Targeting Protein Kinase C In Diabetes Management Using Novel Polyunsaturated Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
PKC regulates a diverse range of cellular processes in an isozyme-specific manner. There is strong recent evidence to implicate PKC, especially PKC _, in mediating the actions of glucose in diabetes. This includes the action of glucose in renal glomeruli, retina, aorta and heart of diabetic animals and in cultured cells from these organs. More importantly, inhibition of PKC_ with the PKC_-specific inhibitor, LY333531, blocks the actions of glucose. Recently, our research group designed and synth ....PKC regulates a diverse range of cellular processes in an isozyme-specific manner. There is strong recent evidence to implicate PKC, especially PKC _, in mediating the actions of glucose in diabetes. This includes the action of glucose in renal glomeruli, retina, aorta and heart of diabetic animals and in cultured cells from these organs. More importantly, inhibition of PKC_ with the PKC_-specific inhibitor, LY333531, blocks the actions of glucose. Recently, our research group designed and synthesised a family of novel polyunsaturated fatty acids. One of these, MP5 (_-oxa- 21:3n-3), inhibited high glucose-induced activation of PKC? in cultured mesangial cells as well as in glomeruli of diabetic rats in a relatively selective manner. The overall aim of this proposal is to evaluate the potential for a chemically engineered novel polyunsaturated fatty acid, MP5 (_-oxa-21:3n-3), to treat pathogenesis associated with diabetes by targeting the PKC system. The specific aims are to: 1. Characterise the effects of MP5 on glucose- or advanced glycosylation end product-stimulated activation of protein kinase C (PKC). 2. Determine whether esterification of MP5 into diacylglycerol is essential for the action of MP5 3. Investigate whether MP5 is efficacious at preventing the actions of glucose in vitro e.g. glucose stimulated TGF_ production in mesangial cells, and in vivo in streptozotocin-diabetic rRead moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100985
Funder
Australian Research Council
Funding Amount
$409,574.00
Summary
Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes wit ....Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes with high efficacy and specificity. This project will provide new and intriguing insights into cellar function, with broad applications in basic research and biotechnology.Read moreRead less
A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability ....A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability of current drugs and thus significantly shorten the recurrence period. Such new drugs may have broad applicability.Read moreRead less
The first integrated multimodal assay for the ultrasensitive detection of dengue contamination of blood. This project will develop the first screening test to check for dengue contamination of blood donations in Australia. This will help ensure safe, continued supply from blood donors, particularly in Queensland where dengue is on the rise.
Targeting the delivery of cytotoxic agents to tumour cells using novel minicells as drug delivery vehicles and engineered, bispecific antibodies. Cancer persists as a major cause of morbidity and mortality globally. A major problem is the non-specific action of drugs used for treatment. The minicell is a drug delivery vehicle, capable of packaging a variety of drugs. The project will develop tumour-specific antibodies that will target minicells to tumours, improving cancer survival rates.
Intracellular trafficking and function of a recycling receptor which prolongs the serum half-life of novel therapeutic proteins. The life span of recombinant engineered proteins for therapeutic use is a critical factor in their effectiveness, ease of clinical application and cost. This project will exploit interactions with a natural receptor, which prolongs the lifespan of serum proteins, to enhance survival of therapeutic engineered proteins.