Apical Membrane Proteins As Targets For A Schistosomiasis Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$480,459.00
Summary
Schsitosomiasis is a chronic neglected tropical disease for which there is currently no vaccine. A vaccine is sorely needed to control this parasite. This proposal seeks to identify molecules from the outer surface of the parasite which are recognised by the immune system of people from Brazil who are resistant to schistosomiasis. Molecules identified in this manner will be tested as vaccines in an animal model of schistosomiasis, and ranked based on their performances to enter human trials.
Translational Control Of Gene Expression And The Choice Between Cell Death And Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$378,000.00
Summary
Proteins carry out most enzymatic and structural functions in a cell. Thus, the kinds of protein molecules that are found in a given cell determine its characteristics and cells respond to changes in their environment by adjusting the abundance of some or many proteins in their collection. The instructions for the assembly of proteins are encoded in the genes and this information is expressed via intermediary molecules called messenger (m)RNA. Both, transcription of the genes into mRNA molecules ....Proteins carry out most enzymatic and structural functions in a cell. Thus, the kinds of protein molecules that are found in a given cell determine its characteristics and cells respond to changes in their environment by adjusting the abundance of some or many proteins in their collection. The instructions for the assembly of proteins are encoded in the genes and this information is expressed via intermediary molecules called messenger (m)RNA. Both, transcription of the genes into mRNA molecules and their subsequent translation by the ribosomes into protein are tightly controlled steps in the gene expression pathway. Erroneous gene expression is a major factor in human disease and dysregulation of translation is linked to a growing spectrum of illnesses such as cancer and cardiovascular disease, viral infection, and less frequent hereditary syndromes. The project proposed here is prompted by emerging evidence for a role of translational regulation in controlling the balance between cell death and survival. Tipping this balance has disastrous consequences for an organism as evidenced by its involvement in many major disorders (e. g. stroke, heart failure, neurodegeneration, AIDS, cancer, autoimmunity). Our aim is to test the hypothesis that a putative translational regulator termed p97-DAP5-NAT1, and a specialised mechanism of translation initiation by internal ribosome entry are important for the maintenance of this balance. To investigate this, we will employ DNA chips, a novel tool from Genomics research that allows the measurement of the levels of thousands of mRNA molecules in a single experiment. It is conceivable that knowledge of these special mechanisms of translation will lead to novel targets for therapeutic intervention, and this work will contribute some of the experimental tools to explore these avenues in the future.Read moreRead less
Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for i ....Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for integrating nuclear actions that has the potential to create a signal transduction circuit triggered by environmental or genetic factors. This information is crucial in defining the molecular logic of signalling events that may be ultimately targeted to control cell growth, differentiation and survival.Read moreRead less
Understanding The Molecular Heterogeneity Of Response And Resistance To Anti-HER2-ErbB2 Agents In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$373,173.00
Summary
A revolution in cancer care will take place in the next decade as we aim to individualize treatment for each patient. A subtype of breast cancer relies on a growth factor called HER2 for growth. Treatments that block HER2 are highly effective and have less side effects than chemotherapy. My study aims to further understand of the biology of this subtype of breast cancer and action of anti-HER2 agents as this will allow us to treat this aggressive type of breast cancer more effectively.
Novel Strategies For The Early Identification Provention And Treatment Of The Microvascular Complications Of Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$4,715,000.00
Summary
Despite recent advances, approximately one third of subjects with type 1 diabetes develop kidney disease and similar proportion develop vision-threatening eye disease. Indeed, in many instances eye and kidney disease occur in the same individual. The central aim of this proposed Special Program is the exploration of mechanisms that lead to the development and progression of these devastating complications of type 1 diabetes with a particular focus on novel strategies, directly applicable to man, ....Despite recent advances, approximately one third of subjects with type 1 diabetes develop kidney disease and similar proportion develop vision-threatening eye disease. Indeed, in many instances eye and kidney disease occur in the same individual. The central aim of this proposed Special Program is the exploration of mechanisms that lead to the development and progression of these devastating complications of type 1 diabetes with a particular focus on novel strategies, directly applicable to man, for their prevention and treatment. Participants in Special Program include both established diabetes researchers and investigators from other areas of academia (blood vessel biology and applied genetics). Strong interrelationships between the various investigators and their departments already exist and will be further consolidated with continued collaboration, sharing a combination of models, novel interventions and complex genetic techniques that would not be possible outside of a large collaborative framework. In addition to academic collaboration, interactions with industry-based drug discovery programs is also an important component in developing new treatment strategies for diabetic kidney and eye disease. The Special Program will thus consist of a range of studies of direct relevance to diabetic kidney and diabetic eye disease in humans. It is expected that these studies will lead to new strategies for the prevention, treatment and even the reversal of long term complications of diabetes.Read moreRead less