A high sensitivity elemental mass spectrometry facility to support metallo-biology research on the Norwich Research Park

Metals are essential for all forms of life, playing central roles in many of the reactions on which life depends, including, for example, respiration and photosynthesis. However, the properties that make metals essential also mean that they are potentially extremely toxic, and so living organisms have evolved often highly sophisticated systems through which they manage the uptake, utilisation and detoxification of metals. In some cases, such as iron, the metal can be difficult to acquire in sufficient quantities. Although iron is abundant in the earth's crust, it is highly insoluble and this severely limits its availability to living organisms, including humans, and, as a result, iron deficiency is the most widespread global nutritional deficiency. This application brings together a group of internationally leading researchers at the University of East Anglia, John Innes Centre and Quadram Institute Bioscience. It is focussed on understanding how metals function, how they are handled by cells/organisms and how this knowledge can be exploited for our benefit, for example: in developing news ways to interfere with essential metal-dependent pathways in disease-causing bacteria; in generating improved food crops with increased metal nutritional content; and in developing biotechnological processes that are based on natural metalloenzyme systems. Progress in all these projects is absolutely dependent on being able to accurately measure metal concentrations. For example, in developing improved food crops, researchers must be able to measure the nutritional metal (iron and zinc) contents of the crops but also concentrations of toxic metals such as cadmium to ensure that increased metal levels are confined only to those of nutritional value. Thus, to facilitate these projects and to allow them to develop in new ways, the application seeks support for the purchase of a new instrument, a type of mass spectrometer, which enables researchers to measure with great accuracy and sensitivity the amounts of different elements, including metals, but also sulfur and phosphorus, in a range of biological samples.

Inductively coupled plasma triple quadrupole mass spectrometry (ICP-QQQ-MS) provides state of the art, high sensitivity detection and quantification of a range of elements, particularly metals, sulfur and phosphorus. Triple quadrupole instruments overcome interference problems associated with earlier single quadrupole instruments, where the ability to operate in MS/MS mode enables interference ions of the same mass as the target analyte to be distinguished. Thus elements such as iron, sulfur and phosphorus, which are very difficult to detect and quantify using a single quadrupole instrument due to interference ions (eg. ArO interferes with Fe), can be readily detected at parts per billion (ppb) to parts per trillion (ppt) levels. This technology will facilitate on-going projects at UEA, John Innes Centre and the Quadram Institute Bioscience, which rely on the ability to detect metals (and sulfur) accurately and with high sensitivity. The research programme focusses on three themes: Metal and sulfur biochemistry underpinning life (theme 1), which addresses how (mainly) iron and sulfur biochemistry is exploited in living systems to carry out a wide range of functions in e.g. sensing, energy metabolism and metal metabolism; Human and animal nutrition (theme 2), in which efforts are focussed on understanding metal ion metabolism in crop plants and how the essential metallo-nutrient content of these can be increased using natural breeding approaches; and Climate gases and bioenergy (theme 3), which focusses on the roles of iron containing monooxygenase enzymes that play key roles in the utilisation of methane and isoprene, two atmostpheric gases produced naturally on a massive scale. The availability of ICP-QQQ-MS on site will open up opportunities for these projects to develop in ways that are not currently possible, for example through the coupling of MS with front end ion chromatography to enable analysis of complex biological samples.

This application for an inductively coupled plasma triple quadrupole mass spectrometer (ICP-QQQ-MS) instrument will support a range of projects at the University of East Anglia, John Innes Centre and Quadram Institute Bioscience that relate to themes in Metal and sulfur biochemistry underpinning life (theme 1), Human and animal nutrition (theme 2), and Climate gases and bioenergy (theme 3). These projects will have diverse and far reaching impacts within the UK and internationally.
Outside of academia, there are several groups of potential beneficiaries, including:
- policy makers and commercial stakeholders, who are likely to be interested in the anticipated advances in understanding how microorganisms, including pathogens, sense nitric oxide and other oxidative/nitrosative stresses via iron-sulfur cluster regulatory proteins. In the longer term, the detailed knowledge about NsrR/WhiD and other Rrf2/Wbl family members that function as regulators could lead to the development of novel antimicrobial compounds that interfere with the stress-sensing mechanisms. The research projects on iron, zinc and magnesium in crops are linked to several soil quality and fertiliser SMEs in the region, leveraged though the on-going relationships we have with these organisations and have significant potential for both policy and commercial impact. The project on phytates, in connection with an industrial partner (AB Vista), is likely to lead to impact in the area of animal nutrition technology. The project on the development of garlic polysulfides as a nematicide in potato crop protection involves two SMEs (ECOspray Ltd and TargetSet Ltd);
- the biotechnology and pharmaceutical sectors and public sector laboratories, from the point of view of benefiting from future employment of the state-of-the-art training in ICP-MS element detection provided to PDRAs and PhD students and undergraduates working within the applicants' research groups;
- schools and the general public, who benefit from engagement activities running parallel with the research effort, which seek to inspire the next generation of science undergraduates and scientists and to better inform the general public of key scientific concepts and issues over which society has an influence. The vital role that metal ions play in maintaining health (of e.g. humans, molluscs, plants, yeast and bacteria) is really not well appreciated by the general public. Proteins that bind metal cofactors account for at least 30% of all proteins, and so this is a very important subgroup of proteins. The applicants have a lot of experience of delivering engaging presentations to School and general public audiences.