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
Structure, Formation And Evolution Of Multiple Antibiotic And Mercury Resistance Regions In Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$550,500.00
Summary
Antibiotic resistance and particularly resistance to several different antibiotics simultaneously is becoming alarmingly common in bacteria that cause infectious diseases in humans and animals. New antibiotics are proving slow to appear and the most obvious way to increase the effectiveness and the useful lifetime of existing antibiotics is though attempting to reduce the prevalence of resistant bacteria. This can only be done using good surveillance that allows the places where resistant bacter ....Antibiotic resistance and particularly resistance to several different antibiotics simultaneously is becoming alarmingly common in bacteria that cause infectious diseases in humans and animals. New antibiotics are proving slow to appear and the most obvious way to increase the effectiveness and the useful lifetime of existing antibiotics is though attempting to reduce the prevalence of resistant bacteria. This can only be done using good surveillance that allows the places where resistant bacteria and resistance genes are present in large numbers, e.g. in food-production animals, in hospitals, in the human gut or in the environment, to be identified. Very little data of this type is available internationally and even less for the Australian situation. Using recent knowledge of resistance genes and modern molecular techniques the work will identify which resistance genes and combinations of resistance genes confering resistance to antibbiotics used either in the clinic or administered to food-producing animals or both are found in Australian isolates. By examining multiply antibiotic resistant isolates from these two and other sources the flow of resistance genes and resistant bacteria between these two reservoirs will be tracked accurately. This will allow the sources relevant to difficult to treat or untreatable infections acquired in the hospital setting to be identified and appropriate action taken.Read moreRead less
Identifying The Physiological Conditions That Promote Lateral Gene Transfer And Evolution Of New Streptococcal Pathovars
Funder
National Health and Medical Research Council
Funding Amount
$415,907.00
Summary
In the last few decades, the diseases caused by the three human pathogens, groups A, B and G streptococcus have undergone a transformation. The exchange of DNA between these species is speculated to play a role in this changing disease association. In this proposal we will identify the specific physiological and growth conditions that promote DNA transfer. Such information may help in our understanding of how new pathogenic strains of streptococci arise.
Exploiting Sexual Differences In Germline Biology To Resolve The Causes Of Germline Mutation
Funder
National Health and Medical Research Council
Funding Amount
$315,914.00
Summary
Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating dis ....Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating diseases, and for devising effective preventative and diagnostic measures. To attain this understanding necessitates establishing the mechanistic origins of germline mutagenesis. Two basic approaches are employed to understand this process. The first assesses the incidence of mutation in pedigrees. This identifies the spectrum of risk mutations underlying the specific disease surveyed. Because other biological processes also influence these observations, the results from this approach do not reflect the underlying germline mutation spectra and are therefore not translatable between diseases. As mutations are rare events, it is prohibitive to obtain sufficient observations to resolve the underlying mechanisms. The second approach employs comparative genomic data, and uses differences in germline biology to estimate sex-biased effects. This comparative approach benefits from the accumulation of mutations over vast periods of time. The approach has not, however, been applied to diagnose the mechanistic origins of mutations. In this project, we will apply the enormous volume of comparative sequencing data to relate components of the mutagenic spectrum with sexual differences in germline biology. The project will differentiate between different types of mutations, and their association with specific processes will be established. The results will be a determination of the relative contributions of different mechanisms of mutation to germline mutagenesis.Read moreRead less