Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understandi ....Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understanding of histone deacetylases and protein deacetylation in immune cell responses which can be harnessed to manipulate cell functions for basic science and biotechnology uses.Read moreRead less
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less
Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes in ....Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes include new insights into how immune cells and tissues respond according to the posing threat. Project benefits include understanding how to manipulate danger responses for future basic research and commercial applications, and fundamental understanding of how animals flourish in a dangerous world.Read moreRead less
A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project wi ....A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project will yield exciting new knowledge of mechanisms of inflammation and anti-microbial responses, and new paradigms for inflammasome action. Expected outcomes and benefits include high-impact publications, international collaboration, world-class training for young scientists, and new knowledge for future commercialisation.Read moreRead less
How filopodia connect macrophages to the outside world. Fundamental to life is the ability of cells to sense their surroundings and respond accordingly. This project aims to generate a biological understanding of how certain immune cells carry out such processes, thus enabling them to combat infections.
The role of a novel protein, interferon epsilon, in reproductive tract immunity. This project aims to develop a world-first description of a new protein that has a protective role against female reproductive tract infections. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in diseases such as Chlamydia and Herpes Simplex Virus.