The latest issue of the ISTM Translate magazine is now available in digital and print format. The theme focus for this issue is nanopharmaceutics.
There are contributions from Dr Clare Hoskins, Dr Anthony Curtis, as well as other members of the Keele Nanopharmaceutics Group. Articles include...
· Medicine at the small scale: The exponential growth in nanopharmaceutics
· Programming death in cancer cells: Novel technologies improving long-term prognosis
· The great solubility challenge: Investigating potential in targeted drug delivery
· Theranostic Advances: The knowledge and fabrication of nanotechnologies
· Nanopharmaceutics Symposium: Successful second annual event at Keele University
· Spotlight: The people behind ISTM
· Public engagement: Bringing research closer to people
· Taking advantage of change: A new streamlined Institute structure for ISTM
By clicking here you can access the online digital version of Translate Issue 4. Alternatively you can request a paper copy by contacting: Joseph Clarke +44 (0)1782 674998 | j.clarke@keele.ac.uk
Written by Dr David Mottershead (Lecturer in Biochemistry & Cell Biology, ISTM) ********************************
Making new friends from the Congress. (David is second from right).
As a result of an email I received on the 20th of June this year inviting me to speak at the Royan International Twin Congress (August 31-September 2) in Tehran, Iran, I was plunged into quite an adventure. The Royan International Twin Congress has been held every year since the first meeting in September 2000. This year’s meeting saw the joint holding of the 17th Congress on Reproductive Biomedicine and the 12th Congress on Stem Cell Biology & Technology, both supported and organized by the Royan Institute in Tehran. This being my first trip to the middle east meant that a new and unusual experience was assured.
Ceiling of the Tomb of Hafez, Shiraz.
The meeting itself reflects the nature and makeup of the Royan (in Persian “royan” means embryo) Institute itself, which has Divisions devoted to reproductive biomedicine, stem cell biology and biotechnology. The congress itself has the two streams of reproductive biomedicine and stem cell biology running concurrently. This enabled one to pick and choose between both session streams, and although I found myself predominantly within the reproductive stream, I did cross over for a number of very interesting presentations within the stem cell stream as well. International speakers from across the world were in attendance (UK, USA, Austria, China, Netherlands, Australia, Germany, Denmark, Sweden, Switzerland, Italy, for example). Apart from Keynote Lectures and Award Lectures, there were the various invited speakers talks, short oral presentations, poster sessions and exhibitions. The sessions of particular interest to me were, Animal Biotechnology, Tissue Engineering in Reproductive Sciences, and Regenerative Medicine, Novel Discoveries.
Tombs of kings past, Naqsh-e-Rostam.
The conference organizers looked after the invited speakers extremely well, we were never short of food/refreshments at the venue and every evening we were taken to see sites in Tehran and out to eat, enabling us to experience the magnificent local cuisine. From my own point of view, the congress was extremely productive with good discussions/connections established between myself and two separate labs at the Royan Institute which should lead to ongoing collaborations. For all the invited speakers a 2 day tour of highlights of Iran was offered which I participated in, enabling one to experience the history of the country and see some amazing sites. First we flew South to Shiraz, a distance of 700 km. We arrived late and would not have time to get to know Shiraz well, but did visit the Tomb of Hafez, one of Iran’s famous and revered poets who lived in the 14th century (1325-1389). Upon leaving Shiraz by bus we started our long trip back North to Tehran. Our first stop 70 kms from Shiraz was at a series of tombs cut into the cliff side where ancient kings were buried. The site is known as Naqsh-e Rostam and had a distinctly “Indiana Jones” feel to it, certainly it transported one back in time. Not far from this site we stopped at the ruins of the ancient city of Persepolis which was the ceremonial capital of the Achaemenid Empire (550–330 BC). Here various kings and statesmen from around the world would come to greet the Iranian king, a must see site on any trip to Iran. Finally we arrived at the city of Esfahan (also spelt Isfahan) about 300 km South of Tehran. Esfahan is the 3rd largest city in Iran at nearly 2 million people. The main attraction is the large Naghsh-e-Jahan square constructed between 1598 and 1629. Around the square are located three mosques and what seems like hundreds of shops selling the most beautiful craftworks. I could not do this area justice in this short visit, however, given the collaborative links which I believe will be established, it may well not be my last.
One of the mosques at Naghsh-e-Jahan Square, Esfahan.
I was surprised and delighted to find a couple of weeks ago that I had been awarded the Vice-Chancellor’s PhD Prize 2016 for the best postgraduate research at the University of Greenwich.
My programme of research was Understanding MS/MS Fragmentation of Small Molecular Weight Molecules. I proved the hypothesis that protonation altered the conformation of molecules such that some bonds were weakened and more susceptible to cleavage. This impacts all scientists who use MS/MS for structural elucidation in that quantum chemistry can now be used a tool in assignment of ion structures. I am pleased to have been able to make a real difference to UK science.
I loved every minute of my PhD, particularly the stimulating scientific discussions with my supervisor Professor Frank Pullen and computational chemistry expert Alexander Alex. I also enjoyed getting to grips with quantum chemistry.
Thanks to the support and encouragement of the staff in the Greenwich University Department of Pharmaceutical, Chemical and Environmental Sciences, I managed to take my viva voce one day before the third anniversary of starting my research programme, passing with no changes required to my thesis and having published five research papers and two editorials. I am also grateful for the tolerance of my family who put up with me working all the time!
Patricia has since come to work at Keele University for ISTM in the breath analysis research group pioneered by Professor David Smith FRS.
Friday, 2 September 2016
How brain implants can let paralysed people move again
Dimitra Blana, Keele University and Andrew Jackson, Newcastle University
Something as simple as picking up a cup of tea requires an awful lot of action from your body. Your arm muscles fire to move your arm towards the cup. Your finger muscles fire to open your hand then bend your fingers around the handle. Your shoulder muscles keep your arm from popping out of your shoulder and your core muscles make sure you don’t tip over because of the extra weight of the cup. All these muscles have to fire in a precise and coordinated manner, and yet your only conscious effort is the thought: “I know: tea!”
This is why enabling a paralysed limb to move again is so difficult. Most paralysed muscles can still work, but their communication with the brain has been lost, so they are not receiving instructions to fire. We can’t yet repair damage to the spinal cord so one solution is to bypass it and provide the instructions to the muscles artificially. And thanks to the development of technology for reading and interpreting brain activity, these instructions could one day come direct from a patient’s mind.
We can make paralysed muscles fire by stimulating them with electrodes placed inside the muscles or around the nerves that supply them, a technique known as functional electrical stimulation (FES). As well as helping paralysed people move, it is also used to restore bladder function, produce effective coughing and provide pain relief. It is a fascinating technology that can make a big difference to the lives of people with spinal cord injury.
Dimitra Blana and her colleagues at Keele are working on how to match this technology with the complex set of instructions needed to operate an arm. If you want to pick up that cup of tea, which muscles need to fire, when and by how much? The firing instructions are complicated, and not just because of the large number of core, shoulder, arm and finger muscles involved. As you slowly drink your tea, those instructions change, because the weight of the cup changes. To do something different, like scratch your nose, the instructions are completely different.
Instead of just trying out various firing patterns on the paralysed muscles in the hope of finding one that works, you can use computer models of the musculoskeletal system to calculate them. These models are mathematical descriptions of how muscles, bones and joints act and interact during movement. In the simulations, you can make muscles stronger or weaker, “paralysed” or “externally stimulated”. You can test different firing patterns quickly and safely, and you can make the models pick up their tea cups over and over again – sometimes more successfully than others.
Modelling the muscles
To test the technology, the team at Keele is working with the Cleveland FES Center in the US, where they implant up to 24 electrodes into the muscles and nerves of research participants. They use modelling to decide where to place the electrodes because there are more paralysed muscles than electrodes in current FES systems.
If you have to choose, is it better to stimulate the subscapularis or the supraspinatus? If you stimulate the axillary nerve, should you place the electrode before or after the branch to the teres minor? To answer these difficult questions, they run simulations with different sets of electrodes and choose the one that allows the computer models to make the most effective movements.
Currently, the team is working on the shoulder, which is stabilised by a group of muscles called the rotator cuff. If you get the firing instructions for the arm wrong, it might reach for the soup spoon instead of the butter knife. If you get the instructions to the rotator cuff wrong, the arm might pop out of the shoulder. It is not a good look for the computer models, but they don’t complain. Research participants would be less forgiving.
Knowing how to activate paralysed muscles to produce useful movements like grasping is only half of the problem. We also need to know when to activate the muscles, for example when the user wants to pick up an object. One possibility is to read this information directly from the brain. Recently, researchers in the US used an implant to listen to individual cells in the brain of a paralysed individual. Because different movements are associated with different patterns of brain activity, the participant was able to select one of six pre-programmed movements that were then generated by stimulation of hand muscles.
Reading the brain
This was an exciting step forward for the field of neural prosthetics, but many challenges remain. Ideally brain implants need to last for many decades – currently it is difficult to record the same signals even over several weeks so these systems need to be recalibrated regularly. Using new implant designs or different brain signals may improve long-term stability.
Also, implants listen only to a small proportion of the millions of cells that control our limbs, so the range of movements that can be read out is limited. However, brain control of robotic limbs with multiple degrees-of-freedom (movement, rotation and grasping) has been achieved and the capabilities of this technology are advancing rapidly.
Finally, the smooth, effortless movements that we usually take for granted are guided by rich sensory feedback that tells us where our arms are in space and when our fingertips are touching objects. However, these signals can also be lost after injury so researchers are working on brain implants that may one day restore sensation as well as movement.
Some scientists are speculating that brain-reading technology could help able-bodied individuals to communicate more efficiently with computers, mobile phones and even directly to other brains. However, this remains the realm of science fiction whereas brain control for medical applications is rapidly becoming clinical reality. Dimitra Blana, Research Fellow in Biomedical Engineering, Keele University and Andrew Jackson, Wellcome Trust Senior Research Fellow, Newcastle University
This article was originally published on The Conversation. Read the original article.
ISTM recently ran a blog writing competition that was open to PhD students and young researchers with a view to improving their lay-writing skills and helping ISTM to play a greater role in the public dissemination of its research. After concluding the competition we will be publishing each entry in turn over the coming months. The 2nd prize winner of our competition was Homayemem Weli, a PhD student in Cell and Tissue Engineering at ISTM.
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Walking through the streets of London in mid-summer, I couldn’t help but notice its beautiful 'ornaments' of modern architecture, such as the "Gherkin" or the "Walkie-Talkie". Imposing as these are, they attract less curiosity than Wiltshire’s Stonehenge.
A graceful and strong modern building speaks of a firm foundation and good design, but an ancient monument raises questions such as "when", "how" and "why". Some of us recall the creation of the London skyscrapers - having possibly witnessed it - but I dare say none of us witnessed the making of Stonehenge! Instead, we rely on archaeological research to answer questions about its origin, age and significance. This ‘discovery science’ compels us to find out why things are the way they are, and go from the known to the unknown.
Stonehenge by David Ball -
www.davidball.net
Keen to unravel the unknown, I set out to study an aspect of why people age. My focus was on women and what happens to their vaginal and skin tissues before and after pregnancy. Adorned with laboratory clothing and gloves, as though performing carbon dating on the standing stones of Stonehenge, I examined the structure of collagen fibres and cross-links within the tissues. Collagen is a protein that supports structures within the body. Cross-links are bonds formed between collagen groups (called fibres) or between chemical substances such as amino acids or reducing sugars. The larger the number of certain cross-links within the collagen fibres, the older the fibres. Collagen 'cross-link dating' can separate old fibres from young ones.
I tested two groups of tissues, pregnant and non-pregnant, of similar biological ages. I separated a particular cross-link, pentosidine, which is a known marker of tissue ageing, from the tissue solutions with liquid chromatography (a method for identifying and separating substances present within a solution). I noted the amount of pentosidine in each tissue, and compared the values.
This process of 'cross-link dating' separated the age-matched tissues into two groups – ‘old’ and ‘young’. Before pregnancy, tissues were ‘older’, but after pregnancy, they appeared ‘younger’. During pregnancy, the signs of ageing appeared to reverse!
Studying further, I discovered this was linked with a rise of a potent antioxidant, glyoxalase I, in the tissues during pregnancy. Antioxidants such as glyoxalase I protect the body cells from molecules that could cause damage or promote ageing.
Antioxidant glyoxalase I enzyme
expression in vaginal tissues during (left) and after (right) pregnancy. Green
glow, clearly visible within the pregnant tissue, represents presence of the
antioxidant enzyme. The pregnant tissues had more antioxidant.
Oestrogen, a well-known pregnancy hormone, influenced the amount of the antioxidant in the tissues. I found higher oestrogen levels in pregnant tissues as shown in the images below. This implied pregnancy resulted in higher oestrogen and antioxidant levels.
Oestrogen receptor expression in vaginal
tissues during (left) and after (right) pregnancy. Red dots signify oestrogen
activity within the tissue and show raised level of oestrogen during pregnancy.
I concluded that oestrogen influences the ‘age’ of collagen fibres of the skin and vaginal wall by increasing the antioxidant glyoxalase I. Rise in oestrogen as seen in pregnancy leads to rise in the enzyme, subsequently retarding collagen fibre ageing within the tissues. In this way, pregnancy results in younger appearing tissues.
Oestrogen is a female reproductive hormone that changes throughout the life of a woman. It increases in quantity during pregnancy and reduces as women grow older, finally reaching its lowest levels in menopause. My finding shows that pregnancy may retard this ageing process in the vaginal and skin tissues of women. A previous study noted a reduction in similar ageing cross-links within blood vessels also in association with higher oestrogen levels, suggesting that this effect may exist in many body tissues.
By studying pregnancy, I discovered a relationship between oestrogen, an antioxidant, and the ‘age’ of collagen fibres (change of the structure) in skin and vaginal tissues.
New knowledge can be gained from investigating age-old body processes. It's always worth asking "when", "how" and "why”!
Written by Homayemem Weli, PhD Student, ISTM (2nd Prize in the ISTM Blog Post Competition 2016)
This is a meeting for people who work in the area of shoulder biomechanics. We try to understand how the shoulder works, what goes wrong after injury or disease, how to improve its movement in sport, and how to protect it in well-designed work environments. For those of us doing shoulder research (and probably nobody other than us) it is a fascinating topic, and we look forward to getting together every couple of years and discussing it.
My particular focus is mathematical modelling of the shoulder. Using models allows us to investigate how muscles and joints work without invasive procedures on actual people. It is a very useful tool, and one of the ways we use it is to design technological systems that tackle paralysis.
Co-presenter Ricardo Matias (University of Lisbon) during the modelling workshop
As part of the International Shoulder Group meeting this year, I ran a modelling workshop that aimed to introduce modelling to people who have not used it before. The response was very positive, and everyone seemed keen to give it a go. With participants from 13 different countries, it is great to know that our models could be used all over the world!
Dimitra and her thank-you gift for helping to organise the conference
Shoulder biomechanists are such a lovely lot, and I can’t wait to see everyone again in 2018!
ISTM recently ran a blog writing competition that was open to PhD students and young researchers with a view to improving their lay-writing skills and helping ISTM to play a greater role in the public dissemination of its research. After concluding the competition we will be publishing each entry in turn over the coming months. The 1st prize winner of our competition was Fraser Philp a PhD student at ISTM. Fraser's PhD focuses on identifying within current practice and research, methods used for predicting injury and performance within football and Fraser used this topic as the theme for his blog post.
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Association football or soccer is one of the most popular international sports, with approximately 200,000 professionals and a further 240 million amateur male and female participants worldwide. Football is England’s largest national team sport, with men’s and women’s football being the first and third largest team sports respectively. Associated with the high levels of participation in football is a high level of injury risk. As many as 47% of footballers have been forced to retire from the game due to injury throughout the season, an average outfield player is expected to sustain at least 1-2 injuries resulting in them being unavailable for 1 competitive game. High rates of injury can negatively impact on the performance of an individual. Likewise an increased number of individuals sustaining injury within a team can negatively affect team performance, which, in a competitive league can have further consequences.
Given the problems associated with injury, the medical and sports science teams who work with professional football teams try to minimise injuries occurring. One of the ways they attempt to do this is through screening. Screening can involve exercise tests and measures of physical performance that are used in an attempt to identify injury risk factors. These tests are usually carried out before the competitive season starts, in a period known as pre-season, and during the competitive season itself. Despite the widespread use of these tests and measures, many of them have not been and compared against other methods of measurement for validation purposes.
Motion capture is more widely known for its use in the movie industry in virtual recreation. It is also used as the gold standard measurement in hospital settings for measuring walking patterns and human movement patterns in people with neurological disorders. In order to measure the movements of the FMS with motion capture cameras, some additional preparation is needed. This requires placing reflective markers on selected body parts of the person. This is because the motion capture camera’s only pick up reflections from the infrared light that they send out. These markers can then be virtually recreated providing an outline of the person’s body parts on which they were placed. Once this has been done we are able to see the angles achieved by the participant in all 3 dimensions i.e. how much they bent their knee or how much their hip was rotating. It also allows for a description of the movement patterns that are occurring across the joints when the participant completes the FMS. Furthermore we can also attribute numerical values to the rules and scoring criteria of the FMS exercise tests.
Figure above shows the process after placing the markers on and then virtualy recreating them.
Alongside this we have monitored a football team over one competitive season and will investigate whether there is a link between the measurements we took and the injuries they sustained. Within this analysis we will also be investigating things such as the amount they trained, the surface they trained on and what their match fixtures were like. Hopefully a better understanding of all these factors will allow for fewer injuries in footballers.
Written by Fraser Philp, PhD Student, ISTM (1st Prize in the ISTM Blog Post Competition 2016)
