Osteosarcoma is the most common tumour of bone. Recent success in targeting immune checkpoint blockers such as Programmed death-1 (PD-1) in genomically complex tumours suggests that osteosarcomas may be amenable to such strategies. We will characterise the role of the PD-1 pathway in osteosarcoma development and growth. Using preclinical mouse models we will investigate the biology of the PD-1 pathway and study its potential as a therapeutic target in advanced and resectable osteosarcoma.
Combating Bacterial ‘superbugs‘ By Innovative Dosing Strategies That Combine Available Antibiotics To Prevent Resistance
Funder
National Health and Medical Research Council
Funding Amount
$547,694.00
Summary
As resistant bacterial ‘superbugs’ are among the 3 most serious threats to global health and as new antibiotics are lacking, innovative strategies to prevent bacterial resistance are urgently needed. This proposal will yield molecular insights on optimal combinations of current beta-lactam antibiotics to maximise bacterial killing without resistance. This project will provide guidance to physicians on how to optimally combine available beta-lactam antibiotics to prevent bacterial resistance.
The many moral rationalisms. This project addresses the foundations of morality. It contributes to our self-understanding by generating new insights into the objectivity of morality and into the role of reason and emotion in moral judgment.
Agency, Rationality, and Emotion. This project addresses the puzzling and multiple connections between emotion and reason. Emotion, long viewed as an impediment to rationality, actually helps us reason well. Our image of good public deliberation as unemotional needs to be challenged and our understanding of the place of reason and emotion in human life needs to be revised. The project engages and contributes to new international research on emotion and rationality thereby contributing to Austral ....Agency, Rationality, and Emotion. This project addresses the puzzling and multiple connections between emotion and reason. Emotion, long viewed as an impediment to rationality, actually helps us reason well. Our image of good public deliberation as unemotional needs to be challenged and our understanding of the place of reason and emotion in human life needs to be revised. The project engages and contributes to new international research on emotion and rationality thereby contributing to Australia's international reputation for excellence in philosophy.
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Pathologies of moral cognition. The saying "Nice guys finish last" captures the thought that moral cognition makes us vulnerable to exploitation. This project aims to examine this hypothesis by investigating three aspects of moral cognition that might lead us to form false beliefs or render us vulnerable to manipulation by others: our beliefs about punishment; our tendency to identify with groups; and our willingness to trust others. The project is designed to involve empirical investigation of ....Pathologies of moral cognition. The saying "Nice guys finish last" captures the thought that moral cognition makes us vulnerable to exploitation. This project aims to examine this hypothesis by investigating three aspects of moral cognition that might lead us to form false beliefs or render us vulnerable to manipulation by others: our beliefs about punishment; our tendency to identify with groups; and our willingness to trust others. The project is designed to involve empirical investigation of the circumstances in which moral behaviour can have harmful side-effects; it also entails theoretical analysis intended to improve our ability to construct robust theories of cooperative and punitive behaviour.Read moreRead less
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Self-control and pathologies of agency. This project will develop a philosophically and scientifically sophisticated account of the nature of self-control. This account will provide tools for allocating responsibility for failures of self-control and will contribute to the development of means for enhancing it, thereby aiding in addressing major social problems.
Challenges to moral responsibility. Agents deserve various kinds of benefits and burdens (such as punishment) only if they are morally responsible for their actions. This project aims to assess several sorts of alleged threats to our moral responsibility, and thereby to better the social allocation of goods to individuals.
Conscience and conscientious objection in health care. Medical professionals sometimes decline to provide particular forms of safe, beneficial and legal health care, on the grounds that provision would go against their consciences. Bioethicists and policy makers have failed to identify legitimate limits to the scope of appeals to conscientious objection in health care. This is in large part because the underlying concept ''conscience" is unclear. This project aims to advance bioethical debate by ....Conscience and conscientious objection in health care. Medical professionals sometimes decline to provide particular forms of safe, beneficial and legal health care, on the grounds that provision would go against their consciences. Bioethicists and policy makers have failed to identify legitimate limits to the scope of appeals to conscientious objection in health care. This is in large part because the underlying concept ''conscience" is unclear. This project aims to advance bioethical debate by producing a philosophically and psychologically informed analysis of conscience, and by applying this to discussions about the legitimate limits to conscientious objection in health care. It is expected to result in academic and non-academic publications and enable improvements to Australian health care policy.Read moreRead less
Moral conservatism, human enhancement and the 'Affective Revolution' in moral psychology. Debates between moral conservatives and liberals, about whether enhancing human mental and physical abilities above normal limits is ethically acceptable, have been intractable. Recent developments in moral psychology can be used to transform understandings of these debates and enable us to develop just policies to regulate enhancement technologies.