Understanding gender differences in pain: Cellular therapies for animal pain. Understanding gender differences in pain: Cellular therapies for animal pain. This project aims to relieve chronic pain in animals and lay the foundations for future human therapies, using molecular assays, cell technologies and immune/hormonal pain generators. Chronic pain affects females more than males. Establishing the fundamental mechanism in pain, the role of immune signalling and molecular mediators will enable ....Understanding gender differences in pain: Cellular therapies for animal pain. Understanding gender differences in pain: Cellular therapies for animal pain. This project aims to relieve chronic pain in animals and lay the foundations for future human therapies, using molecular assays, cell technologies and immune/hormonal pain generators. Chronic pain affects females more than males. Establishing the fundamental mechanism in pain, the role of immune signalling and molecular mediators will enable true pain-modifying treatments that address pivotal triggers in both genders. This project will then use specially selected stem cells separately targeting arthritic male and female pain and demonstrate novel veterinary chronic pain treatments. Expected outcomes are more effective gender-targeted treatments of pain and the realisation of economic value of molecular assays and cell technologies.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less