Pharmacological Regulation Of Airway Smooth Muscle Phenotype
Funder
National Health and Medical Research Council
Funding Amount
$276,742.00
Summary
In Australia there is a high incidence of asthma which impairs quality of life and can sometimes cause death if sufficiently severe. The main cause of asthma is the shortening of muscle surrounding the airway passages that cause the narrowing of these tube-like passages. When airway passages narrow a feeling of chest tightness is perceived by the asthmatic patient. When the narrowing is severe the amount of oxygen being delivered to the blood can be reduced to dangerous levels. When there is mus ....In Australia there is a high incidence of asthma which impairs quality of life and can sometimes cause death if sufficiently severe. The main cause of asthma is the shortening of muscle surrounding the airway passages that cause the narrowing of these tube-like passages. When airway passages narrow a feeling of chest tightness is perceived by the asthmatic patient. When the narrowing is severe the amount of oxygen being delivered to the blood can be reduced to dangerous levels. When there is muscle growth in the airways even small amounts of shortening of the muscle can cause severe narrowing of the airway passages. This research will investigate how muscle grows in asthmatic airways and look for new ways to use drugs to treat this muscle growth. We hope to improve drug treatment of asthma by limiting the amount of airway narrowing caused by muscle contraction.Read moreRead less
New Dopaminergic Neurons In The Parkinson's Disease Striatum: Establishment Of Phenotype, Function And Origin.
Funder
National Health and Medical Research Council
Funding Amount
$156,493.00
Summary
Parkinson s disease is usually associated with loss of dopamine cells that send nerves from the substantia nigra to the striatum. However, we have found large numbers of apparently new dopaminergic cells in post mortem tissue from the striatum of 10 patients with Parkinson s disease but not in 5 age-matched controls. Our aims are firstly to determine whether these cells are indeed dopaminergic neurons by establishing their neurochemical and morphological profiles. This is required to determine w ....Parkinson s disease is usually associated with loss of dopamine cells that send nerves from the substantia nigra to the striatum. However, we have found large numbers of apparently new dopaminergic cells in post mortem tissue from the striatum of 10 patients with Parkinson s disease but not in 5 age-matched controls. Our aims are firstly to determine whether these cells are indeed dopaminergic neurons by establishing their neurochemical and morphological profiles. This is required to determine whether these apparently dopaminergic cells do indeed produce the neurotransmitter dopamine and to determine to what class of neuron they belong. The latter is important to establish whether they act locally in the striatum or extend their influence over a larger area of the brain. Secondly we shall assess their function in human and rat tissue. We shall determine whether their number is related to the severity of damage in Parkinson s disease, or whether L-DOPA therapy, which most patients receive, plays any role in their appearance. These experiments will lay the ground work to allow us to determine whether these cells are beneficial or harmful. Lastly, we shall determine where these cells come from. We shall determine whether they have always been present but have taken on a new function, or whether they are in fact new cells which have been born recently. This knowledge is essential if we are to be able to change their numbers to improve treatment of Parkinson s disease. We estimate that there are up to 66,000 of these dopaminergic cells in each striatum of patients with Parkinson s disease. This is enough to have a significant impact on the manifestation of the disease. These cells might be beneficial, allowing the brain to maintain essential functions for longer or they might be harmful playing a role in either development of Parkinson s disease itself or the harmful side effects of L-DOPA therapy.Read moreRead less
The Role Of Novel And Essential Bromodomain Proteins In Coordinating Malaria Parasite Gene Regulation And Their Potential As Anti-malarial Targets
Funder
National Health and Medical Research Council
Funding Amount
$689,034.00
Summary
Malaria kills over 400,000 people a year and new therapies are needed. Malaria parasites activate groups of genes by novel mechanisms that could be targeted by drugs. We will characterise a novel group of proteins to identify those that activate genes essential for parasite survival. We will also search for molecules that inhibit the proteins and kill malaria parasites. Thus we will discover how parasites control their genes and identify drug targets and inhibitors for drug development.
Immune Regulation During Uncomplicated And Severe P. Falciparum And P. Vivax Malaria
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
Malaria is a major global disease that kills over 1 million people every year. Immune responses induced during infection help fight the infection but can also cause tissue damage and thereby worsen disease. This study will determine differences in cellular immune responses during uncomplicated and severe malaria. Better understanding of the role of immune cells in response to infection and disease progression will assist the development of novel treatment interventions and vaccine development.
Blood clotting is dependent upon platelets. A decline in platelet number, or thrombocytopenia, is a life threatening condition that can result from various diseases or importantly as a side effect of chemotherapy. We are investigating the control of platelet production. A long term goal is to stimulate platelet production in patients by boosting the natural pathways or to generate platelet producing cells for transfusion from a patient's own skin cells by genetic reprogramming.
Unravelling The Impact Of An Energy-rich Environment On Susceptibility And Resistance To Obesity
Funder
National Health and Medical Research Council
Funding Amount
$796,754.00
Summary
Obesity in Australia is at a crisis point. It is clear that energy-rich environments and an individual’s genes leads to excessive weight gain, but what we don’t understand is why some individuals are more prone to this than others. Comprehending this biological regulation is imperative if we are to develop more effective drug or dietary treatments to abate this disease. Thus it is the aim of this grant to dissect the biological/genetic/possible epigenetic perturbations leading to common obesity.
Identification Of The Conformation Dependant Targets Of Autoimmune Disease Linked Variation In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,001,815.00
Summary
Specialised immune cells called regulatory T cells act as the policemen of the immune system, preventing the immune system attacking itself, but still fighting infections. If these cells do not work properly, autoimmune diseases such as type 1 diabetes or IBD can arise, because of immune attack on normal body tissue by mistake. In order to explain how this goes wrong we need to carefully identify all of the gene interactions in these cells including interactions over long distances in the DNA.