Goodness-of-fit Testing Of Log-link Models For Categorical Outcome Data
Funder
National Health and Medical Research Council
Funding Amount
$260,863.00
Summary
Information about the health consequences of exposure to causal factors is obtained from mathematical models of observed data. Incorrect inferences are possible if the model does not adequately represent the data. Relative risk models are recommended for observations over time on a cohort of subjects, but it is not known how best to assess the adequacy of such models. This project will assess the performance of summary measures of goodness-of-fit when applied to relative risk models.
Design And Analysis Of Interrupted Time Series Studies In Health Care Research: Resolution Of Methodological Issues
Funder
National Health and Medical Research Council
Funding Amount
$307,125.00
Summary
An interrupted time series (ITS) study involves a population observed on multiple occasions before and after the implementation of an intervention program. However, methods for statistical analysis and designing such studies have not been well developed and many statistical analyses of such studies are flawed. This proposal will investigate appropriate methods for design and analysis, and develop guidelines and software for its implementation by health researchers.
Structure-based Design Of Inhibitors Of Oxidative Protein Folding In Enterobacteriaceae.
Funder
National Health and Medical Research Council
Funding Amount
$523,540.00
Summary
Antibiotic resistance represents a major public health problem. For gram-negative bacteria in particular, the situation is increasingly bleak, with the accumulation of resistance to existing drugs and few if any new drugs in the pipeline. We are using structure-based drug design to develop novel strategies for the treatment of gram-negative bacterial infections.
Development Of A Generic Strategy For The Stabilisation Of Peptide-based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$443,196.00
Summary
There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides the ....There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides therapeutically promising peptides and proteins the ability to resist the body s natural degradation pathways so they are able to reach their biological target. To develop this strategy we will use the recently discovered peptide hepcidin as a model system. Hepcidin is the major iron-regulatory hormone in the human body and incorrect levels of this hormone result in either iron overload (haemochromatosis), when there is not enough hepcidin produced by the body, or anemia of inflammation when there is too much hepcidin. The development of hepcidin-based therapeutic agents to treat these conditions has the potential to have significant impact as it has been estimated that up to 1 in 300 Australians are affected by haemochromatosis during their lifetimes. Unfortunately, unmodified peptides, like hepcidin, are of limited therapeutic value due to their poor stability within the human body. This research proposal describes the development of stabilised hepcidin analogues with the potential of being useful drug leads for the treatment of haemochromatosis.Read moreRead less
Exploitation Of Bacterial Transcription Initiation As A Target For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Antibiotic resistant infections from 'superbugs' are a major health problem. We will exploit information we have gathered on the machinery that copies genetic information into a message to discover chemical compounds that can be used for the development of new antibiotics with a novel mechanism of action.
Methods For Evaluating The Therapeutic Impact Of Diagnostic Tests - Development Of Guidelines
Funder
National Health and Medical Research Council
Funding Amount
$132,325.00
Summary
New diagnostic tests are frequently adopted in clinical practice without any evidence that they improve patient outcomes. This project will produce the first guidelines about the role and optimal design of studies assessing the impact of a new test on therapeutic decisions for conclusions about its clinical value. This work will inform researchers and clinicians to improve evidence-based diagnostic practice and promote the more efficient use of limited health care resources.
Great advances have been made in pharmaceutical design and discovery over the last 50 years. While drugs have traditionally been discovered using random screening of natural product libraries and chemical databases, new technologies in protein chemistry, structural and molecular biology have been adopted in efforts to speed the drug design process and increase its hit rate. In addition, our rapidly increasing knowledge of the molecular causes of many diseases provides us with many opportunities ....Great advances have been made in pharmaceutical design and discovery over the last 50 years. While drugs have traditionally been discovered using random screening of natural product libraries and chemical databases, new technologies in protein chemistry, structural and molecular biology have been adopted in efforts to speed the drug design process and increase its hit rate. In addition, our rapidly increasing knowledge of the molecular causes of many diseases provides us with many opportunities to develop therapeutics directed towards known molecular targets. Nevertheless, despite these advances, problems such as drug resistance and toxic side effects that compromise drug efficacy make it clear that there is a need for new classes of drugs with different modes of action. Because of their favourable properties, small-molecule drugs comprise by far the largest class of currently available therapeutics. However, in many cases, a drug derived from a protein may be preferable. The development of protein-based drugs is a youthful and rapidly expanding area of biotechnology, but to date, most studies have focused on targeting pathological events that occur on the outside of cells. We propose to use a combination of methods from molecular and structural biology, together with recently developed high-throughput screening techniques, to develop a generic protein drug scaffold that can be used as a template to develop therapeutics against a wide range of inappropriate interactions that may occur between molecules within cells.Read moreRead less