We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Industrial Transformation Training Centres - Grant ID: IC170100022
Funder
Australian Research Council
Funding Amount
$4,420,408.00
Summary
ARC Training Centre for Innovative BioEngineering. The ARC Training Centre for Musculoskeletal Biomedical Technologies will provide the next-generation of skilled graduates to overcome industry-focused challenges in musculoskeletal regeneration. The Centre expects to engineer a set of integrated technologies to personalise implants for the unique biological, physical and lifestyle characteristics of the recipient. Expected outcomes of the Centre include embedded bioelectronic sensors to assess a ....ARC Training Centre for Innovative BioEngineering. The ARC Training Centre for Musculoskeletal Biomedical Technologies will provide the next-generation of skilled graduates to overcome industry-focused challenges in musculoskeletal regeneration. The Centre expects to engineer a set of integrated technologies to personalise implants for the unique biological, physical and lifestyle characteristics of the recipient. Expected outcomes of the Centre include embedded bioelectronic sensors to assess and optimise the healing process. In addition, the Centre will produce data for use in deriving the next-generation of implants, giving rise to improved health outcomes, economic benefits, and a skilled workforce able to advance and perpetuate this important field.Read moreRead less
Endocrine And Molecular Regulation Of Placental CRH Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotr ....Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotrophin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely a rise in CRH occurs earlier in the pregnancy and more rapidly, while in women who deliver late the rise occurs more slowly. This work has given rise to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this research project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done in two ways: (1) by examining the DNA sequences involved in controlling expression of the CRH gene and (2) by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and abnormal birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be invented.Read moreRead less
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to r ....Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to rapidly, at high resolution, elucidate how mechanotransductive cues determine the fate choice of mesenchymal stem cells, and furthermore, how to manipulate them with smart biomaterial design to achieve desired outcomes for tissue engineering. Read moreRead less
Special Research Initiatives - Grant ID: SR1101002
Funder
Australian Research Council
Funding Amount
$21,000,000.00
Summary
Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and ....Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and the ability to control and influence this process. Stem Cells Australia will deliver new methods for stem cell propagation and manipulation, new translational technologies for therapeutic applications, and will prepare Australia’s future stem cell scientific leaders.Read moreRead less
Developing the basis for an quality control platform for human pluripotent stem cells and their differentiated derivatives. Biophotonic techniques based on spectroscopy have the potential to provide low-cost, automatable measurements for the quality control of stem and differentiated cells produced for use in industry and regenerative medicine. This project is aimed at acquiring the fundamental scientific knowledge base required to bring this about.