ATP Release From Gastrointestinal Epithelium: A Potential Target For The Treatment Of Slow Transient Constipation
Funder
National Health and Medical Research Council
Funding Amount
$317,775.00
Summary
Slow transit constipation (STC) is a severe condition of the colon, almost exclusively affecting reproductive age women with no effective treatment. We recently found an association between STC and defects in connexin proteins in the large intestine. We aim to reveal the role of connexins and female hormones in the maintenance of normal intestinal function and their involvement in STC. The study will provide completely new perspectives in the understanding of the functional bowel disorders.
Aurora Kinase: Molecular, Cellular And Functional Studies Deciphering Its Role In Stroke Injury
Funder
National Health and Medical Research Council
Funding Amount
$580,993.00
Summary
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating an enzyme called aurora kinase A (AURKA). We aim at unravelling (i) how AURKA is activated by oxygen deprivation, (ii) where the activated AURKA is localised in cells, and (iii) how the activated AURKA induces nerve cell death.The study will benefit development of therapeutic strategies to protect against brain damage in stroke since this is novel and different target for drug targeting.
Physiologically-based Pharmacokinetics And Pharmacodynamics Of Therapeutic Stem Cells For Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$848,710.00
Summary
This project focuses on the challenging area of effective and optimal dosing cell-based therapy for liver diseases. We will investigate the fate and therapeutic effects of natural, modified and artificial therapeutic cells in the body and in liver regions using a physiologically-based kinetic model. Our key goal is advance cell therapy by providing a better understanding and dosing guidelines.
Role Of The Drug Metabolising Enzyme Arylamine N-acetyltransferase 1 In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,196.00
Summary
The current project will identify the molecular mechanism(s) that underpins the significant changes in phenotype seen in a range of human cancer cells. The expected outcomes will be to demonstrate that NAT1 is critical for the clearance of pABG in cancer cells. The results will be important in the context of understanding this family of intracellular enzymes and will change the current thinking on the function of the arylamine N-acetyltransferase in normal and cancer cells.
Understanding Novel Drug Binding Pockets At G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$425,538.00
Summary
Cell-surface proteins exhibit multiple secondary binding sites for which only synthetic drugs have been identified so far. My hypothesis is that these secondary binding sites are common to most proteins because they are primarily targeted by largely yet unidentified endogenously released molecules that can modify the biology of these proteins.
Understanding The Function And Regulation Of G Protein-coupled Receptor Signalosomes And Their Role As High Resolution Signalling Platforms
Funder
National Health and Medical Research Council
Funding Amount
$566,588.00
Summary
G protein-coupled receptors are specialised proteins located on the surface of cells. They are the targets of 50% of currently available pharmaceuticals, but these drugs are derived from limited knowledge of only a fraction of proteins. This proposal will examine exciting and novel properties of receptors that only occur following the assembly of the proteins into specialised networks within cells. The new information will expand our current knowledge, and facilitate future targeted drug design.
Airway Smooth Muscle And Fixed Airway Obstruction: Strategies For Softening Muscle
Funder
National Health and Medical Research Council
Funding Amount
$555,643.00
Summary
In severe asthma the airways don't relax fully making breathing more difficult. The inability to relax is being addressed by exploring the behaviour of isolated muscle cells. These cells are able to compact collagen gels. The mechanisms used to compact the gel are different to those that cause rapid muscular contraction. We aim to identify the molecules responsible for the gel compaction as a first step to identifying new drugs to treat the fixed airway obstruction in severe asthma.
Resolving And Targeting The Complex Molecular Mechanisms Underlying GPCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,071,370.00
Summary
Receptors are located on the surface of all human cells to allow our cells to respond to their environment. Over 30% of prescription drugs act through particular receptors called GPCRs, however effective drugs without side effects are difficult to develop because we do not have a deep understanding of how GPCRs transmit complex signals. In this proposal we seek to resolve the atomic-level details of GPCR signalling to assist in the development of better drugs for a diverse range of diseases.