In 2011 there were over 360 million people with type 1 and type 2 diabetes worldwide, who will require insulin treatment. There is an urgent need for insulin analogues that provide effective control of blood glucose to avoid unwanted hypoglycemic or hyperglycemic events. We have developed two novel insulin analogues with unique properties and aim to understand their mechanism of action. This knowledge will present new opportunities for improved insulin mimetics for diabetes treatment.
Conformational Change In Insulin And Type I Insulin-like Growth Factor Receptor Upon Ligand Binding
Funder
National Health and Medical Research Council
Funding Amount
$415,365.00
Summary
Insulin and insulin-like growth factors bind to receptor molecules on the surfaces of cells. The binding event results in a signal being sent into the cell to initiate in the case of insulin, uptake of glucose into the cell and, in the case of the growth factors, normal human growth. Breakdown of these processes is implicated in a number of disease states, including diabetes, cancer and Alzheimer's disease. This Project aims to decipher the receptor triggering mechanism that is responsible for g ....Insulin and insulin-like growth factors bind to receptor molecules on the surfaces of cells. The binding event results in a signal being sent into the cell to initiate in the case of insulin, uptake of glucose into the cell and, in the case of the growth factors, normal human growth. Breakdown of these processes is implicated in a number of disease states, including diabetes, cancer and Alzheimer's disease. This Project aims to decipher the receptor triggering mechanism that is responsible for getting the signal into the cell.Read moreRead less
Epigenetic Regulation Of Self Renewal And Lineage Commitment In Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$1,104,930.00
Summary
The process by which all our mature blood cells are produced and sustained remains largely unknown. Underpinning the cell fate decisions made through blood cell development is the tightly regulated expression of key genes and proteins that subsequently direct the process of blood cell differentiation. This project will aim study and uncover the molecular mechanisms that coordinate the key gene expression programs that lead to normal blood cell development.
We are seeking to understand how the protein ADAR1 functions. When it is mutated, ADAR1 can cause a range of diseases, most notably in a subset of Aicardi-Goutieres syndrome (AGS) patients, an autoimmune disorder affecting the brain, immune system, and skin. We have identified how we think that changes in ADAR1 activity may ultimately cause disease. This application will allow us to test this mechanism experimentally.
A New Function For Histone Variants In The Tissue-specific Regulation Of Pre-mRNA Splicing
Funder
National Health and Medical Research Council
Funding Amount
$657,224.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.
Identification And Characterization Of A Novel Long Intergenic Noncoding RNA For The Therapy Of Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Survivors suffer from lifelong disabilities due to chemotherapy. In this application, we will define the role of gene amplification of a long intergenic non-protein-coding RNA in determining the biological effects of a neuroblastoma oncogene, and promoting neuroblastoma initiation and progression. We will also define the anti-cancer efficacy of therapies targeting the long intergenic non-protein-coding RNA.
Long non-coding RNAs (lncRNAs) were considered to be junk, until recently. They cannot make protein so they were thought to be impotent. Despite this dogma, we studied the function of one lncRNA, in detail. Our data suggests it is a master regulator of mesoderm formation, the precursor of all internal organs. In this grant we will determine how this regulator works in normal development and how we might use this knowledge to design new therapies.
Role Of RNA-binding Proteins In Cardiomyocyte Physiology
Funder
National Health and Medical Research Council
Funding Amount
$880,494.00
Summary
Interactions between ribonucleic acids and proteins are of critical importance to gene expression and may also connect it to cell metabolism in unexpected ways. We hypothesise that this is of particular importance in cardiac health and disease. We will employ the tools of proteomics and transcriptomics to characterise the topology and function of RNA-protein interaction networks in heart muscle cells, and thus contribute to the search for better treatment.
Do Transcription Factor-RNA Interactions Represent A New Mechanism Of Gene Regulation?
Funder
National Health and Medical Research Council
Funding Amount
$704,242.00
Summary
The aim of this proposal is to investigate the mechanisms through which genes are switched on and off. We hypothesise that transcription factors, a set of proteins that contacts DNA to regulate genes, can also interact with a separate class of molecules known as RNA. An understanding of how genes are switched on and off is central to devising strategies for fighting many diseases in a rational way. Our work will have implications for biotechnology and gene therapy.
The Characterisation Of An Essential Regulator Of Pre-mRNA Splicing Required For Germ Cell Function And Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$1,116,739.00
Summary
The male germ line is a fantastic system within which to define processes of fundamental importance to cell biology and health broadly. Within this grant we will define the role of a poorly described RNA splicing factor in all of stem cell function (spermatogonia), meiosis (spermatocytes) and in the remarkable metamorphosis underlying spermatid maturation. This will be done using a range of phenotypic characterizations, CHIP and RNA Seq technologies and gene sequencing.