Genomic Characterisation Of Novel Inflammatory Regulators In A Mouse Model Of Disseminated Candidiasis
Funder
National Health and Medical Research Council
Funding Amount
$581,427.00
Summary
Genome biology offers great promise for the study of immune function, but new approaches are needed to build insights between data and disease. This project looks at the gene products used by mice susceptible to yeast infection and asks if the information is used differently in resistant animals. Blood-borne fungal infections are increasing in hospitals; we want to discover new immune gene products and understand how they contribute, so we can better predict the outcome of an infection.
Modelling The Cost-effectiveness Of Therapeutic Strategies For Invasive Candidiasis Among The ICU Population
Funder
National Health and Medical Research Council
Funding Amount
$282,733.00
Summary
ICU patients are vulnerable to fungal infections during their stay in hospital. These infections are costly to treat and pose real dangers to the patient with up to 1270 lives lost each year. The best way to diagnose and treat these infections is currently not known. Making an early and accurate diagnosis is difficult but important if the infection is to be managed appropriately. This research will show which management strategies are optimal for patients and health services.
An Investigation Into Mitochondrial Dynamics In The Human Pathogen Candida Albicans
Funder
National Health and Medical Research Council
Funding Amount
$581,966.00
Summary
Our goal is to find new therapies to treat infections with Candida albicans, a major human pathogen that causes highly fatal hospital-associated disease. We have identified the mitochondrion, the cellular powerhouse, as a promising target for the development of new anti-candida drugs. We will use innovative imaging and molecular approaches, together with experimental animal infection models to understand how mitochondria could be inhibited to treat life-threatening infections with Candida.
Treatment Of Asymptomatic Candidiasis In Pregnant Women For The Prevention Of Preterm Birth: A Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,714,148.00
Summary
Prevention of early birth is a global priority. This study will establish if a simple process of screening and treating asymptomatic thrush in pregnancy prevents early birth. If positive the results of this study will change pregnancy management across the world to ensure a healthier start to life.
Certain bacterial DNA repeats are prone to hyper mutation. Genes with these repeats, Contingency genes, are randomly switched on and off. This process, phase variation , generates diversity in a population. Recently we described a new class of contingency gene that methylates DNA. On-off switching of this gene leads to random switching of multiple genes; the phasevarion . We will define the impact of this system in bacteria causing meningitis and STDs.
Treatment Of Asymptomatic Candidiasis In Pregnant Women For The Prevention Of Preterm Birth: A Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,120,373.00
Summary
Being born too early is a leading cause of perinatal death and morbidity. This trial seeks to determine whether screening for and treating candidiasis in pregnancy reduces the risk of this serious health problem. The trial will discover whether a simple treatment in pregnancy can reduce preterm birth. If positive, the results will be relevant to the management of every pregnancy.
Elucidation Of Proteins Expressed By Pathogenic Fungi During Animal Infection
Funder
National Health and Medical Research Council
Funding Amount
$558,267.00
Summary
Fungi cause a diverse range of diseases and are very difficult to treat. This project looks at the proteins that are made by infectious fungi while they are causing disease in animal cells. Proteins made in particularly high abundance may be essential for the fungus to live and grow in animal tissues. By specifically targeting their production, it should be possible to stop the infection without harming the host cell.
Host Resistance And Protection Against Oral Candidasis
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Candida albicans is an important opportunistic pathogen, that is widely represented in general medical and dental practice, as well as in the hospital environment. Clinical observations indicate that defects in innate immunity predispose patients to disseminated infection, whereas a weakened cell-mediated immune response is commonly associated with chronic oral infections. Animal models of both chronic and acute oral candidiasis have been developed and characterised by the applicants, and these ....Candida albicans is an important opportunistic pathogen, that is widely represented in general medical and dental practice, as well as in the hospital environment. Clinical observations indicate that defects in innate immunity predispose patients to disseminated infection, whereas a weakened cell-mediated immune response is commonly associated with chronic oral infections. Animal models of both chronic and acute oral candidiasis have been developed and characterised by the applicants, and these have clearly implicated T cells in the process of recovery from primary infection. The models will now be used to analyse the effector mechanisms that lead to clearance of the yeast from the oral cavity, with a particular focus on the role of phagocytic cells, and their interaction with T cells. The acute model will be used to identify immunological variables that can act as markers of protection, and the effectiveness of therapeutic manipulations will be evaluated in the chronic model, with the ultimate aim of developing a protective vaccine for human infections.Read moreRead less
Synthetic Analogues Of The Actinomycin, Quinamycin And Nogalamycin Groups Of Antitumour Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$376,433.00
Summary
The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar ....The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar scenario in the treatment of adults with leakaemias and non-Hodgkins lymphomas. The underlying cause of drug resistance is the genetic instability of cancer cells which results in tumours that are heterogeneous, making it almost inevitable that a cancer cell will arise that is resistant to treatment. There are many mechanisms of resistance, some of which are peculiar to particular drug types, some are permeability barriers and some involve genetic deregulation of the biochemistry of cell death. One way of subverting resistance is by the use of drugs whose mechanism of action is novel so that the tumour is challenged to devise a new defense. Here, we are attempting to develop synthetic analogues of a class of naturally- occurring antitumour antibiotic whose mechanism of action is unusual but which has not been exploited by medicinal chemists because of the difficulty of the chemistry involved. These antibiotics work by binding to DNA and inhibiting the first step in the process whereby genes are turned into proteins. We have designed compounds that are chemically accessible that our preliminary work suggests mimic the DNA-binding and biological properties of the natural antibiotics. The proposed work will enable us to evaluate whether this new class of agent has experimental antitumour activity, particularly amongst drug-resistant tumours.Read moreRead less