The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date
Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family protei ....Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family proteins in spermatogenesis. The outcomes will define the different roles of highly similar proteins from the same family in differentiation of a single cell lineage. This is important in generating functional tissues using in vitro laboratory approaches or understanding how normal development and developmental disorders arise.Read moreRead less
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
Understanding the potency and role of individual stem cells in the skin using Rainbow technology. To renew itself, the skin and its components rely on the activity of stem cells. This project will define more precisely the role of each individual stem cell by labelling them with a unique colour and following its fate. This project has the potential to change our current view on how the skin maintains and repairs itself.
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insig ....Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insights into the molecular regulation of how cells orchestrate and integrate cell death pathways. This should provide significant benefits, such as providing the knowledge base needed to improve our abilities to manipulate cell death both in basic research and commercial applications of cell death.Read moreRead less
Targeting mitochondria with mitocans to treat cancer: mechanistic aspects. Mitochondria are the power-house of the cell and also the reservoir of proteins causing the demise of cancer cells, therefore suppressing tumour progression. This project proposes a novel way to modify certain compounds, increasing their level in mitochondria in order to maximise their anti-cancer effect.