Effects Of The Atrial Natriuretic Factor Enhancer And The 5'HS4 Insulator On The Probability Of Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$534,628.00
Summary
Complex organisms contain many different types of cells, which can have completely different appearances and functions. All of these cells contain the same genes; the differences between them are achieved by the selective use of the genes. The means by which the selective use of genes is accomplished is a key to understanding how complex organisms develop, and how that development goes awry in cancer, heart disease, and other common disorders. A very large body of evidence indicates that gene re ....Complex organisms contain many different types of cells, which can have completely different appearances and functions. All of these cells contain the same genes; the differences between them are achieved by the selective use of the genes. The means by which the selective use of genes is accomplished is a key to understanding how complex organisms develop, and how that development goes awry in cancer, heart disease, and other common disorders. A very large body of evidence indicates that gene regulation is accomplished by the interaction of protein factors with segments of DNA flanking the gene. One hypothesis underlying our work is that the flanking DNA elements act primarily to increase the probability that a gene will be active rather than silent. We will ask if removing a known regulatory element from the gene for Atrial Natriuretic Factor (ANF) in mice reduces the likelihood of ANF being expressed by heart cells when the heart is stressed. This experiment will also shed new light on an extremely common disease state in humans (cardiac hypertrophy). In a second experiment, we will use a new experimental system we have developed to ask if a gene regulatory element is able to dial up the amount of expression from a gene, as well as to switch the gene on. Our previous work suggested this was not the case, but we wish to conduct a more rigorous test. Another hypothesis is that no DNA element is able to completely shield a transferred gene from the regulatory elements surrounding it. Accordingly, we will test a DNA element that has been proposed to insulate any gene from all influences of surrounding genes, and ask if it is able to create an autonomously expressing gene at any site within the genome. Because they deal with functions that are common to all genes, these experiments will provide information that should be applicable to a broad array of efforts to manipulate gene expression.Read moreRead less
Identifying Long-range Regulatory Elements Of The Breast Cancer Susceptibility Gene, BRCA1
Funder
National Health and Medical Research Council
Funding Amount
$612,842.00
Summary
BRCA1 is a breast cancer susceptibility gene implicated in both familial and sporadic breast cancers. The mechanisms controlling BRCA1 expression are poorly understood. We will identify DNA sequences critical for regulation of the BRCA1 gene. We hypothesise that these regions are mutational hot spots conferring an increased breast cancer risk. A better understanding of the pathways responsible for promoting BRCA1-associated breast cancer will provide important diagnostic and treatment targets.
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