29/11/04 - Status of MPW 6.2 Beamline
29/11/04 - Status of MPW 10.1 Beamline
29/11/04 - High Throughput Protein Screening Service
from DARTS
15/11/04 - 4GLS Industry Meeting
04/11/04 - DARTS Cracks the Crystal Haze
29/09/04 - DARTS improves process control through
formulation characterisation
09/09/04 - DARTS meets the challenge in complex crystal
structure determination
Come and join our DARTS staff at events in 2004
29/11/04 - Status of MPW6.2 Beamline
MPW6.2 is one of the most recently commissioned beamlines on the SRS and has been optimised to be particularly powerful for the investigation of structural changes during time-resolved materials processing experiments. The principal characteristics of the beamline are:
The beamline also benefits from an advanced GUI-based integrated software control system for data acquisition and sample environment manipulation.
A wide range of experiments have been successfully performed on the station since it opened for general use in 2003. It is one of the most over-subscribed beamlines on the SRS, further demonstrating the powerful nature of the combined techniques approach to materials characterisation problem solving.
29/11/04 - Status of the MPW MAD 10 Beamline
The new MPW MAD10 beamline has successfully completed its commissioning program during AP42 (March-October 2004). The station is characterized by the new MAR desktop beamline (DTB) with CryoSampleChanger capable of storing up to 19 samples at time. The DTB has been integrated with the MAR225 Mosaic detector for macromolecular crystallography and by the C-TRAIN solid state fluorescence detector for MAD/EXAFS experiments (see figures below).
The commissioning period has been characterized by many research highlights including the following:
In May 2004 the our ability to scan any absorption edge between 0.9-2.5 Å was used by Dave Stuart's group from Oxford University to clearly identify manganese (Mancini EJ et al, Cell, 118,743-55 (2004)) and by RB Williams from LMB-MRC (Cambridge, UK) to locate sulfur atoms by anomalous diffraction (Developmental Cell, 7, 559-569 (2004)).
Structures at atomic resolution are such sought after and have become the "Gold Standard" for structure determination. The first atomic structure on beamline 10 was achieved on Azurin II, which is implicated in the donation of electrons to nitrite reductases in denitrifying bacteria. Several azurin II structures have already been published; however Paraskevopoulos et al. from Daresbury Laboratory were able to collect the first atomic resolution structure of the protein.
This work confirmed that MPW10 is providing users with the brightest beam at SRS. An industrial group collected data on MPW10 as part of a benchmarking effort on the new beamline. They were able to extend the resolution of their data set to 1.9Å compared to data collected on 14.2, where very similar crystals diffracted to 2.3Å.
So far two new structures have been solved by Se-MAD. One of these is from Dr. Fusinita van den Ent and Dr. Jan Lowe (LMB-MRC) the first group to test the MAD capability of MPW10. They collected data overnight on Friday and by the evening of the following Sunday they were able to state 'The structure is basically solved. The native is 2.8 Å, we couldn't get anything better, but that should be enough. The density is gorgeous!'
Overall the output for MPW10 during its commissioning time is of 2 new structures
solved by Se-MAD (unpublished), 1 new structure solved by molecular replacement
(unpublished), 2 high impact pubblications for work on anomalous scatterers,
and 2 high resolution structures (unpublished), plus other data collected.
29/11/04 - High Throughput Protein Screening Service from DARTS
The introduction last year of a full turnkey operation for screening protein structures for identification of drug candidate molecules has been so successful that the DARTS team is expanding its workforce to cope with increased demand. The service includes full data collection, analysis and reporting - all in record time.
The first stage in the process is crystallisation where, after purification and characterisation, the protein-drug complex is crystallised for structure-based optimisation studies into binding and drug candidate identification. The DARTS team uses state-of-the-art robotics and its many years of experience to rapidly ascertain the conditions required for crystallisation of proteins to diffraction quality.
Structure determination uses the facilities of the Daresbury Laboratory synchrotron
and the expertise of DARTS scientists, to obtain a far higher resolution
X-ray diffraction pattern than is possible with conventional laboratory X-ray
equipment. This allows for rapid determination of the protein crystal structure,
reducing the initial screening operation from months to weeks - a highly attractive
proposition in early stage drug discovery.
Invaluable to smaller biotech companies with limited resources, the DARTS
service is also of interest to established pharmaceutical companies who recognise
the advantages of outsourcing to such a service. Work can be tailored to specific
projects in support of a company's in-house research team, helping to reduce
the time and costs involved in screening drug candidate and target molecules
at an early stage in the discovery process.
15/11/04 - 4GLS Industry Meeting
The first 4GLS Industry Meeting was held at the Radisson Edwardian Hotel in Manchester on 23rd September 2004. The lively meeting attracted over 70 delegates representing firms interested both in the advanced technology required for 4GLS and the scientific exploitation of 4GLS. Application areas represented were particularly diverse spanning pharmaceuticals, through skin care products to nano materials and catalysis.
The day, which was chaired by John Garside (VC, UMIST), opened with thought-provoking presentations from Andrew Leslie (LMB Cambridge), John Stageman (AstraZeneca) and David Hughes (DTI). These laid the foundations for discussion and debate on the general issues of linking activities and emerging techniques to emerging markets, innovation, exploiting the electromagnetic spectrum, international competitiveness and long term development potential. The technical characteristics of 4GLS were presented by 4GLS Team members and then the meeting split into three parallel sessions to discuss, in detail, the specific challenges and opportunities presented by 4GLS in the areas of pharmaceuticals, catalysis and semiconductors. Feedback from the parallel sessions fostered further wide-ranging discussions, complemented by a presentation from Alan Todd (AES and Chair of the Industrial Advisory Board for the Jefferson Laboratory FEL) on the approaches taken to foster industrial use of the JLab FEL. The day closed with a question and answer session followed by an excellent meal.
The meeting was followed on the 24th of September by tours of Daresbury Laboratory. These were well attended and covered not only the site for the ERL prototype but also SuperSTEM, HPCx, DARTS and the SRS linac, booster and main ring. The tours finished with lunch in the atrium of the new Daresbury Innovation Centre.
The meeting was organised and sponsored by the NWDA and much credit should go to Pamela Harbron (NWDA) for her hard work over many months.
04/11/04 - DARTS cracks the crystal haze
The cause of the haziness affecting a transparent polymer food packaging material was discovered by DARTS by combining two complementary techniques available on the synchrotron.
Transparent packaging suits both consumers, who can see what they are buying, and manufacturers who can use the visual appeal of the product to entice the customer. However, if the package looks imperfect or deteriorates in storage then this advantage is negated.
The polymer film in question consisted of a core of polypropylene with a 0.6 micron surface layer of random copolymer of propylene and ethylene. The haze effect was known to be caused by the scattering of light from crystallites, but more information about the exact nature and size of these crystallites was needed in order to eradicate the problem.
The use of Grazing Incidence X-ray Diffraction (GIXD) allowed the molecular arrangement of the coating layer alone to be examined. The X-rays are directed at a very shallow angle through the surface and are diffracted without penetrating the core material. The results revealed that despite the presence of ethylene in the coating film there was still a significant degree of crystallisation occurring with crystal sizes large enough to scatter visible light.
Small Angle X-ray Scattering (SAXS) used on the bulk material showed that hazy samples contained crystallites of around 200 Angstrom in size.
The DARTS team's ability to access and combine a range of complementary techniques provides information to help manufacturers control processing conditions and modify manufacturing techniques to improve a wide range of products. Even the everyday crisp packet has benefited from DARTS leading edge technology.
29/09/04 - DARTS improves process control through formulation characterisation
Using the skill and expertise of the DARTS team and the high intensity X-rays produced by the Daresbury synchrotron, a major player in the oil industry has been able to improve the formulation control of its oil additive quickly and effectively.
Inorganic particles coated with detergent are added to lubricant oils to prevent corrosion and to enable the oil to achieve the desired long-term lubrication performance. The additive neutralises acidic by-products from fuel combustion and acids formed by oxidation and degradation of the oil. Designing the optimum formulation required detailed characterisation of the structure of the detergent additive in a timescale that minimised loss of production.
Using small angle X-ray scattering (SAXS), the DARTS team were able to determine particle size, shape and size distribution in a range of oil formulations with different particle/detergent compositions of the additive. DARTS researchers overcame the difficulties of interpreting the subtle changes arising despite a weak signal to noise ratio - often a limitation of laboratory X-ray equipment. Typical particle sizes of 2050 Å were easily accommodated by the SAXS analysis which can be used effectively on sizes as low as 10 Å.
Accurate characterisation of formulation is the essential bridge linking tight
process control to reliable product performance. The speed and high quality
results which SAXS produced saved the company lost operating time and preserved
their reputation by ensuring optimisation of the product and its manufacturing
process. Manufacturers across a range of industries including plastics, cosmetics
and food could improve their products and processes by acquiring detailed information
on formulation structures through DARTS.
09/09/04 - DARTS meets the
challenge in complex crystal structure determination
Patients in the future may be recovering much more quickly from surgery with the introduction of a new molecule which suppresses the effects of the neuromuscular blockers often used in conjunction with anaesthetics.
Researchers from the drug development company Organon have been investigating the idea of creating a molecule that will 'cage' the blocking drug to suppress its action post-operatively, thereby allowing much faster patient recovery.
They achieved the desired action but in order to confirm the mode of interaction within the blocker complex it was necessary to identify the structure - impossible with conventional laboratory X-ray diffraction methods.
Working with scientists from DARTS they were able to 'see', for the very first time, the structure of this new molecule in the detail they needed. DARTS provides access to the Synchrotron Radiation Source (SRS) with 1000 times the intensity of standard X-ray equipment. The combination of small crystal size and large molecular structure presented a major challenge but using SRS and advanced computational methods, DARTS revealed the secrets of the structure.
The determination of complex crystal structures by DARTS has also led
to important breakthroughs for researchers in many other industrial applications.
DARTS has helped solve problems across a broad spectrum of industries
including catalysis, pigments, minerals and chemicals as well as the pharmaceutical
application detailed here.
Come
and join our DARTS staff at events
in 2004
Dr Chris Pickles will attend the IMechE Nano Conference on the 9th of December in Maidenhead.
Dr Elizabeth MacLean and Dr Fariba Bahrami will present a poster at the CEFIC/RCUK Toxicogenomics meeting in Brussels on the 16th of November.
Dr Chris Pickles will attend PABORD in London on the 28-29th September.
Dr Elizabeth MacLean will give a presentation at the annual SR
Users Meeting on 15th September at Milton Hill House, Oxfordshire.
Professor John Helliwell will attend the 22nd
European Crystallographic Meeting, on 26th -31st August in Budapest.
Dr Chris Pickles and Dr Graham Bushnell-Wye will attend ChemSpec Europe, on 23rd-24th June in Amsterdam.
Dr Elizabeth MacLean will give a presentation at TheNanoMicroClub,
on 24th June at Daresbury Laboratory.
Dr Elizabeth MacLean and Dr Chris Pickles will attend the Chemicals Northwest Car Boot Services Sale, on 10th June in Warrington.