Next Generation Techniques for Analysis of Biomolecular Systems

The discovery of the structure of DNA more than 50 years ago marked the birth of molecular biology and demonstrated the need for interdisciplinary research in answering its fundamental questions. Since then a myriad of different biological molecules have been discovered which perform a diverse range of functions in living organisms. The detailed structure of each molecule, as opposed to its purely chemical composition, is crucial in determining the precise role it plays. More recently the importance of the dynamic properties of these molecules in response to external stimuli has been recognised. Many of these transient processes are electronic in nature and therefore occur on femtosecond (million billionth of a second) timescales or less, for example the harvesting of light in photosynthesis and radiation damage and repair in DNA. The ongoing development of new laboratory- and facility-based light sources capable of generating ultrashort, intense light pulses over a range of wavelengths, will provide opportunities to generate unprecendented information on the structure of biological molecules and to unravel their ultrafast dynamic behaviour. In this project the latest ultrafast laser, ion storage, and mass spectrometry technologies will be utilised to develop methods for determining the structure and dynamics of peptide molecules. This will be a benchmark for extending the use of these methods to more complicated biomolecular structures which cannot be studied with conventional techniques. Ultimately this will give the candidate the experience necessary to exploit the powerful new light sources which will become available in the next 5-10 years, for the purposes of advancing understanding of molecular structure and dynamics in biological sciences.

This research is likely to generate interest from a number of multi-national companies interested in making improvements to their mass spectrometry instrumentation. Examples of such companies with UK offices are Agilent, Perkin Elmer, Shimadzu and Thermo Fisher Scientific which has a research facility in Cambridge. In the short to medium term, this technology could find a market in advanced research laboratories or facilities such as the EPSRC National Mass Spectrometry Service Centre. More widespread commercial applications would require continuing advances in ultrafast laser technology towards turnkey operation. Such an application could stimulate growth in this market which would benefit companies like Coherent UK Ltd. In the longer term, this technology could be an important tool in the fields of genomics and proteomics which are fundamental for assessments of disease risk, disease occurrence, therapeutic response, and prognosis. If the technology could be developed for DNA sequencing, it would revolutionise DNA analysis due to the orders of magnitude improvements in speed and sensitivity compared with conventional gel electrophoresis. The primary outlet for research output will be through publication in peer reviewed physical chemistry, photobiology, and mass spectrometry journals. If the techniques are as promising as I believe, I expect that they will merit exposure to the extensive audience found in the journals Science and Nature. Towards the end of the project, the facets of the work which have a broader appeal will be promoted in local and national media outlets via the QUB Communications Office. A website, www.ultrafastbiology.com, will be created and maintained to report significant progress and publications resulting from the work. A separate section will also provide a more general overview of the motivations for the research, so that a more general audience can appreciate its impact. The work will also be submitted for presentation at a number of international conferences, e.g. American Society for Mass Spectrometry's Annual Meeting which is regularly attended by around 6000 delegates and has a very strong corporate presence, providing an excellent opportunity for generating commercial interest. The Knowledge Exploitation Unit at QUB manages a range of business activities on behalf of the University including technology licensing, technical services, knowledge transfer and early stage company support. Towards the end of the project, potential commercialisation opportunities will be assessed and where appropriate additional funding sought from for instance the Royal Society Paul Instrument Fund, the EPSRC Follow-on Fund and the Invest Northern Ireland Proof of Concept Programme.