Molecular Typing And Epidemiology Of Bordetella Pertussis In Australia
Funder
National Health and Medical Research Council
Funding Amount
$552,662.00
Summary
Pertussis, commonly known as whooping cough, is an acute respiratory disease caused by Bordetella pertussis. Despite more than half a century of vaccination, pertussis has remained endemic in Australia, causing epidemic outbreaks every 3 to 4 years. Indeed the incidence has been increasing in recent years with over 11,000 cases notified in 2005.Pertussis is the commonest of all vaccine preventable diseases targeted by the Australian standard vaccination schedule. To control pertussis, appropriat ....Pertussis, commonly known as whooping cough, is an acute respiratory disease caused by Bordetella pertussis. Despite more than half a century of vaccination, pertussis has remained endemic in Australia, causing epidemic outbreaks every 3 to 4 years. Indeed the incidence has been increasing in recent years with over 11,000 cases notified in 2005.Pertussis is the commonest of all vaccine preventable diseases targeted by the Australian standard vaccination schedule. To control pertussis, appropriate epidemiological surveillance must be implemented to monitor the circulating B. pertussis strains and emergence of any new strains, in particular those that escape the protection by vaccines. This project will use a novel genomic comparison approach to find variation known as single nucleotide polymorphisms (SNP) present around the genome. We will use these SNPs to analyse a large collection of Australian and worldwide isolates to identify those SNPs most suitable for typing and determine the optimal number of SNPs needed for discrimination. A standardized, consistent and reliable typing method for strain identification will be established. We will further develop an integrated method for detecting known variation in the genes encoding the five acellular vaccine antigens. A combined method for strain identification and detection of antigenic variation will then be developed for culture-independent typing, enabling identification of the strain infecting an individual directly from a clinical sample without the need for culture. This study will establish molecular methods for surveillance of pertussis in Australia, essential for further improvement of acellular pertussis vaccines and public health control measures.Read moreRead less
The Influence Of Alpha Actinins On Human Performance
Funder
National Health and Medical Research Council
Funding Amount
$542,500.00
Summary
There is a wide variation in skeletal muscle function in the general population. At one end of the spectrum are elite athletes who excel in a specialised area of sprint, power or endurance performance, while at the other end of the spectrum are individuals with muscle weakness due to inherited muscle disease. Part of this variation in human muscle performance is due to the genetic makeup of the individual. For example, world class sprinters have muscles which are genetically predisposed to gener ....There is a wide variation in skeletal muscle function in the general population. At one end of the spectrum are elite athletes who excel in a specialised area of sprint, power or endurance performance, while at the other end of the spectrum are individuals with muscle weakness due to inherited muscle disease. Part of this variation in human muscle performance is due to the genetic makeup of the individual. For example, world class sprinters have muscles which are genetically predisposed to generate maximal force at high speed. Similarly, the severity of muscle disease in an affected individual is influenced, in part, by other genes that affect normal muscle performance. The genes responsible for normal variations in muscle function in humans are unknown. The alpha-actinins are structural components of skeletal muscle. The two forms of alpha-actinin in skeletal muscle interact with a number of proteins involved in human muscle disease and thus likely contribute to the severity of muscle weakness in affected patients. Alpha-actinin-3 is present only in fast (type 2) fibres - the muscle fibres responsible for perfomance at high speed. We have identified a genetic change that results in absence of this protein in 1 in 5 people in the general population, without causing disease. We now have evidence that this genetic change, and hence whether or not muscle contains alpha-actinin-3, influences muscle performance in elite athletes. We will now use a variety of approaches to study the alpha-actinins in normal and diseased skeletal muscle. We will study the effect of changes (mutations) in the alpha-actinins in the muscle cells grown in the laboratory and in animal models. This work will impact on our understanding of how normal skeletal muscle functions, and the factors that influence human diversity in the general population.Read moreRead less
Genetic Variation And Host-parasite Interactions Of Sarcoptes Scabiei
Funder
National Health and Medical Research Council
Funding Amount
$294,536.00
Summary
Scabies is a disease of skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. Although up to 45 different host species can be infested by this mite, this organism is currently classified as a single species existing as multiple strains or varieties. Previous studies have failed to identify any structural differences between host-associated populations, suggesting a single gene pool. Our recent molecular study of scabies in people and dogs, from Aboriginal communities in the Northern ....Scabies is a disease of skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. Although up to 45 different host species can be infested by this mite, this organism is currently classified as a single species existing as multiple strains or varieties. Previous studies have failed to identify any structural differences between host-associated populations, suggesting a single gene pool. Our recent molecular study of scabies in people and dogs, from Aboriginal communities in the Northern Territory and the North and South Americas, using DNA fingerprinting techniques, suggested mites cluster by host species with no evidence of cross-transmission. However although this data seems to suggest that these sub-species deserve species status, another molecular study suggests Sarcoptes is a single species, presumably a result of interbreeding. Understanding interbreeding between populations is important in the control of the disease and in controlling resistance to acaricides. We wish to further characterise the genetic separation of different 'strains' or populations of mites by studying the evolutionary gene flow between host-associated populations. We will use a mitochondrial DNA marker that will clarify fine scale transmission processes and more clearly delineate the biological species status of S. scabiei. Recent in vitro data and clinical evidence in a patient with severe crusted scabies indicated resistance to ivermectin, the treatment of choice for these patients. We will investigate the role and genetic mechanisms of ivermectin resistance. This is important for future control programs, as acaricide resistance can spread rapidly in parasite populations.Read moreRead less
The Influence Of Alpha Actinins On Human Performance In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,989.00
Summary
We have identified a common genetic variation that results in absence of the fast muscle fibre protein, a-actinin-3, in over 1 billion people worldwide. Loss of a-actinin-3 influences elite athletic performance and skeletal muscle function in the general population by altering efficiency of muscle metabolism. We will now study mice and humans to determine how a-actinin-3 deficiency influences normal muscle function with age, response to exercise and the severity of human muscle disease.
Origins And Relationships Of Shigella And Enteroinvasive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$377,310.00
Summary
Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoe ....Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoea in less developed countries and has also caused large outbreaks in developed countries. It is now clear that Shigella and E. coli are really one species. EIEC and Shigella strains are variants of E. coli with humans as the only host. However separation of the two in all records and most studies means that there is no integrated understanding of the forms. We aim to study the relationships of Shigella and EIEC and expect significant insights into the origins of Shigella-EIEC. This will facilitate diagnosis and understanding of the disease(s) and lead to a far better classification . EIEC-Shigella strains have arisen from other E. coli independently. This has happened seven times in the derivation of Shigella and we expect more such events with EIEC. An interesting phenomenon during this process is that strains tend to lose metabolic functions. In this study we will look at what, why and how functions are lost. O antigens are important in evading the host immune system. Shigella strains obtained many O antigens, the majority apparently from other species. This is quite likely the key to its success. We will look at how Shigella obtained new O antigens. This project will be significant in the understanding of Shigell-EIEC, a very significant human pathogen, and in general for understanding emergence of new pathogens.Read moreRead less
Populations of viruses in an host can be very diverse and just as the behaviour of a population of humans can be very different to the behaviour of individuals in them, populations of viruses behave differently to the behaviour of individuals in them. This diversity may provide a survival advantage to the virus and it also may regulate the severity of the symptoms in an infected host. This study will provide important new information that will drive vaccine strategies and public health policy.