Primaquine Radical Cure Of Plasmodium Vivax Malaria: A Risk-benefit Analysis
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Vivax malaria causes significant morbidity with over 100 million clinical cases each year and can cause a relapsing illness and chronic anaemia. The only available radical cure of P. vivax requires administration of primaquine, which can cause severe haemolysis in some patients. Our research aims to determine the risks and benefits of giving primaquine to cure vivax malaria using data from meta-analyses of published clinical trials and individual patient results from large multicentre trials.
Functional Genomic Analysis Of The NKT Cell Control Locus Nkt1 And The Bana3/Babs2 Lupus Susceptibility Locus
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
The major populations of white blood cells responsible for learned immunity are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body's own tissues, resulting in autoimmune diseases such as lupus, in which antibodies are deposited in the tissues causing inflammation in organs such as the brain, skin and especially the kidneys. Another population of ....The major populations of white blood cells responsible for learned immunity are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body's own tissues, resulting in autoimmune diseases such as lupus, in which antibodies are deposited in the tissues causing inflammation in organs such as the brain, skin and especially the kidneys. Another population of white blood cells, termed NKT cells, plays an important role in keeping the T and B cells in check, and we have found that these cells are deficient in an inbred mouse strain, NOD mice, which develop lupus after exposure to a particular type of bacteria, called mycobacteria. We have found that one of the major genes conferring susceptibility to lupus in these mice lies in the same genetic region as the major gene controlling NKT cell numbers, raising the possibility that the deficiency in NKT cells in this strain predisposes it to developing lupus. The experiments proposed for this project are divided into two groups. The first group test whether increasing NKT cell numbers by either injecting them, or else transferring genes that allow more to develop naturally, can affect the risk of developing lupus. The second group of experiments examine the potential roles of two specific genes which are in the genetic region of interest, and which we think might control both NKT cell numbers and lupus susceptibility. The approach to be used involves sophisticated techniques of genetic analysis, such as the use of mutant mice which carry genetic mutations near the relevant genes, and congenic mice, which are like NOD mice, but carry in addition to NOD genes, genetic regions from a non-autoimmune strain.Read moreRead less
Red Cell Disorders And The Regulation Of Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Iron is an essential nutrient, but it is also toxic when present in excess, so the amount of iron moving into and around the body must be tightly controlled. In this project we will investigate how this body iron movement is regulated, and in particular the role played by macrophages, the cells that clean up old red blood cells. An understanding of this process will be of great benefit in the analysis and treatment of important blood diseases and disorders of iron metabolism.
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new treatments.
NMR Of Red Cells: Plasma Membrane Oxidoreductase, And Cation Transport
Funder
National Health and Medical Research Council
Funding Amount
$192,388.00
Summary
An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknow ....An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknown; neither is the immediate source of the reducing equivalents (electrons) known. Novel, non-invasive, 13C NMR methods have been developed, and others are planned in this project, to study the rate of reduction of Otest? compounds, including 13C-ferricyanide, and reactions of 13C-ascorbate. This will provide a quantitative understanding of the kinetics of the redox reactions in the intact cell. The transfer of negative charges (electrons) from the cell, in the longer term (minutes) inevitably must be matched by the movement of cations (positive charges). The main cation flux is mediated by Na+, K+-ATPase, but various cation exchange pathways are also involved in the total Oionic economy? of the cell. Of special interest will be the calcium-activated K+ (or Gardos) channel. This Oopens? inappropriately in malaria, sickle cell anaemia, and under blood bank storage conditions, and this is thought to be the basis of some of the pathological events in these conditions. The alkali-metal cation exchange pathway ( Na+-Li+) is more activate in the red cells of many patients with hypertension. So, multiple-quantum NMR methods will be used to monitor membrane transport and binding of cations to characterise the kinetics and regulation of the K+-channel, and the Na+-Li+ exchange reactions. The significance will lie in a basic understanding of, and possible 'diagnostic methods' for the biochemical processes that occur in red blood cells in health and disease.Read moreRead less
Identification And Characterisation Of Novel Virulence Genes In Attaching And Effacing Strains Of Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$281,320.00
Summary
Some varieties of Escherichia (E.) coli are harmless bacteria that live in the healthy intestinal tract, whereas others can cause diarrhoea. Those varieties of E. coli which cause diarrhoea include so-called enteropathogenic E. coli (EPEC), which is a leading cause of life- diarrhoea in infants and young children in less developed countries, and enterohaemorrhagic E. coli (EHEC) the cause of hamburger disease. These bacteria are able to cause disease because they possess specific genetic informa ....Some varieties of Escherichia (E.) coli are harmless bacteria that live in the healthy intestinal tract, whereas others can cause diarrhoea. Those varieties of E. coli which cause diarrhoea include so-called enteropathogenic E. coli (EPEC), which is a leading cause of life- diarrhoea in infants and young children in less developed countries, and enterohaemorrhagic E. coli (EHEC) the cause of hamburger disease. These bacteria are able to cause disease because they possess specific genetic information that is absent from harmless varieties of E. coli. Although many of these disease-associated genes have been identified, the specific role of many of them is not known. In addition, it seems likely that many more genes of this type remain to be discovered. The fact that EPEC is host specific means that the mechanisms by which these bacteria cause disease can only be investigated in humans. This is extremely limiting for the number and type of investigations that can be performed. However, there are rabbit-specific strains of EPEC which cause a disease in rabbits that is indistinguishable from that caused by EPEC in children. The aims of this study are to use the rabbit model of diarrhoea to learn more about the contribution of certain specific factors of EPEC to disease causation and to discover new factors of this type. This will be achieved by three complementary strategies: (1) investigating rabbit E. coli for virulence genes and determining if they are present in human strains; (2) examining the effect of inactivating these genes on the ability of E. coli to cause diarrhoea in rabbits; and (3) infecting rabbits with pools of mutant E. coli strains to identify factors that the bacteria require to survive in rabbits. The results of these studies will improve understanding of the mechanisms by which E. coli cause disease and may provide opportunities for the development of novel tools to diagnose, treat and prevent E. coli-associated diarrhoea.Read moreRead less
Erythropoiesis Stimulating Agents are used to correct the anaemia associated with kidney disease, and cost Australia around $100m in 2004. The optimal target haemoglobin remains the subject of intense debate despite several large trials in the area. This project will use pooled data from these trials to provide a definitive analysis of the overall harms and benefits associated with different targets for the first time and will guide the use of these expensive drugs to maximise patient benefit.
So Like Your Mum! Is The Health Of Mothers In Far North Queensland Reflected In The Nutrition And Growth Of Their Children In Early Life?
Funder
National Health and Medical Research Council
Funding Amount
$96,631.00
Summary
The health, nutrition and growth of a baby reflect the health and nutrition status of its mother. We will link routine health service information for Indigenous mothers with information on the growth, haemoglobin and health of their young children to identify key factors in a mother’s pregnancy and before, influencing the future health and development of their babies. This study will shape interventions to improve the health of mothers, and thus improve the health of their children through life.