Award details

A New Platform for Detailed Analysis of High Value Proteins

Reference	BB/W020270/1
Principal Investigator / Supervisor	Dr Karl Burgess
Co-Investigators / Co-Supervisors	Dr Tessa Moses
Institution	University of Edinburgh
Department	Sch of Biological Sciences
Funding type	Research
Value (£)	526,256
Status	Current
Type	Research Grant
Start date	15/02/2023
End date	14/02/2024
Duration	12 months

Abstract

The Agilent 6560C is a heavily modified and improved version of the existing Agilent 6560A instrument, with the vast majority of improvements aimed at the analysis of intact proteins. The 6560 platform itself is a relatively sensitive quadrupole time of flight (QToF) instrument, and performs all of the typical duties that such an instrument can perform, such as small molecule and peptide analysis. The incorporation of the industry's only true drift tube ion mobility system in a commercially available QToF, along with software enhancements that dramatically improve resolution, mean that it is capable of not only direct calculation of collision cross section values (providing structural information about the species detected) but also an orthogonal, relatively high resolution separation capability that helps to further reduce complexity in the increasingly complex samples that 'omics techniques demand. The 6560C adds to the capabilities of the 6560A with the incorporation of electron capture dissocation (for enhanced fragmentation of large, highly charged species such as proteins, and improved analysis of post translational modifications), collision induced unfolding (for structural analysis of large species such as proteins), and a matrix assisted laser desorption ionisation source (intended for analysis of solid state therapeutic peptide arrays). This provides an extremely complementary offering to our existing instruments (the aforementioned 6560A, which is dedicated to metabolomics workflows, a Quantiva triple quadrupole instrument for small molecule targeted analysis, a GC-QToF for polar small molecules and analysis of volatiles, and a Q-Exactive for conventional shotgun proteomics).

Summary

We request an Agilent 6560C ion mobility mass spectrometer to accelerate our engineering biology platform. Industry globally is moving over to the use of bio-based and renewable sources for chemicals, such as plastics, detergents, dyes and medicines. Engineering biology is the term given to modifications of cells that can be our 'factories of the future'. It allows researchers to select or modify the ordinary chemical processes that the cells perform and provide them with new ones. In the case of mammalian cells such as the archetypical Chinese Hamster Ovary cells, synthetic biologists can produce extremely valuable protein medicines such as anti-cancer agents, vaccines and treatments for rare diseases. While our expert teams at UoE now have powerful automated systems for modifying mammalian cells, we struggle to test them to see how well they work and how good (and safe) the products are. Currently assessment of product quality is performed by simply measuring the yield of the products, and does not fully determine the structures or the modifications common to these proteins that can be responsible for safety and efficacy. Full product quality assessment must be done by multiple complex structural and chemical methods housed in multiple facilities. This means that we cannot optimise the engineering biology platform as well as we should be able to within the rapid turnaround times required by industry and modern academic research. The Agilent 6560C is an instrument that can characterise the product quality of high value proteins. With this system, we can 'close the loop' of engineering biology, and by using rapid testing, refine our engineered cells to make safer and better products. By adding this capability to EdinOmics and the portfolio of support facilities at the University of Edinburgh, we will provide world leading researchers into new medicines with the technology to take an idea for a new drug through early stage genetic engineering (via the Edinburgh Genome Foundry), through early stage production of a new medicine (via the Edinburgh Protein Production Facility) to testing of that medicine for quality (via this new instrument). Production of such highly polished early stage medicines can accelerate their uptake for clinical trials and hence medical use.

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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