Mechanism Of Signal Transduction And Receptor Activation In Ligand Gated Ion Channel Receptors
Funder
National Health and Medical Research Council
Funding Amount
$551,560.00
Summary
This project seeks to provide fundamental new information about the means by which neurotransmitter receptors, which mediate fast synaptic neurotransmission, operate. This knowledge is important since the Cys-loop family of ligand gated ion channel receptors are responsible for a wide range of neuronal signalling and the control of both excitatory and inhibitory receptors. The Cys-loop receptors are modulated by both therapeutic drugs (eg. benzodiazepines, barbiturates, antiemetics) and by recre ....This project seeks to provide fundamental new information about the means by which neurotransmitter receptors, which mediate fast synaptic neurotransmission, operate. This knowledge is important since the Cys-loop family of ligand gated ion channel receptors are responsible for a wide range of neuronal signalling and the control of both excitatory and inhibitory receptors. The Cys-loop receptors are modulated by both therapeutic drugs (eg. benzodiazepines, barbiturates, antiemetics) and by recreational drugs (eg. alcohol, nicotine). They are also targets for development of new therapeutic drugs, such as allosteric modulators of nAChR for memory enhancement, or modulating GlyR to relieve spasticity or chronic pain. The project will use a range of molecular advances made by this and other laboratories to clarify how neurotransmitters enable their receptors to activate and signal. This fundamental information is of major medical significance as defective synaptic transmission, caused by mutations in ligand gated ion channel receptors, gives rise to a number of neurological and psychiatric disease states. The ligand gated receptors are also major targets for therapeutic drugs and the information gained in this study may also provide insights into new ways in which drugs could be used to enhance or inhibit synaptic signalling.Read moreRead less
How Do Glycosaminoglycans Promote The Propagation Of Prions?
Funder
National Health and Medical Research Council
Funding Amount
$512,270.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major c ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major component of purified prions is an abnormal disease associated form of the host encoded prion protein. Understanding how the disease associated form of the prion protein is generated and how host-derived cofactors contribute to its formation will help in our understanding of the infectious nature of these diseases and in the development of effective therapeutic and prophylactic strategies. Glycosaminoglycans are host-derived components of the extracellular matrix that are associated with prion protein plaques found in the brain tissue of patients with prion diseases. Glycosaminoglycans are believed to influence the transmission of prions and the ongoing propagation of infectivity. In this study the importance of glycosaminoglycans in the formation of the disease associated prion protein and the generation of infectivity will be investigated using both cell-free and cell-based models of prion propagation. The understanding gained from this study will be used to develop a high throughput assay that can be used to detect prion infection prior to the development of clinical disease and within a time frame whereby therapeutic intervention may be effective.Read moreRead less
Infrared Spectroscopic Imaging In The Diagnosis Of Cervical Cancer
Funder
National Health and Medical Research Council
Funding Amount
$291,600.00
Summary
In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to pro ....In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to probe smears shows promise in providing such an easily automated reliable method. We, and others have spent a number of years exploring this technique and have solved a number of the problems associated with it. Based on our work in the field and the work of others we now wish to develop a methodology using an infrared micro-imaging spectrometer combined with multivariate statistics that can be used to diagnose cervical cancer and the conditions that lead to cervical cancer.Read moreRead less
Detailed Investigation Of The Humoral Immune Response To HCV To Identify Diagnostic And Prognostic Serological Markers
Funder
National Health and Medical Research Council
Funding Amount
$387,466.00
Summary
The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the d ....The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the different stages of infection. The expected outcomes of this study include the identification of a marker of recent Hepatitis C infection. This will permit accurate epidemiological monitoring of Hepatitis C, better design of programs to control the spread, trace outbreaks and manage treatment programs. The identification of a marker capable of predicting the clinical outcome of infection would be invaluable to clinicians, because following acute infection with Hepatitis C, 20 to 30% of individuals will resolve their infection without the need for therapeutic intervention. The information obtained in this study will also lead to a better interpretation of diagnostic laboratory findings, improving our ability to provide clear and accurate reports to blood donors and consequently enhance the Australian blood supply in terms of safety and donor retention.Read moreRead less