GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
Se015: A Developmental Drug For The Treatment Of Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$304,206.00
Summary
Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with ....Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with disease progression. Nearly all therapies that have shown some efficacy in treating cancer, such as chemotherapy and radiation have a mode of action whereby they attempt to kill cancer cells by inflicting enough damage to the cancer cells that they induce them to commit cell suicide, a process called apoptosis. Unfortunately, cancer cells can become resistant to these therapies by activating the cells' own signaling pathways that normally block apoptosis. One of the key pathways that has been implicated in resistance to apoptosis in human cancers is the PI3K-Akt pathway. This pathway is overactivated in many advanced human tumors, particularly in glioblastoma. We have discovered a compound, Se015, which can effecitively block this pathway in brain cancer cells and is able to dramatically improve the effectiveness of both chemotherapy and radiation in killing these cells. We have confirmed the efectiveness of Se015 in preliminary animal models of brain cancer, where we have shown that Se015 demonstrated no noticeable toxicity and was active when taken orally. We now need to explore further the molecular mode of action of Se015, as well as complete our animal studies with the eventual aim of initiating a small trial of Se015 in glioblastoma patients in the forseeable future.Read moreRead less
Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertake ....Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertaken. We anticipate that the product will be of major commercial interest. We will further explore what is a rapidly expanding marketplace and ensure we maximize the commercial return on this product.Read moreRead less
A New Non-invasive Diagnostic Technique Based On Detection Of Exhaled Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$179,300.00
Summary
We developed a special collection mask and showed that the breath of people with colds or flu contains a tiny amount of virus. Currently, diagnostic samples are collected by putting a tube into the airways - this is very uncomfortable. Our masks may provide a new and more comfortable way to diagnose lung infections. We want to build better masks and ways to detect viruses and bacteria to test out this method. This may create a new test that will improve diagnosis and treatment.
An Inside-out Approach To Muscosal Vaccination: MAdCAM Targeting
Funder
National Health and Medical Research Council
Funding Amount
$174,250.00
Summary
The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the ....The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the gut (called MAdCAM) so that the vaccine is linked to an antibody against MAdCAM. Thus for the first time we believe that a parenteral vaccine ie. injected im or iv (bypassing the oral barriers) can induce mucosal immunity.Read moreRead less
Development Fo A Novel Treatment For Asthma: The Identification Of Lead Small Molecule Antagonists Of The IL-13/IL-13 Re
Funder
National Health and Medical Research Council
Funding Amount
$99,750.00
Summary
In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagoni ....In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagonists of IL-13Ra1 and to identify those suitable for development as novel asthma therapeutics.Read moreRead less
Developing Anti-Inflammatory Drugs Based On Inhibition Of A Human Enzyme
Funder
National Health and Medical Research Council
Funding Amount
$160,000.00
Summary
Human secretory phospholipases A2 have been associated with inflammatory diseases for many years, yet very few truly potent inhibitors of the human enzymes sPLA2 (isoforms IIa, V or X) are known due to a range of problems relating to the lipid nature of substrates, unavailability of enzymes, enzyme assays that do not correlate with in vivo data. Although there remains controversy about which enzyme is responsible in vivo for degrading membrane phospholipids to inflammatory mediators like arachid ....Human secretory phospholipases A2 have been associated with inflammatory diseases for many years, yet very few truly potent inhibitors of the human enzymes sPLA2 (isoforms IIa, V or X) are known due to a range of problems relating to the lipid nature of substrates, unavailability of enzymes, enzyme assays that do not correlate with in vivo data. Although there remains controversy about which enzyme is responsible in vivo for degrading membrane phospholipids to inflammatory mediators like arachidonate, PAF, prostaglandins, leukotrienes, etc. there is a consensus that blockade of phospholipid metabolism would represent a major advance on NSAIDs as antiinflammatory agents. No sPLA2-IIa inhibitor is available yet in man. We aim to create an attractive data package showing proof of concept for a potent new type of antiinflammatory drug. This data will give us an improved negotiating position in our commercialisation of a new drug with potential multi-billion dollar markets as diverse as arthritis, asthma, reperfusion injury, organ transplantation and many other currently intractable human ailmentsRead moreRead less
Novel Methods For Promoting Organ Development And Growth
Funder
National Health and Medical Research Council
Funding Amount
$390,203.00
Summary
A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of Colony Stimulating Factor (CSF-1). We have evidence that CSF-1 therapy can promote kidneys and lungs to continue development and maturation after birth. This exciting new finding allows for the application of CSF-1 therapy for both the treatment of premature babies and unborn babies with kidney defects.
Development Of Resonance Energy Transfer Technologies To Detect GPCR Heterodimer Complexes In Living Cells
Funder
National Health and Medical Research Council
Funding Amount
$205,555.00
Summary
G-protein coupled receptors are proteins at the surface of most cells in the body. They bind to drugs, transmitting signals into cells that change what cells are doing. Recent research indicates that different types of these proteins can interact with each other and when one of these protein combinations binds a drug, it acts differently to when the proteins act separately. The aim of our project is to find out which protein combinations exist and to find drugs that bind to them specifically.
Novel Soluble Guanylate Cyclase Activators For Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$474,087.00
Summary
Pulmonary hypertension (elevated blood pressure in the lungs) is a life-threatening condition with few treatment options. We have recently identified a new class of drug that may improve blood vessel function in the lungs and thereby provide a new drug for the management of this group of patients.