STABILISING G PROTEIN-COUPLED RECEPTORS FOR DRUG DISCOVERY
Funder
National Health and Medical Research Council
Funding Amount
$628,140.00
Summary
Prescription drugs targeting human proteins called GPCRs are sold as effective treatments for many diseases. However, there are over 800 different types of GPCRs in the human body and only a small fraction is targeted by drugs, mainly because GPCRs are unstable and thus difficult to work with in the laboratory. We are applying newly developed technologies to engineer stabilised ?1-adrenoceptors, a class of GPCRs, for drug discovery against cardiovascular diseases, epilepsy and neurodegeneration
Novel Approaches To Understanding Peptide G-protein-coupled Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$665,043.00
Summary
G protein-coupled receptors (GPCRs) are proteins that exist on every human cell, where they sense, and respond to environmental stimuli. Because of their importance they are targeted by drugs to treat many diseases. However little is known about the molecular steps that underlie cellular responses upon drug binding and this has hindered new drug development. This project uses new technology to determine the complex pathway of GPCR activation upon drug binding which will aid new drug development.
Unravelling The Binding And Activation Mechanism Of A Complex G Protein-coupled Receptor
Funder
National Health and Medical Research Council
Funding Amount
$1,041,638.00
Summary
The peptide hormone relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as it can't be taken orally and is very expensive to produce. We will study the interaction of relaxin with its cell surface receptor and the mechanisms by which the receptor functions. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin for the treatment of heart failure
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.
Aspirin For The Prevention Of Cognitive Decline In The Elderly: A Neuro-Vascular Imaging Study (ENVIS-ion) From ASPREE
Funder
National Health and Medical Research Council
Funding Amount
$1,341,232.00
Summary
The ENVIS-ion trial will examine whether Aspirin is effective in delaying the onset of worsening of thinking and memory abilities in healthy older adults. Magnetic resonance imaging (MRI) of brain structure will detect markers of early worsening of thinking and memory abilities. Blood vessels in the back of the eye (retina) share many features with vessels in the brain. We will compare whether aspirin lessens changes over time of features shown with brain MRI and retinal photography.
Using Diffusion MRI For Understanding The Relationship Between Memory Decline And Corticothalamic Tracts
Funder
National Health and Medical Research Council
Funding Amount
$57,578.00
Summary
Stroke populations are at a risk of dementia. Structural changes have been demonstrated to precede cognitive changes, providing a potential for early diagnosis and intervention. Magnetic resonance imaging markers of structural connectivity are powerful predictors of dementia. As a longitudinal study, this proposal has the unique advantage that I will be able to detect changes in post-stroke brain networks in the 3 years after stroke. This raises the potential for future clinical application.
The Burden Of Late Preterm Birth On Brain Development And 2 Year Outcomes – A Prospective, Longitudinal Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$838,690.00
Summary
80% of preterm babies are born from 32-36 weeks’ gestation, and are late preterm (LPT). LPT children have more learning problems, but why this occurs is unknown. This study aims to understand the effect of LPT birth on brain development. We will do brain scans at term and assess development at 2 years of age of 200 LPT and 200 full-term children. We expect LPT babies will have subtle alterations in brain development compared with term controls which will be associated with delayed development.
Targeting Bone Marrow Lesions To Find Interventions In The Progression Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$467,395.00
Summary
It is essential to elucidate the underlying cause(s) of osteoarthritis because our current level of understanding of this condition has failed to produce effective treatments. Lesions in the bone under the cartilage (BMLs), seen using MRI, have strong potential value for the objective monitoring and management of OA. However, because the nature of BMLs is not well understood, the aim of this application is to perform a comprehensive study of BMLs in OA bone.
Epilepsy: Molecular Basis And Mechanisms In The Era Of Functional Genomics
Funder
National Health and Medical Research Council
Funding Amount
$12,062,533.00
Summary
The team comprises of neurologists with a special interest in epilepsy (both adult and child) molecular geneticists, physiologists and brain imaging specialists. The team leads the world in the discovery of the genetic causes of epilepsy and epilepsy associated with intellectual disability. The team will continue to identify the genes underlying epilepsy, and study how genetic variations result in the development of seizures and will continue to develop advanced imaging techniques for these stud ....The team comprises of neurologists with a special interest in epilepsy (both adult and child) molecular geneticists, physiologists and brain imaging specialists. The team leads the world in the discovery of the genetic causes of epilepsy and epilepsy associated with intellectual disability. The team will continue to identify the genes underlying epilepsy, and study how genetic variations result in the development of seizures and will continue to develop advanced imaging techniques for these studies. This will include extensive laboratory studies, including the development of mice with the exact mutations that we find in the human condition. Stateof-the-art imaging techniques with magnetic resonance and positron emission tomography are used in human subjects to further understand the effects of the mutations on the structure and function of the brain. This will allow deep understanding of how seizures develop and may lead to new diagnostic methods and treatments. The laboratory and clinical aspects of the research are tightly integrated in this internationally leading collaborative program.Read moreRead less