Improving Synthetic Methodology To Prepare Pre-clinical Analogues Of Human Insulin
Funder
National Health and Medical Research Council
Funding Amount
$457,708.00
Summary
The glucose regulatory hormone, insulin, remains the only treatment for type I diabetes and up to 30% of type II diabetes, both of which are among the world’s fastest growing chronic diseases today. Because insulin, if taken orally, would be broken down quickly, it has usually been given by injection. This project will develop novel chemical methods for the efficient preparation of novel insulin therapeutics with improved stability and oral bioavailability for prolonged treatment of patients.
Dissecting Rapamycin Sensitive And Insensitive Effects Of MTOR
Funder
National Health and Medical Research Council
Funding Amount
$1,183,241.00
Summary
All cells possess machinery that can sense nutrient availability and trigger cell growth and nutrient storage pathways. However, nutrient oversupply is detrimental to health. Recently, it was shown that drugs that inhibit the nutrient sensors have life extending effects. Our laboratory has discovered a novel mechanism by which these drugs might be mediating these beneficial effects that could change the way we think about the beneficial effects of these drugs and their mode of action
Further Development Of The Clinical Potential Of H2 Relaxin
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
The hormone relaxin mediates cardiovascular and kidney changes during pregnancy. These important functions have led to its current use in clinical trials for the treatment of acute heart failure, a condition affecting millions of patients worldwide. However, there is an urgent need for a longer lasting form of relaxin for prolonged treatment of patients. Our studies will focus on understanding the blood breakdown of the peptide to lead to the design of longer lasting relaxin analogues.
The Novel Role Of Eukaryotic Elongation Factor 2 Kinase (eEF2K) In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$650,531.00
Summary
Atherosclerosis causes build up of cholesterol plaques inside blood vessels that cause heart attacks and strokes. Macrophages are a type of cell that accumulate inside these plaques to make them grow. We work with a molecule called eukaryotic elongation factor 2 kinase (eEF2K), that controls how cells in the body divide and survive. We are studying how eEF2K controls the macrophage build up in plaque to develop new treatments against atherosclerosis that can stop heart attacks and strokes.
Codon Bias: A Hidden Layer Of Translational Regulation By Estrogens
Funder
National Health and Medical Research Council
Funding Amount
$420,922.00
Summary
The hormone estrogen signals through its receptors to mediate both transcription in the nucleus and signalling known to affect translation in the cytoplasm. It is currently unknown in which way the response to estrogen is orchestrated by integrating the translation of messenger RNAs with the transcription of target genes. The project aims to determine how estrogen signalling is integrated by carefully dissecting how messenger RNAs are transcribed and translated under its control.
Development Of New Anticancer Drugs Using Sortase-mediated Ligation
Funder
National Health and Medical Research Council
Funding Amount
$618,274.00
Summary
There is a great need for new cancer treatments. We are developing cyclic peptides as the next generation of safe and effective cancer drugs. Cyclic peptides, unlike their linear counterparts, display high stability and oral bioavailability, as well as high solubility and negligible immune response. One of the hurdles is the cyclisation process and we aim to develop enzyme-mediated cyclisation as a convenient and cost effective method for cyclic peptide production.
Mammalian cells have developed a complex signalling network responsible for monitoring and responding to changes in the levels of growth factors and the availability of nutrients, energy and oxygen in their environment. Deregulation of this network often results in uncontrolled cell growth and diseases including cardiac hypertrophy and cancer. This proposal aims to understand how this network controls cell growth and identify potential targets for diseases driven by uncontrolled growth.
Exploring The Role Of MicroRNA And Target Processing Variability In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
microRNAs are gene regulators with critical roles in heart disease. How interactions between microRNAs and their messenger RNA targets change during disease is poorly understood. We hypothesise that these interactions are critically affected by altered processing of microRNAs and targets. We will thus characterise and validate such differences in healthy and diseased hearts. This will define gene regulatory changes underpinning heart disease and contribute to the search for better treatment.
Charting The Interface Between Cellular Metabolic States And Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$653,196.00
Summary
The research successes of Molecular Biology and Biochemistry have given us detailed pictures of the regulatory and metabolic states of cells and tissues, yet we know little about how these states affect each other. We hypothesise the existence of regulatory interactions between ribonucleic acids, enzymes and metabolites to connect gene expression and metabolism. We will employ novel RNA Biology methods to discover such regulatory interactions in medically important cellular contexts.
Characterising The Topology And Function Of The Human M5C RNA Methylome
Funder
National Health and Medical Research Council
Funding Amount
$602,537.00
Summary
The role of the modified base 5-methylcytosine (m5C) as an epigenetic mark in DNA is well appreciated and intensely studied. By comparison, the cellular functions of the same base modification in RNA molecules, which function as working copies of the DNA genome, are poorly understood. This project will apply next generation sequencing technology to chart the occurrence of m5C in eukaryotic cellular RNAs and endeavour to unravel its function(s) in human biology and cancer.