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.
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.
Microenvironments which support extramedullary hematopoiesis. Tissue regeneration is a breakthrough technology absolutely dependent on knowledge of the stem cells and stromal cells which support differentiation and tissue development. This project investigates the stromal cell types in spleen which can regenerate blood-forming cells in an ectopic tissue site or artificial matrix.
Role of senataxin protein in meiotic recombination and sex chromosome inactivation. Senataxin is a protein defective in the human genetic disorder ataxia oculomotor apraxia type 2. This project is designed to carry out mechanistic studies on the protein to establish its normal role in the cell.
Functional Dyspepsia: Characterisation Of The Immunopathology And Testing A Novel Therapeutic Strategy.
Funder
National Health and Medical Research Council
Funding Amount
$739,604.00
Summary
Dyspepsia, unexplained stomach discomfort and pain, is a common and costly problem; few effective treatments exist and the causes are unknown. We have found that the numbers of a type of immune cell, the eosinophil, are increased in the top of the small bowel in patients with dyspepsia. This study will explore the mechanisms that lead to increased eosinophils and then test the effectiveness of a treatment to suppress this overactive immune response which could rapidly change clinical practice.
Pyroptotic macrophages posthumously sculpt immune responses. The life of an organism relies on the timely birth and death of its cells. Importantly, it is crucial for cells to die not only at the right time, but also in an appropriate manner. This proposal investigates a cell death pathway that triggers potent immune responses. This proposal seeks to reveal precisely how cell death sculpts immune responses. Expected outcomes include new insights into how immune cells die, and how they instruct i ....Pyroptotic macrophages posthumously sculpt immune responses. The life of an organism relies on the timely birth and death of its cells. Importantly, it is crucial for cells to die not only at the right time, but also in an appropriate manner. This proposal investigates a cell death pathway that triggers potent immune responses. This proposal seeks to reveal precisely how cell death sculpts immune responses. Expected outcomes include new insights into how immune cells die, and how they instruct immune responses from beyond the grave. Project benefits include a fundamental understanding of how cell death signalling sculpts tissue immune responses, and knowledge of how to manipulate cell death responses for future basic research and commercial applications beyond this project.Read moreRead less
Tolerising Antigen-specific Immunotherapy For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,395,549.00
Summary
We have developed a new immunotherapy to treat the underlying causes of type 1 diabetes (T1D) while leaving the rest of the immune system intact. To use this in patients, we need better tests to know when immune therapy is working. We will develop new methods to design the therapy and tools to track the relevant immune cells in T1D that work in variable patient groups. The knowledge gained will speed the pace of development and increase the chance of success of immunotherapy in T1D.
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.
Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and w ....Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and whether neurogenesis may be induced by inflammation in the adult. Using transcriptomics we will also determine how the neurogenic environment changes with age/inflammation. This project is an important step in proving that the brain's potential to generate new neurons extends beyond infancy.Read moreRead less
Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and ....Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and immune cell death via the non-canonical inflammasome. We do not currently understand how some immune pathways are turned on or off. This project will yield fundamental insight into mechanisms of mammalian inflammasome, inflammation and anti-microbial responses.Read moreRead less