Understanding The Role And Mechanism Of Interaction Of Small Heat-shock Proteins In Age-related Disease
Funder
National Health and Medical Research Council
Funding Amount
$270,827.00
Summary
Protein precipitation is associated with a diversity of age-related diseases such as cataract and Alzheimer's. Within cells, a group of chaperones called the small heat-shock proteins (sHSPs) function by binding to destabilized proteins, however, common in vivo modifications can disrupt their cellular role leading to co-aggregation in a number of age-related diseases. This study will use state of the art mass spectrometry to examine the mechanism by which sHSPs interact with client proteins.
Distribution Of Monodisperse Aerosols Inhaled By Children For Determination Of Optimal Therapeutic Inhaler Formulations
Funder
National Health and Medical Research Council
Funding Amount
$326,000.00
Summary
Inhalers are the primary form of treatment for asthma, allowing the delivery of lower doses of medication directly to the lungs. Consistent daily use of these inhalers is often necessary to effectively control the symptoms of asthma. Inhalers are now increasingly used to treat infants with lung problems. Many of these inhalers are not designed for use by such young children, who may be unable to perform the breathing techniques necessary for effective use of these inhalers. Not all the drug inha ....Inhalers are the primary form of treatment for asthma, allowing the delivery of lower doses of medication directly to the lungs. Consistent daily use of these inhalers is often necessary to effectively control the symptoms of asthma. Inhalers are now increasingly used to treat infants with lung problems. Many of these inhalers are not designed for use by such young children, who may be unable to perform the breathing techniques necessary for effective use of these inhalers. Not all the drug inhaled by patients will end up in the lungs where it is needed; a large proportion is left in the mouth, throat and stomach. Our earlier studies have shown that there is a large amount of variability in the amount of drug received by children using inhalers. We intend to assess the important factors involved in improving the efficiency of inhaler therapy for children, such as the size of the inhaled particles and the breathing pattern of the child. The results obtained from this study will enable us to determine the best method of delivering these drugs to children so that they only receive the lowest effective dose for treatment of the symptoms of asthma while minimising unwanted effects.Read moreRead less
Intravascular Leukocyte Trafficking During Thromboinflammation
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Unblocking blood vessels to treat heart attack and stroke can unfortunately cause a paradoxical worsening of organ damage, due to increased inflammation upon blood flow restoration. We have identified a novel way in which this side-effect is regulated by the small blood clotting cells platelets, and the protein fibrin. We will investigate ways to reduce the pro-inflammatory role for platelets, and define safer clot busting treatments.
In Vitro And In Vivo Assessment Of The Funhaler -an Innovative Therapeutic Device For Children
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler ....Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler incorporates a spinning toy attached to the outside of the spacer. The toy is activated when the patient breathes through the spacer. The device has been designed to encourage children to co-operate when their asthma therapy is being delivered. The Funhaler is currently in the late development stage. We propose, firstly, to carry out in vitro assessments of drug delivery from the Funhaler compared to the two most widely available small volume spacers: the Aerochamber Plus (Trudell, Canada) and the Breath-A-Tech (Scott-Dibben, Australia). These assessments will be carried out to meet the standards of regulatory bodies worldwide (including the FDA). Secondly, we propose to perform extensive in vivo studie: filter studies to assess drug delivery to the patient; deposition studies to measure drug deposition in the lungs; and a pilot clinical trial to assess the efficacy of the device during medium to long-term use in children aged 2-8 years.Read moreRead less
The Role Of The Plasminogen Activators (PAs), Urokinase-PA And Tissue-type PA In Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA ( ....Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA (u-PA) and tissue-type PA (t-PA) convert plasminogen into plasmin which can then breakdown the accumulated fibrin. Their presence in RA patients would therefore be beneficial. However, u-PA is also implicated in cell migration leading to inflammatory cells accumulating in the joint, and cartilage destruction, both of which are detrimental to disease outcome. In the joints of RA patients there are high levels of u-PA and low levels of t-PA. We, and our collaborators, have found that in the absence of t-PA, disease is exacerbated, whilst in the absence of u-PA, the outcome depends on the type of disease, either exacerbating or ameliorating disease. This highlights the different roles u-PA can have. The current proposal aims to determine the role of u-PA in inflammation and arthritis, and whether enhancing t-PA can have beneficial outcomes with respect to disease severity. In addition, we will also study whether intra-articular fibrin deposition can, in fact, drive the inflammatory reaction and cartilage destruction seen in RA. The findings will be important for our understanding of the role of fibrin accumulation in the inflammatory and destructive processes that occur in RA, and the roles of u-PA and t-PA in enhancing and preventing them respectively. Information gained will provide clues for useful strategies for the treatment of human inflammatory diseases, including RA.Read moreRead less
Role Of Hsp40 And Hsp70 In Huntingtin Misfolding, Oligomerization And Inclusion Assembly
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
Huntington disease results from a mutation that causes the Htt protein to become abnormally sticky and form toxic clusters in neurons. Cells have natural defences to clustering with proteins called chaperones, which are exciting therapeutic targets. This project will examine how chaperones defend against toxic Htt clustering with cutting-edge imaging technologies. The knowledge gained will aid in designing therapeutic strategies that stimulate the defence processes and suppress the clusters.
Understanding And Preventing Airborne Transmission Of Infectious Respiratory Aerosols
Funder
National Health and Medical Research Council
Funding Amount
$393,894.00
Summary
This project aims to significantly advance our understanding of how infectious bacteria are transmitted through the air, and what basic control measures are most effective at preventing this. This research is focused on persons with cystic fibrosis (CF), as they may be particularly susceptible to such transmission, but our results will also help us better understand how other infections are spread through the air. This is especially important given the recent global influenza pandemic.
The Role Of Huntingtin Misfolding And Oligomerization In Huntingtons Disease
Funder
National Health and Medical Research Council
Funding Amount
$474,329.00
Summary
Mutations in the huntingtin gene cause Huntington's disease by making the gene product aggregate together into non-normal and different sized polymers. However, it is not understood how this process causes cells to die, largely because we don't understand how the abnormal forms accumulate in cells over time. We will examine where in cells the abnormal shapes accumulate and how they cause toxicity. This research will identify critically-needed therapeutic targets against Huntington's disease.