Structural Investigation Of The Major Histocompatibility Complex Class I Peptide-loading Complex
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
The identification and destruction of diseased cells by our immune system is essential to controlling the spread of infection. This proposal is aimed at the characterisation of the peptide-loading complex (PLC), a large molecular machine that facilitates a crucial step in the process of ‘flagging’ infected cells. Determining the 3D structures of its key components, as well the way in which they interact will help us understand how the PLC contributes to maintaining our body’s health.
THE BIOLOGY OF HUMAN DEC-205: A POTENTIAL ANTIGEN LOADING RECEPTOR FOR DENDRITIC CELLS
Funder
National Health and Medical Research Council
Funding Amount
$227,017.00
Summary
Dendritic Cells (DC) represent a unique subset of white blood cells which play a critical role in initiating the immune response. Foreign material from bacteria-viruses and potentially cancer cells are recognised by DC, taken inside, processed and presented with other signals to T and B Lymphocytes for a response. Several DC surface molecules may beinvolved in the recognition of foreign material. We have cloned human DEC-205, a molecule which is predicted to bind the sugar groups associated with ....Dendritic Cells (DC) represent a unique subset of white blood cells which play a critical role in initiating the immune response. Foreign material from bacteria-viruses and potentially cancer cells are recognised by DC, taken inside, processed and presented with other signals to T and B Lymphocytes for a response. Several DC surface molecules may beinvolved in the recognition of foreign material. We have cloned human DEC-205, a molecule which is predicted to bind the sugar groups associated with bacteria-viruses and to act as a foreign material recognition and loading receptor. This project seeks to synthesise components of DEC-205 to test the binding capacities of its different components to different sugars and other molecules. We will also establish its expression pattern and how this is regulated on different white blood cell types. It is also possible that DEC-205 transmits signals which activate the DC, and we will test for that possibility. Finally, we will attempt to exploit this knowledge for loading cancer target molecules into DC via DEC-205 to initiate a cancer vaccine response.Read moreRead less
The Effect Of Loading On The Size, Shape And Strength Of Cortical Bone During Different Stages Of Maturation
Funder
National Health and Medical Research Council
Funding Amount
$180,000.00
Summary
Osteoporosis is a condition in which the skeleton becomes fragile and susceptible to fractures. It is a public health problem that affects both men and women over the age of sixty. Although osteoporosis affects the elderly, the most opportune time to prevent osteoporosis may be during childhood. Physical activity is a lifestyle factor known to affect the strength of the skeleton. Bone density is commonly used as a measure of bone strength because it is easily measured and is related to the break ....Osteoporosis is a condition in which the skeleton becomes fragile and susceptible to fractures. It is a public health problem that affects both men and women over the age of sixty. Although osteoporosis affects the elderly, the most opportune time to prevent osteoporosis may be during childhood. Physical activity is a lifestyle factor known to affect the strength of the skeleton. Bone density is commonly used as a measure of bone strength because it is easily measured and is related to the breaking strength of bones. However changes in the shape of bones can also affect bone strength with or without an increase in bone density. Changes in bone shape in response to exercise in children or adults have rarely been investigated, and little is known about the effects of exercise on bone shape during different stages of growth. This study is the first to investigate how exercise during childhood may affect bone strength by changing bone shape. 45 elite female tennis players aged between 6 to 18 years have completed two years of this study. 90 novice and competitive male tennis players aged between 6 to 20 years and 60 healthy age matched controls will be asked to participate in this study. Measurements will be made annually for three years. The bone shape and density of the dominant and non-dominant arms of the players will be compared with the children who don't play tennis - comparisons will also be made between i) different stages of puberty and ii) girls and boys. The findings of this study are important because the lifestyle of children today may predispose them to a greater risk of osteoporosis late in life. Physical activity may be the most important modifiable protective factor against fragile bones in old age. The findings of this study will be the first to provide insight into whether there is a unique time during growth when exercise will result in the greatest increase in bone strength by changing bone shape.Read moreRead less
The Molecular Basis Of HLA-linked Drug Hypersensivity Reactions
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used ....Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used pharmaceutical.Read moreRead less
Understanding The Complexity Of Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
I have developed and established the use of mass spectrometry to identify and quantitate ligands of antigen presenting molecules to understand the breadth of immune responses in a variety of human disease states including autoimmunity, cancer, infection and allergy. By embedding the technology in disease focussed research programs I will define the molecular bases of these diseases and the important immunological targets that will provide new avenues for therapeutic development and vaccines.