Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors ....Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors remains unknown. Our project will specifically investigate novel molecular mechanisms associated with serotonin receptor activity that may prove vital in understanding mechanisms of psychiatric illnesses, and how many psychiatric medicines actually work.Read moreRead less
Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not re ....Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not respond to the current TNF treatments. Improved anti-TNF strategies would provide enhanced health outcomes and welcome relief to many Australians. In addition, the economic benefit of the TNF market is very substantial. Therefore the potential impact of this research is very high both for health care and economical potential.Read moreRead less
Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monas ....Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monash University, will permit a rational, structure-based drug discovery platform to be established. The ultimate goal of this innovative and mutlidisciplinary approach, namely a portfolio of phase I therapeutics, will be of substantial benefit in the medical health area.Read moreRead less
Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotec ....Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotechnology company, Cytopia Ltd.Read moreRead less
Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these response ....Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these responses.Read moreRead less
Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by ....Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by implementing innovative approaches.
Expected Outcomes: Expected outcomes include significant new knowledge and a new multi-disciplinary platform for measuring peptide absorption.
Benefits: This should provide significant benefits by informing the future design of peptides for supplements, therapeutics and carriers. Read moreRead less
The cell biology of the albumin-FcRn receptor recycling system. The aim of this project is to define the cell biology of the albumin-FcRn (neonatal Fc receptor) recycling system. FcRn is a recycling membrane receptor that selectively protects serum proteins from intracellular degradation and prolongs their half-life. We will identify the key cell types involved in this recycling pathway, identify intracellular sites of ligand and FcRn interaction, assess the contribution of the haematopoietic sy ....The cell biology of the albumin-FcRn receptor recycling system. The aim of this project is to define the cell biology of the albumin-FcRn (neonatal Fc receptor) recycling system. FcRn is a recycling membrane receptor that selectively protects serum proteins from intracellular degradation and prolongs their half-life. We will identify the key cell types involved in this recycling pathway, identify intracellular sites of ligand and FcRn interaction, assess the contribution of the haematopoietic system and determine ligand half-life in mice. Findings generated will reveal the basic biology of an important physiological receptor, and enable the exploitation of FcRn-receptor interactions for design of recombinant albumin fusion-based therapies.Read moreRead less
Enhancing fertility for the Thoroughbred and Standardbred industries. Enhancing fertility for the Thoroughbred and Standardbred industries. Responding to industry calls for improved methods of detecting and managing infertility in both stallions and mares, this project aims to provide a platform for competitive collaborations between universities, biotechnology companies and horse breeders: the end-users of technological developments in equine reproduction. The Thoroughbred and Standardbred bree ....Enhancing fertility for the Thoroughbred and Standardbred industries. Enhancing fertility for the Thoroughbred and Standardbred industries. Responding to industry calls for improved methods of detecting and managing infertility in both stallions and mares, this project aims to provide a platform for competitive collaborations between universities, biotechnology companies and horse breeders: the end-users of technological developments in equine reproduction. The Thoroughbred and Standardbred breeding industries contribute over $6.5 billion per annum to the Australian economy and employ thousands of staff across their value chains. However, these industries suffer from breeding program inefficiencies that amount to over $800 million in annual losses. Expected outcomes are novel reproductive technologies and specialised research capabilities that will make the Australian equine industry a global leader.Read moreRead less
Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host ....Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host parasite interactions which may in turn suggest novel approaches or pathways to persue. This may eventually lead to the development of novel therapeutics.
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New approaches for screening cereal germplasm for enhanced microbial pathogen resistance and desirable grain texture. The trait of grain hardness (texture) is of significance to the Australian infrastructure, as exports of hard wheat contribute over 5 billion dollars per year on average to the national economy and hard wheats are also important for domestic usage. The genes responsible for grain texture also impart resistance to bacterial and fungal pathogens which can cause extensive damage. ....New approaches for screening cereal germplasm for enhanced microbial pathogen resistance and desirable grain texture. The trait of grain hardness (texture) is of significance to the Australian infrastructure, as exports of hard wheat contribute over 5 billion dollars per year on average to the national economy and hard wheats are also important for domestic usage. The genes responsible for grain texture also impart resistance to bacterial and fungal pathogens which can cause extensive damage. However, the Australian gene pool has very limited genetic diversity in grain textures and thus possibly in pathogen resistance. The project will work out the science behind these two traits and identify lines with new variants of textures and pathogen resistances, thus greatly benefiting the national infrastructure and local primary industries.Read moreRead less