Unravelling challenges to lifelong health by next generation Mass Spectrometry

Lead Research Organisation: University of Edinburgh
Department Name: Centre for Cardiovascular Science

Abstract

Hormones are crucial signalling messengers in humans and other organisms, including mammals, birds and fish. They travel in the blood to organs (e.g., liver, fat, ovaries, testes, brain) to control vital day-to-day processes such as reproduction and feeding, and also enable swift responses in response to stress e.g., fear, starvation, cold.

Within organs, there are suites of cell types, all with different functions. Each cell has mechanisms to fine tune the amount of hormone acting e.g., pumps drawing in or removing hormones, proteins acting as storage tanks to hold reserve hormones or enzymes changing hormones between active and inactive states.

Bio-scientists must measure hormones in these tiny pools to fully understand interlinked pathways forming the basis of health. With technology improving, even measurement in individual cells is coming into reach. Here we invest in a next-generation "liquid chromatograph triple quadrupole mass spectrometer" allowing us to measure hormones (and other small molecules) at previously unreachable levels of sensitivity and precision and indeed outperforming our existing instrument ten fold. Crucially, with greater sensitivity, this new instrument will allow measurement of hormones in smaller sized samples e.g., neonatal hair, exhaled breath and in small animals.

Our team comprises research technical professionals (RTPs) and basic and clinical academic researchers working collaboratively. Our RTPs are experts in creating new, reliable approaches to maximally benefit from technology innovations and will develop ways to measure hormones in substantially lower levels than before. This will allow us to find hormones previously too low to measure e.g., aldosterone that controls blood pressure, sex hormones in ageing. Our RTPs will ensure high quality methods and robust dataflows to minimise human error, reporting to Good Clinical Practice, a high regulatory standard.

Through team science, our basic scientists and clinicians will drive forward novel projects studying, e.g., neonates to understand stress and nutrition in pregnancy; animal models of metabolic health, from mice lacking proteins to pump or store reserve hormones to non-invasive free-living measures through hair and saliva sampling in large animal models; reproduction of managed and wild animals (e.g., birds, fish, horses) linking environmental stimuli to reproduction (nesting behaviour, water temperature); and mammalian models to unpick interactions between heat-generating fat (brown), body weight and environmental temperature.

Thus with this new sensitive instrument we will implement new methodologies requiring extremely sensitive analytical technology to enable hormone analysis and open doors to previous unattainable scientific insights. In due course we will support wider bioscience in Edinburgh (e.g., neuroscience) and beyond (metabolic health), including working with industry. We will train and mentor our RTPs in advanced skills, and support and educate the next generation of bio-scientists. We have designed a robust programme to install and maintain the new system and built a business plan to ensure effective management moving forward within a specialist technology hub.

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