A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a ....A remarkable feature of bacterial cells though is that they can share genes. In so doing bacteria have the ability to acquire completely new characteristics. One example of this spreading of genes is the rapid dissemination of antibiotic resistance in pathogenic bacteria and the creation of multi-resistant superbugs. This process contributes greatly to the problem of hospiatal acquired infeections and results in many patient deaths annually. The other aspect of this sharing of genes is that in a population some cells will lack genes that others have. Some of these shared genes apart from antibiotic resistance can be a concern and include traits that make some bacteria pathogenic. Thus, two cells of the same species may have very different abilities to cause disease based on what additional genes they carry. Genomics is becoming one of the great scientific revolutions of the 21st century. Over 160 microbial genomes have been sequenced to date and from these studies we have also learned many important things including how some bacteria cause disease. Mobile DNA presents unique challenges to microbial genomics however since different individuals in a species can have many different genes. Thus genomics on even many individuals of a species may miss bacterial genes important to us. Here we will be applying genomics in a way that specifically targets those genes that are shared. This will have many benefits. We will be able to greatly increase our rate of discovery of medically important and other genes in way that is targeted. This approach will allow us to discover these shared genes in a way that is much more cost effective and faster than conventional whole cell genomics. It will also allow us to gain an understanding of how benign bacteria associated with humans may act as reservoirs for passing on harmful genes to bacteria that cause hospital infections.Read moreRead less
Role Of Novel Mobile Elements In The Infiltration Of Antibiotic Resistance Genes Into Clinical Isolates.
Funder
National Health and Medical Research Council
Funding Amount
$421,650.00
Summary
Bacteria have a remarkable ability to capture and spread antibiotic resistance genes. This phenomenon is a particular problem in our hospitals and in the community as multi-drug resistant pathogenic organisms have been selected over time as a result of the use of antibitoics. Moreover the incidence of resistance appears to be on the increase. Once resistant strains appear they can greatly complicate the treatment of infections and the eradication of such pathogens from a hospital is both difficu ....Bacteria have a remarkable ability to capture and spread antibiotic resistance genes. This phenomenon is a particular problem in our hospitals and in the community as multi-drug resistant pathogenic organisms have been selected over time as a result of the use of antibitoics. Moreover the incidence of resistance appears to be on the increase. Once resistant strains appear they can greatly complicate the treatment of infections and the eradication of such pathogens from a hospital is both difficult and costly. We have been working on the problem of how antibiotic resistance genes are spread for a number of years and have identified a novel genetic element that can capture resistance genes by a process of site-specific recombination. This element, the integron, is common in mutli-drug resistant clinical isolates. To be captured by an integron, an antibiotic resistance gene has to be part of a mobile element known as a gene cassette. Although the application of antibiotics acts to amplify pathogens that are resistant and favours their persistance in hospitals, it is generally recognized that neither the gene cassette nor the drug resistance gene evolve in the hospital. Rather, these genes make their way into human pathogens from bacteria that normally reside in other environments, for example soil or water. In this project, we will investigate one route by which drug resistance genes and integrons might find their way into clinically relevant strains and what the sources of the resistance genes and gene cassettes might be. A greater understanding of these processes will help in developing strategies to limit the spread of drug resistant bacteria into and around hospitals.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
Epilepsy is a very common and serious brain disorder. Epilepsy often includes other disabilities, reduction in quality of life and is associated with increased risk of early death. 30% of people with epilepsy are unable to gain control of their seizures with currently available medications. The genetic causes of the large majority of epilepsy cases have not yet been found. This project aims to identify new genetic causes of epilepsy and its related disorders.
Treatment Of Genetic Liver Disease By Homologous Recombination In Vivo, Coupled With A Pharmoco-genetic Strategy For Selective Expansion Of Genetically Repaired Hepatocytes
Funder
National Health and Medical Research Council
Funding Amount
$920,836.00
Summary
This project seeks to exploit recent advancements in our ability to precisely “edit” and correct mutations underlying human genetic diseases. To improve therapeutic efficiencies of the system, we will deliver the technology using highly efficient virus-based systems and apply a novel post-repair selection process to preferentially repopulate the liver with gene-repaired cells. Demonstration of the strategy in a humanised mouse model will provide important preclinical data for human applications.
Understanding The Genetic Basis Of Breast Cancer: Translation To Primary And Secondary Prevention
Funder
National Health and Medical Research Council
Funding Amount
$2,731,372.00
Summary
We have identified >200 regions of the genome that contain variants that increase breast cancer risk. I will now focus on the main challenges i.e. to a) find the remaining genetic risk factors that will collectively explain all of the genetic risk, b) understand how these work, in particular which genes they influence and c) apply this knowledge to find and develop new drugs. Importantly, such drugs could be used not only to treat breast cancer, but also to prevent it in high-risk women.
Site-specific Integration Of Functional Genomic Loci: Applications In Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$442,664.00
Summary
Gene therapy strategies have traditionally focused on the delivery of therapeutic genes by viral vectors. Mindful of the limitations and potential problems of viral gene delivery, non-specific viral integration and limited transgene expression, this investigation will explore the delivery and site-specific integration of large genomic fragments into human stem cells. It is anticipated this approach will avoid some of the problems associated with poor gene expression and insertional oncogenesis.
I aim to decipher the role of heritable, genetic DNA variation in human neurological disease. I will use next generation genomics technologies together with sophisticated cellular models to address the important questions of the biology of epilepsy and intellectual disability in particular. I aim to develop a treatment for a specific type of epilepsy, which affects only girls from the age of 6 months. My ultimate goal is to improve the life of the patients and their relatives.
Genetic And Phenotype Studies Of Partial Epilepsy In Gypsies
Funder
National Health and Medical Research Council
Funding Amount
$646,136.00
Summary
Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies ....Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies have proved particularly difficult to understand and the numerous genetic studies conducted so far have failed to produce important and replicable results. It is becoming increasingly clear that enormous genetic heterogeneity, with many rare mutations occurring in different affected subjects, will be a major obstacle to understanding the molecular basis of complex epilepsies. In this context, genetically isolated populations, which stem from a small number of ancestors, can be particularly helpful and revealing, since their limited genetic diversity means that the number of genes involved in causing complex epilepsies may be smaller and shared between individuals and families. In this study, we will analyze affected families, as well as non-familial cases of epilepsy, from a genetically isolated population - the European Roma-Gypsies. We will determine the number of potential susceptibility genes involved in familial forms, the overlap and differences between families, as well as the contribution of the genes identified in families to the development of sporadic epilepsy.Read moreRead less