inducible SH2-containing are unique among SOCS...