Mass spectrometry underpinning synthetic biology, industrial biotechnology and world class bioscience

The application of biological mass spectrometry, in particular in the field of proteomics has revolutionised the ability of study a wide range of biological systems and answer important questions. Biological mass spectrometry is of central importance and currently underpins a diverse range of studies, across a wide range of biological systems. Within the Department of Chemical and Biological Engineering (CBE) we have significant expertise in the application of mass spectrometry approaches and have used this technology to answer important questions including; 1) how bacteria defend themselves from viruses 2) protein organisation in photosynthesis 3) how can we optimise cells to produce important products.

The Q Exactive Plus instrument is new to market (released Sept 2013) and provides the opportunity for the University of Sheffield and it's research partners to make a step-change in the scope of research activities. The instruments unique features will accelerate our academic and industrial research.

Underpinning our strong industry connections, the University of Sheffield has recently established an Advanced Biomanufacturing Centre (ABC). Arising from the Dept of Chemical and Biological Engineering, the aim is to develop interdisciplinary industrially-relevant research for biomanufacturing and bioprocessing within the UK bioindustry. The proposed instrument will be a critical asset; underpinning research associated with biomanufacturing and bioprocess development and will underpin an extensive portfolio of current BBSRC funded research, demonstrating the huge value of the equipment.

Within the emerging areas of synthetic biology and industrial biotechnology, the development and application of high-throughput, quantitative biological mass spectrometry (MS) approaches will underpin established and potential research in these critically important areas. However, the demand for increased throughput, unmatched sensitivity and quantitative applications of biological MS will require new instrumentation that is not currently available at the University of Sheffield.

The Q Exactive Plus instrument is new to market (released Sept 2013) and provides the opportunity for the University of Sheffield and it's research partners to make a step-change in the scope of research activities. The instruments unique features, allow for targeted quantification of peptides, small molecules and nucleic acids and delivers high throughput, targeted quantitation combined with high-resolution accurate-mass data, that will accelerate our academic and industrial research. Fast polarity switching, parallel reaction monitoring (PRM), high-resolution accurate-mass selected ion monitoring (HR/AM-SIM) are just some of the techniques we will employ to our systems biology research with enhanced sensitivity and selectivity.

The proposed instrument will underpin an extensive portfolio of current BBSRC funded research, demonstrating the huge value of the equipment. Moreover, this will facilitate new and novel research opportunities and new impacts within industrial biotechnology, synthetic biology, and world leading bioscience. Furthermore, the proposed instrument will be a critical asset in the recently established Advanced Biomanufacturing Centre; underpinning research associated with biomanufacturing and bioprocess development. This will enable a step change in the biological MS workflows and analytical capability for users (academic and industrial), beyond current through-put and quantitation limitations, as a complement to existing assets.

The aim of this proposal is to purchase a new mass spectrometer. The primary impact of the proposal will result from the research that we propose to carry out in the immediate future. Furthermore, it is expected that further impact will result from new and novel research opportunities and new impacts within industrial biotechnology, synthetic biology, and world leading bioscience areas.
The projects that focus on the areas of Industrial Biotechnology/ Synthetic Biology are of direct relevance to UK bioindustry and a wide range of the proposed research will be of fundamental importance to pharmaceutical / biopharmaceutical industries, with more immediate impact than those addressing more fundamental science. The proposed equipment will support projects aimed at developing biological medicines including protein therapeutics produced by E. coli and mammalian cells in culture. It will also support projects related to the identification and characterisation of oligonucleotide therapeutics. As part of the proposed research, methods will be generated that can be implemented immediately to reduce time and costs spent in the creation of biomanufacturing systems - this represents a clear economic benefit and increased capability and competitiveness for UK bioindustry.

In addition, the equipment will underpin a number of projects relating to more fundamental science that are likely to have more longer term impact, however will benefit those pharmaceutical companies including those developing novel antifungal agents and Health professionals preventing and managing C. albicans infection. In order to generate suitable therapeutics for treatment of disorders involving mRNA export it will be essential to understand the specific roles of target proteins in this process. This study will greatly expand our knowledge in this area and identify new potential targets for future therapeutic interventions involving mRNA export diseases. The understanding of photosynthesis is of fundamental importance as the basis of life on Earth, but also has the potential to impact upon the search for a sustainable energy future.

The new mass spectrometer will facilitate training in cutting edge mass spectrometry and inter-disciplinary science. As part of the Advanced Biomanufacturing Centre at the University of Sheffield, the aim is to develop interdisciplinary industrially-relevant research for biomanufacturing and bioprocessing within the UK bioindustry. The proposed instrument will be a critical asset underpinning research associated with biomanufacturing and bioprocess development. We will provide highly skilled PhD students and PDRAs capable of working in this inter-disciplinary environment throughout the UK. The new instrument will attract new users from other Universities and Industry who will benefit from the excellent training environment.