Fungi are increasingly causing life-threatening infections. Little is known about the mechanisms underlying these infections. We will compare the genomes of high and low virulent fungal strains to gain insides into the basis of these differences by using C. gattii as model of a globally highly pathogenic fungus. The findings will be generalized by comparing the obtained results with the genomes of other important pathogenic fungi to develop a scientific basis for better treatment strategies.
The fungal pathogen Cryptococcus neoformans is responsible for up to a million deaths annually, necessitating the development of novel antifungals. We have characterised the GTP biosynthesis enzyme IMP dehydrogenase, revealing it is critical for infection, and structural and functional analysis reveals routes to inhibitor specificity. In the proposed work will develop novel antifungal compounds that target this enzyme, as well as investigate related enzymes as potential future drug targets.
An Investigation Into Chromatin Dynamics In Host-pathogen Interactions And Fungal Virulence
Funder
National Health and Medical Research Council
Funding Amount
$700,585.00
Summary
Fungal infections represent a major health burden, with loss of lives that parallels malaria. Only a handful of antifungal therapeutics is available, and mortality remains very high (30% or more). By using molecular biology approaches and animal infection models, this project aims to characterize a new class of promising antifungal drug targets in the major human fungal pathogen Candida albicans. The outcomes will provide the knowledge foundation for future antifungal drug discovery.
Dissecting Virulence Attributes In A Human Pathogenic Fungus
Funder
National Health and Medical Research Council
Funding Amount
$814,596.00
Summary
Fungi that infect humans are a major health problem worldwide, particularly for those with compromised immune systems (eg. AIDS, transplant and cancer patients). These fungi cause disease by evading the immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells; a hostile and nutrient poor environment. This project will study genes that are required for growth inside host cells. This knowledge will open new avenues for treatment.
DNA Barcoding Of Pathogenic Fungi As The Basis For The Development Of Novel Standardized Diagnostic Tools
Funder
National Health and Medical Research Council
Funding Amount
$560,398.00
Summary
Fungal infections are increasing and have major health impacts, with a high economic burden. Timely initiation of therapy is the key to improve patient outcomes. However, reliable identification tools for fungal pathogens are lacking. We will use comparative genome analysis to develop unique fungal signatures (DNA barcodes) and establish an online database to allow for rapid identification for diagnosis in the clinical setting and as a quarantine tool for border protection.
T-follicular Helper Cell Subsets That Induce Protective Anti-Plasmodium Falciparum Antibodies
Funder
National Health and Medical Research Council
Funding Amount
$456,262.00
Summary
Malaria claims at least half a million lives each year, the majority of them in children under the age of 5 years. In order to development effective vaccines malaria it is critically important that we increase our understanding of the key mechanisms governing the induction of protective immune responses in naturally exposed populations. This project will examine the role of one important cell subset - T-follicular helper cells - in the development of immunity against malaria.
Identification Of Proteins Specific To Transmissible Pseudomonas Aeruginosa In Cystic Fibrosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$443,007.00
Summary
Cystic fibrosis (CF) is the most common autosomal recessive disorder in humans, affecting 1:2000 people. Mortality is often caused by Pseudomonas aeruginosa lung infections which have recently been shown to occur not only environmentally but also via person-person contact, usually during CF clinic visits. This project will elucidate the molecular traits responsible for these 'epidemic' P. aeruginosa infections, with the aim of finding novel therapeutics and infection control strategies.
Multistage Vaccines For The Prevention Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$884,290.00
Summary
Almost two million people die from tuberculosis (TB) each year. The current vaccine, BCG, is ineffective at controlling TB and the type of immune response needed to protect against the disease is poorly understood. We have discovered new antigens of the TB bacterium, and we will combine them with novel delivery strategies to develop new TB vaccines. We will also determine the type of immune response needed to protect against TB, which will aid progression of vaccines into clinical trials.
Delayed Loss Of Acoustic Hearing After Cochlear Implantation: Mechanisms And Clinical Identification With New Cochlear Implant Technology
Funder
National Health and Medical Research Council
Funding Amount
$1,040,157.00
Summary
Natural hearing can be combined with a cochlear implant to improve sound quality and speech understanding. However, natural hearing frequently deteriorates weeks to months after cochlear implantation. This seems to occur when cochlear fluid buildup (hydrops) or fibrosis within the inner ear disrupts cochlear mechanics. We plan to monitor these processes in patients by recording directly from the cochlear implant, and conduct laboratory experiments to find therapies to alleviate their effects.
Nanoengineered Drug Delivery To The Inner Ear To Prevent Progressive Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$479,056.00
Summary
Hearing loss is a common sensory deficit and can get progressively worse over time, eventually requiring a cochlear implant. In this project we will examine the effectiveness of a new technique that uses nanoengineered particles to provide long term and controlled delivery of drugs in order to prevent progressive hearing loss and protect residual hearing following cochlear implantation. We will develop the next generation of nanotechnology to enhance drug delivery in pathological ears.