Investigating The Aetiopathogenic Role Of Autoantibodies Against The M1 Muscarinic Acetylcholine Receptor In Patients With First Episode Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$830,986.00
Summary
Previously we have found that a proportion of patients with schizophrenia have elevated levels of antibodies that target one of the neurotransmitter receptors, the M1 muscarinic acetylcholine receptor, and that those patients who have the highest levels of antibodies tend to have more severe manifestations of some of the symptoms of schizophrenia. In this project, we will try to confirm this relationship, and also investigate further how this antibodies might be able to worsen specific symptoms.
Tissue Specific T Cells Mediate Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$1,253,980.00
Summary
T cells are immune cells that create dangerous and fatal drug allergies affecting the skin. An individual’s genetic makeup only partially explains predisposition to these reactions, we believe the missing link is contained in immune signatures specific to the skin. We aim to identify drug-specific T cells in the skin and develop a sensitive test to screen for rare, dangerous T cells in the blood. This will enable prediction and prevention of severe drug allergy and development of safer drugs.
Adaptation Of Hepatitis C To Host HLA-Restricted Immune Responses In Australian Populations
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Over 200,000 Australians are infected with the Hepatitis C Virus (HCV) and about 11,000 new infections are diagnosed each year. Around 25% of people infected with HCV will clear the virus while for individuals with chronic infection 10 to 20% will develop cirrhosis of the liver within the next 20-40 years. Differences in host genetic factors and viral variants will, in large part, explain the observed heterogeneity in the clinical outcome and course of HCV infection. The basic theory underpinnin ....Over 200,000 Australians are infected with the Hepatitis C Virus (HCV) and about 11,000 new infections are diagnosed each year. Around 25% of people infected with HCV will clear the virus while for individuals with chronic infection 10 to 20% will develop cirrhosis of the liver within the next 20-40 years. Differences in host genetic factors and viral variants will, in large part, explain the observed heterogeneity in the clinical outcome and course of HCV infection. The basic theory underpinning this research is that the evolution of viruses such as HCV and HIV are influenced by the HLA type of the individual (hots), in combination with the ability of the virus to mutate (rid itself of deleterious mutations) to avoid the host's immune challenge (analogous to drug resistance) even at the lesser cost of impairing viral fitness or replication. We have shown that this is dependent on the immune environment that the virus encounters in relation to which HLA alleles are present in the host, therefore the escape is context specific. After transmission to a new host who lacks the same HLA type, the virus eliminates the previously advantageous mutations which could potentially impair viral fitness. The current study will carry out HCV sequencing and HLA typing on approximately 500 people with HCV from multiple Centres in Australia in order to characterise the interaction between the viral and host genetic factors. A customised software programme, Epipop, has been designed to perform sophisticated statistical analyses on the generated data, and has been successfully applied to HIV vaccine design. The results of this study could help explain why some infected individuals can spontaneously clear their infection while others go on to severe liver disease and allow clinicians to anticipate the course of infection in individuals and plan their management accordingly. Furthermore, the results may facilitate the search for optimal therapeutic and vaccination strategies.Read moreRead less
Molecular Typing Of Salmonella Enterica Serovar Typhimurium
Funder
National Health and Medical Research Council
Funding Amount
$272,545.00
Summary
Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subd ....Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subdivide Typhimurium is phage typing, which is done only in major laboratories (2 in Australia). Phage typing is based on lysis patterns of a test isolate to a set of 34 phages. Phage typing has played a crucial role in tracking the organism, for example the emergence of a multidrug resistance new type (DT204c) in UK and US. The technique is simple but the problem is that reactions vary with slight change in conditions and scoring the reaction results is very subjective. We propose to replace the typing system with one based on the DNA method PCR, so it will be simple, fast and accurate. We will use a DNA fingerprinting technique called AFLP (amplified fragment length polymorphism) to find markers (DNA segments) that are specific to phage types and design PCR assays based on the markers we find. Such a typing system will retain the essence of phage typing by providing continuity of the valuable epidemiological database on phage types. Further the typing system could easily be expanded to accommodate any new types by finding more markers while the current phage typing system is very difficult to expand (last done in 1977 and is behind in our needs). This project will establish a general approach for designing typing systems based on molecular biology for other pathogens and could have a major impact on the surveillance of bacterial infections in the 21st century.Read moreRead less
Optimising Temporal Genomic Surveillance Of Salmonella Infections In Australia
Funder
National Health and Medical Research Council
Funding Amount
$763,447.00
Summary
Salmonella is a leading cause of the food-borne disease – salmonellosis. It is responsible for considerable morbidity and has an enormous economic cost. Molecular typing is the key to rapidly identify and control outbreaks. This project will optimise the use of whole genome sequencing for outbreak investigation and long term epidemiology. A surveillance system that integrates genome sequence and epidemiological data will be highly significant for outbreak investigation and disease prevention.