Philip W. Kuchel

ORCID: 0000-0003-4100-7332
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About
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Research Areas
  • NMR spectroscopy and applications
  • Advanced NMR Techniques and Applications
  • Erythrocyte Function and Pathophysiology
  • Advanced MRI Techniques and Applications
  • Ion channel regulation and function
  • Hemoglobin structure and function
  • Electron Spin Resonance Studies
  • Advanced Neuroimaging Techniques and Applications
  • Neonatal Health and Biochemistry
  • Metabolomics and Mass Spectrometry Studies
  • Amino Acid Enzymes and Metabolism
  • Lipid Membrane Structure and Behavior
  • Blood properties and coagulation
  • Protein Structure and Dynamics
  • Pancreatic function and diabetes
  • Molecular spectroscopy and chirality
  • Cardiac electrophysiology and arrhythmias
  • Metabolism and Genetic Disorders
  • Spectroscopy and Quantum Chemical Studies
  • Neuroscience and Neuropharmacology Research
  • Venomous Animal Envenomation and Studies
  • Nanopore and Nanochannel Transport Studies
  • Ion Transport and Channel Regulation
  • Enzyme Structure and Function
  • Cancer, Hypoxia, and Metabolism

The University of Sydney
2014-2024

Technical University of Denmark
2019

Agency for Science, Technology and Research
2011-2014

Japan Science and Technology Agency
2014

Singapore Bioimaging Consortium
2011-2013

Australian Red Cross Lifeblood
2011

Macquarie University
2011

Queensland University of Technology
2008-2009

Kyoto University
2008

The University of Melbourne
2007

A new method for studying membrane transport is presented. High resolution n.m.r. used to measure the distribution of small molecules between intracellular and extracellular compartments. The uses spin-echo techniques relies on a difference in magnetic susceptibility media inside outside cells. It also provides simultaneous information metabolic status cell. illustrated by study alanine lactate human erythrocyte.

10.1042/bj1800037 article EN Biochemical Journal 1979-04-15

2-Deoxy-D-glucose (2DG) is a known surrogate molecule that useful for inferring glucose uptake and metabolism. Although 13 C-labeled 2DG can be detected by nuclear magnetic resonance (NMR), its low sensitivity detection prohibits imaging to performed. Using chemical exchange saturation transfer (CEST) as signal-amplification mechanism, the phosphorylated 2DG-6-phosphate (2DG6P) indirectly in 1 H (MRI). We showed CEST signal changed with concentration, was reduced suppressing cerebral...

10.1038/jcbfm.2013.79 article EN Journal of Cerebral Blood Flow & Metabolism 2013-05-15

When the platypus ( Ornithorhynchus anatinus ) was first discovered, it thought to be a taxidermist’s hoax, as has blend of mammalian and reptilian features. It is most remarkable mammal, not only because lays eggs but also venomous. Rather than delivering venom through bite, do snakes shrews, male platypuses have venomous spurs on each hind leg. The genome sequence provides unique opportunity unravel evolutionary history many these interesting While searching for sequences antimicrobial...

10.1101/gr.7149808 article EN cc-by-nc Genome Research 2008-05-07

Abstract “Diffusion‐diffraction” experiments on water, yielding “ q ‐space” plots, were conducted suspensions of oxygenated (diamagnetic) human erythrocytes. (i) These displayed diffusion‐diffraction water; (ii) the shape ‐space plots depended direction along which diffusion was measured, thus implying alignment cells in magnetic field NMR spectrometer; (iii) anisotropy altered a predictable way by converting hemoglobin to paramagnetic form; (iv) shapes inhibiting water transport; (v)...

10.1002/mrm.1910370502 article EN Magnetic Resonance in Medicine 1997-05-01

Over the last 25 years, several mathematical models of erythrocyte metabolism have been developed. Although these identified key features in regulation and control metabolism, many important aspects remain unexplained. In particular, none satisfactorily accounted for 2,3-bisphosphoglycerate (2,3-BPG) metabolism. 2,3-BPG is an modulator haemoglobin oxygen affinity, hence understanding concentration blood transport. A detailed, comprehensive, realistic model presented that can explain...

10.1042/bj3420581 article EN Biochemical Journal 1999-09-05

Drug block of the human <i>ether-à-go-go</i>-related gene K<sup>+</sup> channel (hERG) is most common cause acquired long QT syndrome, a disorder cardiac repolarization that may result in ventricular tachycardia and sudden death. We investigated open versus inactivated state dependence drug by using hERG mutants N588K N588E, which shift voltage inactivation compared with wild-type but mutated residue remote from drug-binding pocket pore. Four high-affinity drugs (cisapride, dofetilide,...

10.1124/mol.108.049056 article EN Molecular Pharmacology 2008-08-13

Ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder, is associated with severe hyperammonemia accompanied by a high risk of neurological damage and death in patients presenting neonatal-onset form. Contemporary therapies, including liver transplantation, remain inadequate considerable morbidity, justifying vigorous investigation alternate therapies. Clinical evidence suggests that as little 3% normal enzyme activity sufficient to ameliorate neonatal phenotype,...

10.1038/mt.2009.88 article EN cc-by-nc-nd Molecular Therapy 2009-04-21

The erythrocyte is exposed to reactive oxygen species in the circulation and also those produced by autoxidation of hemoglobin. Consequently, erythrocytes depend on protection antioxidant glutathione. Mathematical models based realistic kinetic data have provided valuable insights into regulation biochemical pathways within but none satisfactorily accounted for glutathione metabolism. In current model, rate equations were derived enzyme-catalyzed reactions, each equation nonlinear algebraic...

10.1074/jbc.m109.067017 article EN cc-by Journal of Biological Chemistry 2010-05-25

The cytoplasmic N–terminal domain of the human ether–a–go–go related gene (hERG) K+ channel is critical for slow deactivation kinetics channel. However, mechanism(s) by which regulates remains to be determined. Here we show that solution NMR structure 135 residues hERG contains a previously described Per–Arnt–Sim (PAS) (residues 26–135) as well an amphipathic α–helix 13–23) and initial unstructured segment 2–9). Deletion 2–25, only 2–9) or replacement with flexible linker all result in...

10.1371/journal.pone.0016191 article EN cc-by PLoS ONE 2011-01-13

We recently identified phospholipase activity as a potential virulence factor of Cryptococcus neoformans. have now defined the nature produced by clinical isolate C. neoformans var. neoformans, under native conditions, 1H and 31P nuclear magnetic resonance (NMR) spectroscopy thin-layer chromatography (TLC) radiolabelled substrates. Glycerophosphocholine was NMR sole phospholipid degradation product reaction between substrate phosphatidylcholine (PC) cryptococcal culture supernatants...

10.1128/iai.65.2.405-411.1997 article EN Infection and Immunity 1997-02-01

Reduction of mortality associated with bacterial meningitis and postsurgical cerebral ventriculitis is dependent on early diagnosis institution appropriate therapy. Metabonomics rapidly defines metabolic profiles biological fluids through the use high-throughput analytical techniques combined statistical pattern recognition tools.Proton nuclear magnetic resonance (1H NMR)-based metabonomics was applied to (1) lumbar cerebrospinal fluid samples collected prospectively from a cohort patients...

10.1086/497836 article EN Clinical Infectious Diseases 2005-11-04

This is the first in a series of three papers [see also Mulquiney and Kuchel (1999) Biochem. J. 342, 579-594; 595-602] that present detailed mathematical model erythrocyte metabolism which explains regulation control 2,3-bisphosphoglycerate (2,3-BPG) metabolism. 2,3-BPG modulator haemoglobin oxygen affinity hence plays an important role blood transport delivery. paper presents vivo kinetic characterization synthase/phosphatase (BPGS/P), enzyme catalyses both synthesis degradation 2,3-BPG....

10.1042/bj3420567 article EN Biochemical Journal 1999-09-05

Differences in magnetic susceptibility between various compartments heterogeneous samples can introduce unanticipated complications to NMR spectra. On the other hand, an understanding of these effects at level underlying physical principles has led development several experimental techniques that provide data on cellular function are unique spectroscopy. To illustrate some key features we present, among a more general overview, results obtained with red blood cells and recently described...

10.1002/cmr.a.10066 article EN Concepts in Magnetic Resonance Part A 2003-01-01

1. The Thy-1 membrane glycoproteins from rat thymus and brain bound deoxycholate to 24% of their own weight as measured by equilibrium dialysis. binding occurred co-operatively at the critical micelle concentration deoxycholate, suggesting that bind a micelle, not detergent monomer. 2. From sedimentation-equilibrium deoxycholate-binding data molecular weights glycoprotein monomers were calculated be 18700 17500 for respectively. polypeptide part is thus 12500. 3. In absence or formed large...

10.1042/bj1690411 article EN Biochemical Journal 1978-02-01
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