METABOLOMIC ANALYSIS OF MICROBIAL PATHOGENS
Grant number: 1059530 | Funding period: 2014 - 2018
Infectious diseases such as malaria, leishmaniasis and tuberculosis cause enormous morbidity and mortality worldwide. This proposal will utilize advanced analytical and genetic approaches to study the metabolism of the respective protozoan and bacteria agents as well as the associated host responses. These approaches will be used to develop novel therapeutic approaches and new analytical tools that can be applied to other infectious diseases
Related publications (11)
Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjaerg syndrome
Yilin Kang, Alexander J Anderson, Thomas Daniel Jackson, Catherine S Palmer, David P De Souza, Kenji M Fujihara, Tegan Stait, Ann E Frazier, Nicholas J Clemons, Deidreia Tull, David R Thorburn, Malcolm J McConville, Michael T Ryan, David A Stroud, Diana Stojanovski
Human Tim8a and Tim8b are members of an intermembrane space chaperone network, known as the small TIM family. Mutations in TIMM8A ..
Leishmania mexicana can utilize amino acids as major carbon sources in macrophages but not in animal models
Eleanor C Saunders, Thomas Naderer, Jenny Chambers, Scott M Landfear, Malcolm J McConville
Leishmania parasites target macrophages in their mammalian hosts and proliferate within the mature phagolysosome compartment of th..
Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex
Yilin Kang, David A Stroud, Michael J Baker, David P De Souza, Ann E Frazier, Michael Liem, Dedreia Tull, Suresh Mathivanan, Malcolm J McConville, David R Thorburn, Michael T Ryan, Diana Stojanovski
Acylglycerol kinase (AGK) is a mitochondrial lipid kinase that catalyzes the phosphorylation of monoacylglycerol and diacylglycero..
Analysis of Mammalian Cell Proliferation and Macromolecule Synthesis Using Deuterated Water and Gas Chromatography-Mass Spectrometry
Victoria C Foletta, Michelle Palmieri, Joachim Kloehn, Shaun Mason, Stephen F Previs, Malcolm J McConville, Oliver M Sieber, Clinton R Bruce, Greg M Kowalski
Deuterated water (²H₂O), a stable isotopic tracer, provides a convenient and reliable way to label multiple cellular biomass compo..
Metabolomics-Based Screening of the Malaria Box Reveals both Novel and Established Mechanisms of Action
Darren J Creek, Hwa H Chua, Simon A Cobbold, Brunda Nijagal, James I MacRae, Benjamin K Dickerman, Paul R Gilson, Stuart A Ralph, Malcolm J McConville
High-throughput phenotypic screening of chemical libraries has resulted in the identification of thousands of compounds with poten..
Reversing diet-induced metabolic dysregulation by diet switching leads to altered hepatic de novo lipogenesis and glycerolipid synthesis
Greg M Kowalski, Steven Hamley, Ahrathy Selathurai, Joachim Kloehn, David P De Souza, Sean O'Callaghan, Brunda Nijagal, Dedreia L Tull, Malcolm J McConville, Clinton R Bruce
In humans, low-energy diets rapidly reduce hepatic fat and improve/normalise glycemic control. Due to difficulties in obtaining hu..
Regulation of Starch Stores by a Ca2 -Dependent Protein Kinase Is Essential for Viable Cyst Development in Toxoplasma gondii
Alessandro D Uboldi, James M McCoy, Martin Blume, Motti Gerlic, David JP Ferguson, Laura F Dagley, Cherie T Beahan, David I Stapleton, Paul R Gooley, Antony Bacic, Seth L Masters, Andrew I Webb, Malcolm J McConville, Christopher J Tonkin
Transmissible stages of Toxoplasma gondii store energy in the form of the carbohydrate amylopectin. Here, we show that the Ca(2+)-..
In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic-hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach
Greg M Kowalski, David P De Souza, Steve Risis, Micah L Burch, Steven Hamley, Joachim Kloehn, Ahrathy Selathurai, Robert S Lee-Young, Dedreia Tull, Sean O'Callaghan, Malcolm J McConville, Clinton R Bruce
RATIONALE: Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the r..
Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse
Greg M Kowalski, David P De Souza, Micah L Burch, Steven Hamley, Joachim Kloehn, Ahrathy Selathurai, Dedreia Tull, Sean O'Callaghan, Malcolm J McConville, Clinton R Bruce
RATIONALE: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on..
Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites
Anubhav Srivastava, Darren J Creek, Krystal J Evans, David De Souza, Louis Schofield, Sylke Mueller, Michael P Barrett, Malcolm J McConville, Andrew P Waters
Human malaria parasites proliferate in different erythroid cell types during infection. Whilst Plasmodium vivax exhibits a strong ..
Characterization of Metabolically Quiescent Leishmania Parasites in Murine Lesions Using Heavy Water Labeling
Joachim Kloehn, Eleanor C Saunders, Sean O'Callaghan, Michael J Dagley, Malcolm J McConville
Information on the growth rate and metabolism of microbial pathogens that cause long-term chronic infections is limited, reflectin..