A chance meeting between a spider expert and a chemist has led to the development of antibiotic synthetic spider silk.
After five years’ work an interdisciplinary team of scientists at The University of Nottingham has developed a technique to produce chemically functionalised spider silk that can be tailored to applications used in drug delivery, regenerative medicine and wound healing.
The Nottingham research team has shown for the first time how ‘click-chemistry’ can be used to attach molecules, such as antibiotics or fluorescent dyes, to artificially produced spider silk synthesised by E.coli bacteria. The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) has been published in the online journal Advanced Materials.
The chosen molecules can be ‘clicked’ into place in soluble silk protein before it has been turned into fibres, or after the fibres have been formed. This means that the process can be easily controlled and more than one type of molecule can be used to ‘decorate’ individual silk strands.
In a laboratory in the Centre of Biomolecular Sciences, Professor Neil Thomas from the School of Chemistry in collaboration with Dr Sara Goodacre from the School of Life Sciences, has led a team of BBSRC DTP-funded PhD students starting with David Harvey who was then joined by Victor Tudorica, Leah Ashley and Tom Coekin. They have developed and diversified this new approach to functionalising ‘recombinant’ — artificial — spider silk with a wide range of small molecules.
They have shown that when these ‘silk’ fibres are ‘decorated’ with the antibiotic levofloxacin it is slowly released from the silk, retaining its anti-bacterial activity for at least five days.
Neil Thomas, a Professor of Medicinal and Biological Chemistry, said: “Our technique allows the rapid generation of biocompatible, mono or multi-functionalised silk structures for use in a wide range of applications. These will be particularly useful in the fields of tissue engineering and biomedicine.”
Remarkable qualities of spider silk
Spider silk is strong, biocompatible and biodegradable. It is a protein-based material that does not appear to cause a strong immune, allergic or inflammatory reaction. With the recent development of recombinant spider silk, the race has been on to find ways of harnessing its remarkable qualities.
The Nottingham research team has shown that their technique can be used to create a biodegradable mesh which can do two jobs at once. It can replace the extra cellular matrix that our own cells generate, to accelerate growth of the new tissue. It can also be used for the slow release of antibiotics.
Professor Thomas said: “There is the possibility of using the silk in advanced dressings for the treatment of slow-healing wounds such as diabetic ulcers. Using our technique infection could be prevented over weeks or months by the controlled release of antibiotics. At the same time tissue regeneration is accelerated by silk fibres functioning as a temporary scaffold before being biodegraded.”
The medicinal properties of spider silk recognised for centuries.
The medicinal properties of spider silk have been recognised for centuries but not clearly understood. The Greeks and Romans treated wounded soldiers with spider webs to stop bleeding. It is said that soldiers would use a combination of honey and vinegar to clean deep wounds and then cover the whole thing with balled-up spider webs.
There is even a mention in Shakespeare’s Midsummer Night’s Dream: “I shall desire you of more acquaintance, good master cobweb,” the character ‘Bottom’ said. “If I cut my finger, I shall make bold of you.”
‘I think we could make that!’
The idea came together at a discipline bridging university ‘sandpit’ meeting five years ago. Dr Goodacre says her chance meeting at that event with Professor Thomas proved to be one of the most productive afternoons of her career.
Dr Goodacre, who heads up the SpiderLab in the School of Life Sciences, said: “I got up at that meeting and showed the audience a picture of some spider silk. I said ‘I want to understand how this silk works, and then make some.’
“At the end of the session Neil came up to me and said ‘I think my group could make that.’ He also suggested that there might be more interesting ‘tweaks’ one could make so that the silk could be ‘decorated’ with different, useful, compounds either permanently or which could be released over time due to a change in the acidity of the environment.”
The approach required the production of the silk proteins in a bacterium where an amino acid not normally found in proteins was included. This amino acid contained an azide group which is widely used in ‘click’ reactions that only occur at that position in the protein. It was an approach that no-one had used before with spider silk — but the big question was — would it work?
Dr Goodacre said: “It was the start of a fascinating adventure that saw a postdoc undertake a very preliminary study to construct the synthetic silks. He was a former SpiderLab PhD student who had previously worked with our tarantulas. Thanks to his ground work we showed we could produce the silk proteins in bacteria. We were then joined by David Harvey, a new PhD student, who not only made the silk fibres, incorporating the unusual amino acid, but also decorated it and demonstrated its antibiotic activity. He has since extended those first ideas far beyond what we had thought might be possible.”
David Harvey’s work is described in this paper but Professor Thomas and Dr Goodacre say this is just the start. There are other joint SpiderLab/Thomas lab students working on uses for this technology in the hope of developing it further.
David Harvey, the lead author on this their first paper, has just been awarded his PhD and is now a postdoctoral researcher on a BBSRC follow-on grant so is still at the heart of the research. His current work is focused on driving the functionalised spider silk technology towards commercial application in wound healing and tissue regeneration.
Where will we be in 5 years’ time?
Dr Goodacre said: “It is likely that this paper is just the start of a very exciting range of studies using the new spider silk material. Some of the future work will also be supported by other, neat ideas from the world of spiders and their silk, which the SpiderLab is currently trying to unravel.”
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It was founded as University College Nottingham in 1881 and granted a Royal Charter in 1948.
Nottingham’s main campus, University Park, is situated on the outskirts of the City of Nottingham, with a number of smaller campuses and a teaching hospital (Queen’s Medical Centre) located elsewhere in Nottinghamshire.
Outside the United Kingdom, Nottingham has campuses in Semenyih, Malaysia and Ningbo, China. Nottingham is organised into five constituent faculties, within which there are more than 50 departments, institutes and research centres. Nottingham has around 34,000 students and 9,000 staff and had a total income of £520 million in 2012/13, of which £100 million was from research grants and contracts.
As of 2013 the university was ranked 24th nationally and 174th internationally by Times Higher Education. A 2013 survey suggested it is the second most targeted university by the UK’s top employers.
In 2012 Nottingham was ranked 13th in the world in terms of the number of alumni listed among CEOs of the Fortune Global 500. It is also ranked 2nd (joint with Oxford) in the 2012 Summer Olympics table of British medal winners. In the 2011 GreenMetric World University Ranking, Nottingham was the world’s most sustainable campus.
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Researchers at The University of Nottingham have developed a break-through technique that uses sound rather than light to see inside live cells, with potential application in stem-cell transplants and cancer diagnosis.
The new nanoscale ultrasound technique uses shorter-than-optical wavelengths of sound and could even rival the optical super-resolution techniques which won the 2014 Nobel Prize for Chemistry.
This new kind of sub-optical phonon (sound) imaging provides invaluable information about the structure, mechanical properties and behaviour of individual living cells at a scale not achieved before.
Researchers from the Optics and Photonics group in the Faculty of Engineering, University of Nottingham, are behind the discovery, which is published in the paper ‘High resolution 3D imaging of living cells with sub-optical wavelength phonons’ in the journal, Scientific Reports.
“People are most familiar with ultrasound as a way of looking inside the body — in the simplest terms we’ve engineered it to the point where it can look inside an individual cell. Nottingham is currently the only place in the world with this capability,” said Professor Matt Clark, who contributed to the study.
In conventional optical microscopy, which uses light (photons), the size of the smallest object you can see (or the resolution) is limited by the wavelength.
For biological specimens, the wavelength cannot go smaller than that of blue light because the energy carried on photons of light in the ultraviolet (and shorter wavelengths) is so high it can destroy the bonds that hold biological molecules together damaging the cells.
Optical super-resolution imaging also has distinct limitations in biological studies. This is because the fluorescent dyes it uses are often toxic and it requires huge amounts of light and time to observe and reconstruct an image which is damaging to cells.
Unlike light, sound does not have a high-energy payload. This has enabled the Nottingham researchers to use smaller wavelengths and see smaller things and get to higher resolutions without damaging the cell biology.
“A great thing is that, like ultrasound on the body, ultrasound in the cells causes no damage and requires no toxic chemicals to work. Because of this we can see inside cells that one day might be put back into the body, for instance as stem-cell transplants,” adds Professor Clark.
System has the ability to condition the air and control humidity independently
The University of Nottingham is developing a solar air conditioning system that is said to have the capability to cut electricity consumption by up to 50 percent compared to conventional vapor compression (VC) systems.
Dr. Jie Zhu, from the Department of Architecture and Built Environment at The University of Nottingham, and Professor Tingxian Li, Shanghai Jiaotong University, China, are conducting this research supported by the Royal Society.
The two institutions are investigating a new air conditioning technology, powered by solar energy, whose features include:
• The ability to condition the air and control humidity independently.
• A sorption thermal battery that combines heat and cold energy storage in one unit and has the ability to achieve thermal energy storage with controllable temperature.
Zhu said, “A VC cooling system adopts a condensation dehumidification method to handle both sensible and latent heat loads. This means the system has to operate under lower evaporation temperatures, which results in lower cooling capacity, lower coefficient of performance (COP), and sometimes a reheating process is required to meet supply air requirements.
“We are proposing a temperature and humidity independent control technology to solve this problem. This system can save 25-50 percent electrical consumption and COP increases about 40-60 percent, thus greatly reducing operating costs, compared to the conventional VC system.”
Thermal energy battery storage plays a key role in the use of solar energy for heating and cooling due to solar’s inherent fluctuation and the lack of year-round sun in many countries.
The solid-gas sorption thermal battery has the capability to store both heat and cold energy at a controllable temperature in a single unit. The heat energy is used to power the dehumidification subsystem, while the cold energy is used to cool the air circulating in the indoor environment.
Scientists are trying to find a new way to produce the nutritional fatty acids called Omega 3 that are currently sourced from fish oil from the world’s declining natural fish stocks.
In a groundbreaking branch of new science – synthetic biology – the team at The University of Nottingham’s Synthetic Biology Research Centre are working with biotechnology company CHAIN Biotech and industry partner Calysta, Inc. to develop microbial technology that uses microorganisms to ferment methane gas into valuable nutritional supplements.
The pioneering project is called PUFA (polyunsaturated fatty acids). It will run for a year and is being funded by industrial biotechnology catalyst grants from InnovateUK and the BBSRC with potential further significant scaling up investment from Calysta, a sustainable nutrition company based in the US.
Omega 3 fatty acids are essential for the growth, development and healthy maintenance of the brain and are incorporated in many kinds of foods and infant nutrition products as well as animal feed and health products. Currently Omega 3 fatty acids are sourced from fish oils, but wild fish stocks are under pressure and there is an urgency to find alternative sources that are both sustainable and economical.
If you haven’t already heard of antiferromagnetic spintronics it won’t be long before you do. This relatively unused class of magnetic materials could be about to transform our digital lives. They have the potential to make our devices smaller, faster, more robust and increase their energy efficiency.
Physicists at The University of Nottingham, working in collaboration with researchers in the Czech Republic, Germany and Poland, and Hitachi Europe, have published (14:00 EST Thursday January 14 2016) new research in the prestigious academic journal Science which shows how the ‘magnetic spins’ of these antiferromagnets can be controlled to make a completely different form of digital memory.
Lead researcher Dr Peter Wadley, from the School of Physics and Astronomy at The University of Nottingham,said: “This work demonstrates the first electrical current control of antiferromagnets. It utilises an entirely new physical phenomenon, and in doing so demonstrates the first all-antiferromagnetic memory device. This could be hugely significant as antiferromagnets have an intriguing set of properties, including a theoretical switching speed limit approximately 1000 times faster than the best current memory technologies.”
This entirely new form of memory has a set of properties which could make it extremely useful in modern electronics. It does not produce magnetic fields, meaning the individual elements can be packed more closely, leading to higher storage density. Antiferromagnet memory is also insensitive to magnetic fields and radiation making it particularly suitable for niche markets, such as satellite and aircraft electronics.
If all of this potential could be realised, antiferromagnetic memory would be an excellent candidate for a so-called “universal memory”, replacing all other forms of memory in computing, and transforming our electronic devices.
An expert in environmental toxins at The University of Nottingham has developed a new antifungal technology which has the potential to play a major role in securing future food supplies.
Blocking fungal growth
Professor Simon Avery from the University’s Faculty of Medicine and Health Sciences has discovered that two agents, when combined, affect the process of protein synthesis, and have the potential to effectively block fungal growth in certain types of fungi which cause disease in crops or in humans.
Crop losses due to fungal spoilage each year are equivalent to the amount of food that could feed up to four billion people. In the developed world, millions of tonnes of crops are ruined each year by fungi and the problem is especially acute in developing countries where access to fungicides is more limited.
One of the problems with fungicides is that in many cases, the fungi adapt to the treatment, which means that most fungicides are only effective for a limited period. The solution developed by the University uses two agents which should make it more difficult for the fungi to acquire resistance to the fungicide.
Researchers in bone tissue regeneration believe they have made a significant breakthrough for sufferers of bone trauma, disease or defects such as osteoporosis.
Medical researchers from Keele University and Nottingham University have found that magnetic nanoparticles coated with targeting proteins can stimulate stem cells to regenerate bone. Researchers were also able to deliver the cells directly to the injured area, remotely controlling the nanoparticles to generate mechanical forces and maintain the regeneration process through staged releases of a protein growth stimulant.
The current method for repairing bone that can’t heal itself is through a graft taken from the patient. Unfortunately, this can be a painful, invasive procedure, and when the area that needs repair is too large or the patient has a skeletal disorder such as there can sometimes be a lack of healthy bone for grafting.
Researchers in the United Kingdom and Malaysia are developing a new class of injectable material that stimulates stem cells to regenerate damaged tissue and form new blood vessels, heart and bone tissue.