Establishment of mass spectrometry based proteomic capabilities at Queen's University Belfast

The ASSET Technology Centre in the School of Biological Sciences (SBS) and Institute for Global Food Security (IGFS) at Queen's University Belfast (QUB) focuses on addressing bioscience, food-safety and animal-health challenges. This proposal seeks to establish, at QUB, cutting edge capability, within ASSET, for proteome analysis. The proteome is a term used to describe the entire set of proteins that are produced by a given cell, tissue or organism at any given time. Analysing the proteome allows us to gain a better understanding about how organisms and cells actually function and respond to different environments or challenges.

We measure the proteome using techniques called mass spectrometry and liquid chromatography (LC-MS). We wish to purchase an LC-MS system, a Bruker timsTOF HT. This system is superior to other instruments; it is faster, more sensitive and more versatile. It also has advanced ion mobility, which means that it can separate almost identical peptides (small sections of proteins) based on how they move through the instrument. This is particularly powerful for work on post-translational modifications (understanding molecules that direct proteins to complete different tasks).

There is currently no central capability to do this at QUB. The requested equipment would be transformative at QUB as the 'final piece in the jigsaw' providing a whole systems biology pipeline for more than 70 research groups within IGFS, SBS and to an even greater number across the University. In the short term, this instrumentation will support a number fundamental science research projects worth millions of pounds. Over the medium to longer term the equipment will provide opportunities for the development of novel research themes in the delivery of new approaches and solutions for the SBS & IGFS priorities in bioscience, food integrity, farms, animal health and crop integrity addressing the future and nutritional challenges of the 21st Century. The exemplar projects outlined within this proposal demonstrate the multidisciplinary purpose & use of the equipment ranging from bacterium to human, biochemical engineering to terrestrial ecology, computational biologist to clinical biologists, and a swathe of organisms and disciplines in between. Clearly this system will be used across a wide range of applications and will build capacity to interact with industrial partners from a range of industries, including food processing and safety, diagnostics and agriculture sectors across Northern Ireland and the UK. The requested equipment will provide an important contribution to research training within the research community. More advanced training will occur in conjunction with our partners in both university and industry, with on-site training programmes where scientists will be hosted within ASSET and trained in the background and practical applications of the instrumentation, upskilling the national and international workforce in a key technology.
This instrument will be transformative for confident proteome analyses of biological samples within the scientific community at QUB. This will enable projects across QUB, its wider partners and collaborators that would previously not be possible. Enhancing the Northern Ireland economy and aiding in provincial levelling up.

We are requesting funding for a timsTOF HT LC-MS. The instrument will be housed in the world renowned ASSET Technology Centre in the School of Biological Sciences bringing central proteomic capabilities to Queen's University Belfast. The timsTOF HT has a dual- trapped ion mobility spectrometry (TIMS) analyser allowing parallel accumulation, serial fragmentation PASEF, dia-PASEF and prm-PASEF to be performed. This innovation results in nearly 100% duty cycle leading to increased sensitivity, with robust identification and quantitation of proteins in the low ng range. The system is quicker than equivalent instruments, accumulating ions in TIMS tunnel 1, while ions in TIMS tunnel 2 are released sequentially giving > 150 Hz, meaning it can gain sequence information on more than 150 peptides per second. The TIMS confers an advantage for separation of essentially isobaric peptides based on their mobility in the drift tunnel. This is particularly powerful for PTM work especially positional isomers, in acetylations on lysine for epigenetic analysis and phosphorylation's associated with signalling.
The instrument will support a number of UKRI funded projects in addition to supporting research themes aligned with BBSRC high-level objectives- Advancing the Frontiers of Bioscience Discovery and Tackling Strategic Challenges.
The timTOF HF meets all the requirements to support the myriad of projects encompassed by SBS & IGFS, QUB and the wider Northern Ireland economy. It is superior to the other instruments currently available, it is faster, more sensitive and more versatile, with unique features and benefits. It will fit seamlessly into the ASSET centre bringing a new dimension of research capabilities. Commissioning and workflow setup will be expedited by the application of established workflows that Dr Ben Collins has been instrumental in developing. Ensuring rapid scale-up of new users and projects which previously could just not have been supported at QUB.