Author: Natasha Rhys Edited by: Luiz Guidi
If you are a researcher in the life sciences, you may have come across a moment where you wished the equipment you worked with was of a better spec or that you could use a technique not available in your lab. Faced with such problems, one solution that some scientists are turning to is the use of a national facility.
National laboratories provide scientists access to either unique or commonly used state-of-the-art facilities and equipment to advance a research project. Such facilities can be found at various sites around the globe and cater for a diverse range of fields, including space science, engineering, computing, healthcare, energy and the environment. For life sciences, a national facility can provide additional space and equipment to complete experiments or may host large-scale instruments that are not realistic to have in the realms of a normal research group lab. In 2014, the UK proposed to contribute 165 million GBP to the development of the European Spallation Source in Scandinavia, a collaborative effort between numerous European countries to build a facility for experiments using neutrons. Neutrons, which can only be produced at a specialised facility, are used to study the structure, dynamics and interactions of biological systems and are highly sensitive to hydrogen atoms.
If travelling to a global location seems far-fetched, UK science benefits from its own national facilities, including the Harwell Campus. This site is home to around 200 research organisations, including a neutron source, a synchrotron for techniques using X-ray, infrared and ultraviolet radiation, a laser facility, specialised laboratories for focused disciplines such as genomics, and numerous other research complexes to support scientists and increase the opportunity for collaborations. Many of the facilities on the site are funded by research councils such as the Science and Technology Facilities council (STFC) and the Medical Research Council (MRC).
As onsite technology improves, facilities like those at Harwell are becoming more commonly used for high-impact research in life sciences. For example, an article published in Nature Communications at the end of October 2016 reports work that used the site’s Central Laser Facility (CLF). The CLF houses a specialised biophotonics suite of instruments dedicated to the detection and super-resolution imaging of biological matter. Using fluorescence lifetime imaging, the authors challenged the view on how proteins involved in controlling the growth of cells, known as Epidermal Growth Factor Receptors, transmit signals to each other. The work instead supported a newer theory that signalling occurs through clusters of receptors instead of just between two individual ones. As disruption to the signalling between receptors can cause cancer, this work highlights the complexity of this system for developing treatments. “The work in this article was made possible using the cutting-edge, non-commercial instrumentation developed here at the site”, says Professor Stanley Botchway, an advanced-imaging senior scientist at the CLF and the multidisciplinary Research Complex at Harwell. “Doing work onsite at the facility means I regularly interact with researchers from many disciplines; one moment I’m talking to a biomedical scientist, the next to a physicist, chemist or engineer. This helps to enhance and foster new ways of thinking about a problem”.
Even at established sites like Harwell there is innovative technology being consistently developed or introduced. For drug discovery, a collaboration with the Diamond Light synchrotron source and the Structural Genome Consortium of Oxford saw the introduction last year of the Xchem unit for fragment-based screening of compounds. This type of screening consists of studying with X-ray crystallography how smaller ‘fragments’ of novel drugs interact with a target protein, though to harvest crystals and measure data on hundreds of promising compounds usually takes months. By building Xchem, which has made the stages more streamlined and automated, screening hundreds or thousands of compounds now takes a matter of days. As well as supporting fundamental biomedical research, Xchem is proving to be an invaluable resource for pharmaceutical companies.
Innovative technology developed onsite at a facility has also been commercially available. Cobalt Light Systems is a spin-out company of CLF using Raman technology developed onsite that supplies products for non-invasive chemical analysis. Their products are being used in the pharmaceutical and chemical industries and are also involved in clinical trials for bone density scanning as well as detection of breast cancer tissue.
These instruments have become more readily accessible to academic researchers who can usually apply for funded time. This has led to the inaccurate impression that organisations like those at Harwell do not host industrial users. One successful example is work by Heptares Therapeutics that was featured on Channel 4 news in 2013. The company specialises in the development of drugs that target G-protein Coupled Receptors that are responsible for transferring chemical signals to cells. Using instrumentation at Diamond Light Source, the company was able to determine the crystal structure of a receptor linked with the development of depression and stress. Knowledge of the structure is vital in identifying novel drug molecules to target these conditions.
There is a growing interest in encouraging more industrial users to conduct experiments at these facilities to encourage the development of instrumentation through new collaborations and increase the range of high-impact science that takes place onsite. There are multiple routes available for companies to obtain instrument time. For a company with expertise in a particular technique, they can pay for time on the instrument directly. For novices, there are often options available to try out a technique to test its benefit to a research project. Facilities such as Diamond offer a consultative approach where a dedicated team can take a company through the stages of conducting research at the synchrotron, from initially advising on the best techniques to use for a project to completing the experiment on their behalf. This scheme has resulted in up to 20% of proposals for beam time at Diamond having some connection with industry.
So if you are a researcher from academia or industry, longing to get that structure you don’t have the facilities to resolve, that image you wish you had better resolution on, or maybe the opportunity to develop new technology to support the work in your laboratory, why not check to see if a national facility could help?