Award details

MUSERMET: MultiUSER equipment for small molecule identification in untargeted METabolomics

Reference	BB/S019030/1
Principal Investigator / Supervisor	Professor Douglas Kell
Co-Investigators / Co-Supervisors	Professor Toby Bruce, Professor Mark Caddick, Dr David Dickens, Professor Patrick Eyers, Professor Royston Goodacre, Professor Andrew Jones, Professor Luning Liu, Professor Steve Paterson, Professor Soraya Shirazi-Beechey
Institution	University of Liverpool
Department	Institute of Integrative Biology
Funding type	Research
Value (£)	479,971
Status	Completed
Type	Research Grant
Start date	01/07/2019
End date	30/06/2020
Duration	12 months

Abstract

Many of the projects in the newly formed Liverpool Centre for Metabolomics Research involve a requirement for the sophisticated, detailed, and RAPID analysis of biological samples to identify and measure the small many hundreds or thousands of molecules (metabolites) that they contain. This is typically done using liquid chromatography followed by high-resolution mass spectrometry, including the masses of any fragments that may be produced. Classically, a major bottleneck has been the IDENTIFICATION of the metabolites represented by what may otherwise be highly reproducible retention times and MS^n mass spectra. An instrument called the Orbitrap ID-X tribrid, together with an integrated suite of software (to which we shall add), offers a real chance of proving the necessary spectra and solving this 'spectrum-to-structure' problem. It may be applied to multiple problems within the BBSRC remit, and we illustrate several. The aim of this proposal is to secure such an instrument for an extensive User Community in Liverpool and elsewhere. The instrument, while based on established Orbitrap technology, is both novel and unique, and no such instrument is available within the UK.

Summary

Many of the projects in the newly formed Liverpool Centre for Metabolomics Research involve a requirement for the sophisticated, detailed, and RAPID analysis of biological samples to identify and measure the many hundreds or thousands of small molecules (metabolites) that they contain. This is done by separating them in a flowing stream (liquid chromatography) followed by their estimation on the basis of their masses and the masses of any fragments that may be produced therefrom (as these form a unique 'signature'). Classically, a major bottleneck has been the IDENTIFICATION of the metabolites represented by what may otherwise be highly reproducible times of the appearance of these mass spectral peaks or signatures. An instrument called the Orbitrap ID-X tribrid, together with an integrated suite of software (to which we shall add), offers a real chance of solving this 'spectrum-to-structure' problem. It may be applied to the solution of multiple problems within the BBSRC remit, and we illustrate several. The aim of this proposal is to secure such an instrument for an extensive User Community in Liverpool and elsewhere. The instrument, while based on established Orbitrap technology, is both novel and unique, and no such instrument is currently available within the UK. This would be a 'first', and we have accordingly secured a substantial contribution from the applicant Universities.

Impact Summary

WHO WILL BENEFIT: Companies will benefit in a number of ways, by (i) gaining access to knowledge of methods used for the rapid analysis of biological systems using state-of-the-art XC-MS instrumentation and its attendant analytics, and e.g. (ii) knowledge of how to improve the production of various compounds, whether they are substrates, intermediary metabolites, nutraceuticals, drugs, or bioactives in any kind of products. So far as industrial biotechnology more generally is concerned, companies will benefit from knowledge of a novel strategy for rapid cell analysis. HOW WILL THEY BENEFIT: As is our practice, all pertinent data are made available via the Web, and OA publishing has long been our norm. We also hold frequent workshops to assist dissemination of research results. We have pioneered in the Altmetrics field for digital dissemination - indeed a recent Nature article (Kwok R: Altmetrics make their mark. Nature 2013; 500:491-492) highlighted the fact that the PI's paper Hull D, Pettifer SR, Kell DB: Defrosting the digital library: bibliographic tools for the next generation web. PLoS Comput Biol 2008; 4:e1000204 was the most accessed in ANY PLoS journal, with over 53,000 accesses! (it is past 108,000 now) - the PI's paper Kell DB: Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genom 2009; 2:2 has over 98,000 accesses, increasing at ~50 per day).We shall work closely with University KT staff and industrial IP offices to secure intellectual property rights for any useful inventions that we discover. Having secured IP, future development work can take place, and several routes to commercialisation can be explored. For example, all pharmaceutical companies have their own relevant groups, with whom we are in contact. Finally, having secured IP, we shall, of course, seek actively to communicate our scientific findings to the wider researchcommunity through scientific meetings, scholarly publications and press releases. THE WIDER COMMUNITY: DBK (@dbkell) and RG (@RoyGoodacre) are well known and regular tweeters (the latter also runs the @metabolomics twitter feed), and social media will provide a novel and useful means of disseminating our findings. Both are regular attenees at thee MetaboMeeting and International Metabolomics Society's conferences. COMMUNICATIONS: We will communicate with relevant industrial partners both directly and via the meetings of relevant learned societies (we are members of several). In year three of the Project, we will organise a half-day meeting to explain our research to interested industrial scientists. However, we will also provide a video link to facilitate the participation of those who are unable to travel to Liverpool.

Committee	Not funded via Committee
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Advanced Life Sciences Research Technology Initiative (ALERT) [2013-2014]
Funding Scheme	X – not Funded via a specific Funding Scheme

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