Liquid Chromatography-Mass Spectrometry for the Analysis of Biological Small Molecules in Metabolomic, Nutritional, and Toxicological Studies.

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This proposal requests support for a piece of equipment called a liquid chromatography - mass spectrometer (LC-MS). This equipment allows researchers to measure the mass of particles, and to find the basic chemicals that make up a biological sample such as blood, tissue or food. The LC-MS requested in this proposal will support research from multiple scientific disciplines, and on several distinct projects of great importance to the health of the population:Example Project 1: Given that 340 million people worldwide suffer from type 2 diabetes, finding new treatments is essential. White fat tissue stores energy as fat and releases signals into the blood which communicate with other organs, regulating whole-body metabolism. However, not all fat cells are identical. A second fat cell population, brown fat cells, regulate body temperature by "burning" stored fats, producing heat. A third fat cell population, beige fat, can switch from behaving like white fat cells (storing fat) to functioning like brown fat cells (burning fat), a process called "browning". In humans, beige fat may form the majority of this heat-producing tissue, and is also found within white fat tissue. Beige fat has anti-diabetic properties which may, in part, occur through release of signals into the blood which alter metabolism in tissues such as liver, muscle and white fat.This research will use the requested LC-MS to determine whether browning of white fat tissue results in metabolite signal secretion, and to identify these signals. The capacity of metabolite signals to induce browning in neighbouring white fat tissue and to signal, via the blood, to other organs to regulate whole-body metabolism, will be investigated. This research may identify beige cell-specific metabolite signals, with anti-obesity properties, and provide new anti-diabetic therapies.Example Project 2: Food constituents can have profound effects on wide ranging aspects of health including gut function, control of blood glucose and our ability to think. Wheat and other food crops contain naturally occurring compounds, called phenols, which may have anti-oxidant effects that reduce cellular damage to DNA known to be important in cancer and ageing. They may also improve gut function. This project will use the LC-MS to measure the antioxidant phenols, and micronutrients in models of gut function to understand how readily these antioxidant phenols are absorbed from food, determine ways of improving their uptake, and to measure the absorption of other micronutrients across the gut in the presence of the phenols to determine how they affect gut nutrient uptake. Example Project 3: Food contaminants and toxins are a major risk to human health and have particular impact on vulnerable communities in low income countries. A particular group of toxins know as mycotoxins, derived from fungus, can contaminate food crops such as maize and wheat and have been linked to reduced child growth and development, and the development of cancer. This project will use the requested LC-MS to measure levels of the toxins and markers of exposure to the toxins in human populations from Africa to understand distribution patterns of contamination in different crops, storage conditions and geographic locations and to assess the effectiveness of interventions to reduce mycotoxin risk in Africa. Therefore contributing to the safety and security of the global food industry.Example Project 4: Exposure to environmental pollution in the form of particulates from traffic in the air can alter the way in which blood clots and contribute to deep vein thrombosis. This project will use the requested LC-MS to measure markers of exposure to the particle pollutants in blood samples of the population to understand the effects of pollution on cardiovascular health.