Development Of Oral Natruiretic Peptides For Congestive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$511,037.00
Summary
Congestive heart failure is fatal disease and a major disease burden for the community affecting nearly half a million Australians. Current therapies are inadequate. We seek to develop a new peptide therapy based on snake venom version of the human B type natriuretic peptide which has to be given by injection. We will produce an orally active, stable and effective treatment using a program of discovery involving testing in animals and cells.
Hormone Transport By Alpha-2-Macroglobulin: Novel Roles In Regulating Hormone Activity
Funder
National Health and Medical Research Council
Funding Amount
$602,857.00
Summary
Alpha-2-macroglobulin is a large protein in the blood known to bind and transport numerous hormones in the circulation. Our previous studies published in BLOOD (2009) and JBC (2013) have discovered an important role for this molecule in the transport and regulation of a peptide hormone. The studies proposed in this application have important implications for understanding new roles of alpha-2-macroglobulin in hormone binding and regulating the activity of hormones in disease states.
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