Tissue "archeology": Dating collagen fibers

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)

ISTM at the International Shoulder Group meeting

A few weeks ago I went to Winterthur, Switzerland to meet a group of old friends. It wasn’t a holiday; I was there for the biennial meeting of the International Shoulder Group, a technical group of the International Society of Biomechanics.

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!

Predicting injury in football

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.

http://www.bbc.co.uk/sport/football/36189778

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. 

My research project is aimed at comparing and providing numerical values to one of the exercise screening tests that is commonly used. The screening test being evaluated is the Functional Movement Systems (FMS) screen, and I will be using a video motion capture system, Vicon (©Vicon Motion Systems Ltd) for my evaluation. The FMS is partly made up of 7 exercise tests, in which the participant is required to complete the movements, a maximum of 3 times. These tests include things such as a squat with their arms above their head, lunges and other physical tests. The quality of the movements is then scored by an assessor and the participant is given a score for each test. The final score is then used to identify injury risk, with a lower score indicating a higher risk of injury. I have chosen to evaluate the FMS against a motion capture system as this has not been done yet and there are some limitations experienced when using the FMS test. The movement test takes into consideration some patterns of movement but does not describe the angles that are achieved at the joints. It is also difficult for the person assessing to observe multiple joints, whilst at the same time, scoring the movement and identify variations in movement patterns. These problems arise because the assessor has essentially a limited 2 dimensional view and of a complex dimensional. The use of motion capture can help with some of these challenges.

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)

Major funding boost for Stroke Research

Professor Christine Roffe

Professor Christine Roffe, Consultant in Stroke Medicine at the Royal Stoke University Hospital and Lead of the Stroke Research in Stoke Group at ISTM, has been awarded a major grant to fund a £2.5 million project from the NHS National Institute for Health Research (NIHR) Health Technology Assessment Programme for her MAPS-2 clinical trial.

Professor Roffe has a proven track record in shaping the development of acute and rehabilitation stroke services in North Staffordshire, with research that has gone on to influence regional and national practices in stroke care.  As Principle Investigator, Professor Roffe will lead a consortium which includes Keele University in collaboration with the University Hospitals of North Midlands (UHNM), the University of Birmingham and Anglia Ruskin University.  The consortium will investigate methods to reduce pneumonia in stroke patients.

Pneumonia is a major cause of death and disability after stroke.  Stroke patients are at risk of contracting pneumonia through the inhalation of saliva or gastric content after vomiting or regurgitation which contain harmful bacteria.  This award from the NIHR will fund clinical trials that will test two methods for preventing pneumonia. One will aim to prevent patients vomiting in the first place, while the other will use an antibacterial paste in the patient’s mouth to reduce the harmful bacteria in their saliva.

Professor Roffe said that:  “Pneumonia after stroke weakens patients and delays recovery. In this trial we are hoping to show that these treatments not only prevent pneumonia and death, but also allow patients to recover better and faster.”

The trial will begin to recruit patients in October 2016 and run for three years.  If the treatments prove effective, lives could be saved and stroke patients may stand a better chance of getting back to their normal life in a shorter space of time.

Matt Dunn wins I’m A Scientist Get Me Out Of Here!

I’m A Scientist Get Me Out Of Here is a competition in the vein of I’m A Celebrity Get Me Out Of Here, where several people compete for a prize and each week, one of them is evicted until only one remains. Luckily ISTM's Matt Dunn didn’t need to go to the jungle as I’m A Scientist takes place entirely online at http://imascientist.org.uk/ .  Beating off  fierce competion, Matt went on to win the competition.  So, we asked Matt to tell us a little bit more about his experience...

The competition ran from 13th to 24th June, where scientists with successful applications were split into different ‘Zones’ depending on their field, I was put into the ‘Cells Zone’ with four other cell biologists. For the next two weeks, we took part in numerous 30 minute live-chat sessions with classes of students from twenty different secondary schools, ranging from Year 7 to Year 9, all across the country. In these live chats the students could ask us anything they liked, from the work we did, to describing an average day, to what our favourite foods were! Despite the casual nature of the chats, the students can really test your knowledge of your subject, making it a great challenge.

Outside of the live chats, students can ask you questions directly on a profile, and they vote for their favourite scientist. Scientists with the least votes were evicted every day for the last five days until only one was left. I was lucky enough to be the last scientist standing, winning £500 to spend on outreach activities!

I plan to use the money to raise awareness of the great regenerative medicine work we all do here at ISTM, as part of the HEART Outreach group. We usually attend a few fairs and events a year as exhibitors, to spread the good word, but with the prize money we will be able to travel further and better show off the quality of the work we do here with improved cutting-edge technology.

I’m A Scientist runs multiple times a year, so I’d recommend it for anyone interested in outreach and science communication, as what is the point of doing the work we do if we can’t explain it to school children?

Matt

ISTM Translate blog post COMPETITION!

To all ISTM young researchers and students...

We are keen to encourage more of our young researchers and students to engage with our ISTM Translate blog and are keen for you to play a bigger role in writing and editing articles for it. The blog has global reach with well over 5000 views to date and regular visitors from across 10 different countries. As well as having the opportunity to promote the Institute on an international level and to communicate stories and information that are of interest to you to a wider audience, you also have the chance to hone your lay-writing skills.

As you may have already heard, Keele University is now a member of The Conversation. The Conversation is an independent source of news and views, sourced from the academic and research community and delivered direct to the public. Their team of professional editors work with researchers to unlock their knowledge for use by the wider public.

So with a view to improving your lay-writing skills and helping ISTM to play a greater role in the public dissemination of research, we have decided to hold a competition to which you are all invited to participate.

Please see the information below from Dr Dimitra Blana, who will be helping to facilitate this writing competition...

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You are invited to submit a post to the ISTM Translate blog describing a research topic of your choice to the general public.

Why, you ask? Because it will help you improve your public engagement skills, which is increasingly important for scientists. If that's not enough, there is also a prize, so read on!

Your blog post should be a lay-term summary of either a research paper you recently published, or the scientific area you are investigating. It should be no more than 1000 words and include some compelling images.

Submit your blog post and images to me over email (d.blana@keele.ac.uk) by 30th June to be entered into a competition to win a cash prize.  First prize is £100 and the Runner Up prize is £50! The winners will be announced during a lunch party in the Guy Hilton Research Centre on Thursday 21st July.

A few points to consider when preparing your post:

• Make sure the language is appropriate for the general public. To ensure that everyone can understand your writing, it will be judged by people outside your research area. I am thinking of enlisting my 14 year old Greek cousin.
• Journal paper writing rules do not apply: be natural and informal. Of course make sure that the science is sound!
• 1000 words is the upper limit, but try to keep it short and engaging. Can you keep my 14 year old Greek cousin's interest for 1000 words? Or will she switch to cat videos half way through?
• Use images you have permission to use. And remember that journal paper result figures are not usually considered compelling by the general public.

Best wishes
Dimitra

Successful Guy Hilton Research Centre Open Afternoon

Dr Paul Roach (Left) and Dr Ed Chadwick (Right) introduce themselves.

Last week, ISTM held a successful open afternoon for people interested in studying a post-graduate degree in Medical Engineering. The Open afternoon attracted a good intake of participants from a range of different backgrounds. The participants were able to learn about the School of Medicine's MSc courses in Biomedical Engineering and Cell and Tissue Engineering, and learnt about the cutting edge research being carried out by the Institute for Science and Technology in Medicine. They also had the chance to see state of the art laboratories and talk to current and former students and researchers.

Dr Ed Chadwick, who organised the event along with Dr Paul Roach, said "We were delighted to see such strong interest in our research and the courses we offer from the Keele undergraduate community and those from the wider region that were able to join us.  People often have a fairly vague idea of what medical engineering comprises, and it was really nice to see that they were genuinely interested and indeed excited by what we do. The people who work in the area are typically from really diverse academic backgrounds, and this was reflected in the people attending. The day was definitely a success with really strong interest, and we look forward to doing it again!"