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Bio-Sensing Technology Series: Microbial detection and biocontrol 

Posted by Denise Hope | 0 comments
Welcome to the third article in our Bio-Sensing Technology series, looking at microbial detection and biocontrol. This technology is led by Dr Darren Reynolds and we ask him to tell us a bit more about his research.

So what is microbial detection and biocontrol? What are the benefits and applications?
Microbial Detection and Biocontrol methods can be developed to ensure effective safeguarding of human health within environmental, healthcare and agri-food processes. Microbial detection and biocontrol technology platforms have been developed for a range of industrial and biomedical applications in collaboration with academia, business and enterprise.

Applied microbiological modelling and bio-photonics techniques (including low-light imaging, hyperspectral imaging and spectro-fluorometry) are used for the quantitative analysis and spectroscopic interrogation of biological processes.

Can you give us some examples of projects where the paramagnetic particle-based detection system has been used?

Electrochemically activated solutions (ECAS)
Due to the limitations associated with the use of existing biocidal agents, there is a need to explore new methods of decontamination to help maintain effective bioburden control, especially within the healthcare environment. ECAS have been shown to have broad spectrum antimicrobial activity and have the potential to be widely adopted due to low cost raw material requirements, ease of production and biocompatibility. The institute has expertise in the development and deployment of these novel biocides, including research undertaken in biodefence, biocontrol and food quality and safety.

Water quality sensors
In collaboration with industry, cutting edge deployable optical sensors for water quality monitoring based on fluorescence spectroscopy are being developed. These sensors can be deployed and left in situ for extended periods enabling online real-time water quality monitoring.

Bacteriophage (viruses that infect bacteria)
Bacteriophages are perhaps the most predominant biological entities in the biosphere and have great potential as antimicrobial agents within clinical and industrial settings. Real-time detection technologies based on bioluminescent bacterial reporters are utilised to screen for and determine the efficacy of, newly discovered bacteriophages for use within clinical, food safety and agricultural applications.

Non-thermal plasma
Non-thermal plasma is generated by electric discharge excitation producing a neutral ionised gas. This novel technology has known antimicrobial properties and is being evaluated in collaboration with industrial partners for various decontamination applications.

Lead researchers: Dr Darren Reynolds, University of the West of England

For more information about Microbial Detection and Biocontrol, please visit the Centre for Research in Biosciences website.

Bio-Sensing Technology Series: Paramagnetic particle-based detection system 

Posted by Denise Hope | 5 comments
Welcome to the second article in our Bio-Sensing Technology series, looking at a paramagnetic particle-based detection system. This technology is led by Professor Richard Luxton and Profesor Janice Kiely, directors of the Institute of Bio-Sensing Technology (IBST), and we ask them to tell us a bit more about their research.

So what is a paramagnetic particle-based detection system?
The paramagnetic particle-based detection system uses paramagnetic particles (PMPs) to detect biological interactions between two complementary binding partners such as antibodies and antigens (analytes) in an immunoassay.

This is a biosensor that can provide measurement of analyte concentration within a test sample in just few minutes. In this system, the test samples and PMP labels are added to a reaction vessel in the biosensor and are attracted to a reaction surface at the base of the vessel, using a magnet where specific binding takes place. Unlike other immunoassay systems no extra washing or processing procedures are required. The bound particles, and associated antigen are detected using a coil under the surface of the biosensor.

What are the benefits?
The use of paramagnetic particles as a label in an immunoassay has resulted in the development of a rapid and highly sensitive biosensing device. Substances in the part-per-trillion concentration range have been measured. The novel instrumentation is inexpensive and can be powered by standard, small batteries to be used as a handheld system for field testing.

What are the applications of the paramagnetic particle-based detection system?
This is a platform technology and has a wide range of applications in areas such as point of care diagnostics, environmental testing, bio-security and food quality.

Can you give us some examples of projects where the paramagnetic particle-based detection system has been used?
A number of projects have been funded to develop the technology for different applications to meet specific needs for companies. For example:

Diagnostic markers: Includes a range of projects to detect biomarkers of disease such as cardiac or cancer markers. There is also a project for the raid detection of bacteria such as clostridium difficile.

Environmental testing: Government funded projects, for explosive residue in the environment enable a highly sensitive and rapid assay to be developed. 

Food safety and quality: A number of projects in this sector have focused on the rapid detection of bacteria in food materials.

Lead researchers: Professor Richard Luxton and Profesor Janice Kiely

For more information about the paramagnetic particle-based detection system, please visit the Institute of Bio-Sensing Technology website.

Bio-Sensing Technology Series: Microbial Fuel Cells 

Posted by Denise Hope | 1 comment
Ioannis IeropoulosWelcome to the first of our Bio-Sensing Technology series, looking at Microbial Fuel Cells. This technology is led by Dr Ioannis Ieropoulos, a Senior Research Fellow in the Bristol Robotics Laboratory (BRL) and we ask him to tell us a bit more about his research.

So what is Microbial Fuel Cell technology?
Microbial fuel cells employ live bacteria to produce electricity by breaking down organic matter. The technology commonly consists of two halfcells – an anode and a cathode – that are separated by an ion selective membrane. Commonly bacteria are in the anode side, and chemicals or oxygen are in the cathode side, which complete the reactions (ie close the circuit) to generate power.

What are the applications of MFC?
This technology looks at utilising a wide range of organic compounds that are considered to be waste, for creating energy. The MFC technology may have potential in a domestic or village setting for the micro-generation of energy.

Applications primarily include Autonomous Robotics, stand-alone Remote Sensing, Waste and Wastewater treatment and utilisation. Further developments may include the powering of other specialized off-the-grid equipment such as portable IT systems, Environmental Monitoring tools and Medical Support apparatus.

Can you give us some examples of projects where MFC has been used?
The MFCs technology has already been used to generate power for autonomous robots, such as EcoBot-I (powered by sugar), EcoBot-II (powered by flies and rotten fruit diet) and EcoBot- III (powered by wastewater).

What are you working on at the moment?
The latest project, ‘Urine-tricity: electricity from urine',  aims to produce electricity from urine through stacks of small-scale microbial fuel cells whilst at the same time cleaning the urine stream and getting rid of pathogens that may be found in urine. The project, if successful, has the potential to achieve energy recovery from urine and other waste streams, and produce a cleaner effluent, which is dischargeable into the environment without expensive wastewater treatment in developing world countries.  

Lead researcher: Dr Ioannis Ieropoulos

For more information about Microbial fuel cells, please visit the Bristol Robotics Laboratory website.

Understanding chronic pain: an interview with Professor Candy McCabe 

Posted by Kathleen Steeden | 13 comments

It’s hard for most of us to imagine living with pain that doesn’t have a physical explanation. For medical professionals it can present a massive challenge: how can you diagnose a condition or advise treatment for a patient suffering from persistent pain with no obvious cause? Professor Candy McCabe is a UWE researcher and Consultant Nurse at the Royal National Hospital for Rheumatic Diseases, Bath, who is working to understand these chronic pain conditions and develop therapies to provide relief to sufferers.

Prof Candy McCabeProfessor McCabe’s research is supported by an NIHR (National Institute for Health Research) Career Development Fellowship for five years, which will fund a series of projects focused on understanding the roles of the motor and sensory systems in the perpetuation, exacerbation and relief of chronic pain. I met with her to discuss her research ahead of her inaugural lecture at UWE in April.

How did you become interested in researching pain?
I have worked at the Royal National Hospital since ’96 and am still based there two days a week. I started as a research nurse in Rheumatology and conducted my MSc exploring pain in rheumatoid arthritis where patients had perceived joint swelling but no physical sign of it. The ‘phantom swelling’ we found in this population led me into the phantom limb literature and I started to look at those with Complex Regional Pain Syndrome. We started a research clinic in 2000 and I began my PhD in 2001. The research clinic grew into a national service for patients with CRPS and is now the leading UK centre for this condition.

What did your PhD research focus on?
It focused on complex regional pain syndrome [CRPS], which is a condition that causes severe, continuous pain, usually affecting an arm or a leg. For example right after a minor fracture a sufferer might almost immediately start to complain that the limb hurts far more than would be expected for the injury sustained. If they have a plaster cast it’s quite common for sufferers to complain that it’s too tight even if the medical professional thinks that it’s fitted correctly. The limb sometimes appears hot and sweaty, perhaps with changes of colour or skin texture, the hair might have grown very thick and the nails unusually quickly. Approximately 80% of people with these symptoms will just recover, but there’s that small percentage of people who develop chronic problems so it’s important that this is diagnosed early.

It sounds really scary…
It’s a source of extreme stress. People complain that they feel that their arm is a completely different size and shape, or that there are parts missing. Some patients even say that they want to cut off their own arm, they hate it so much.

Are these patients often dismissed by their GPs?
Actually, often their GPs are their biggest champions but they are frequently dismissed after being referred to a number of specialists for x-rays and MRIs which come back with normal results.

What testing methods did you use to understand the research participants’ symptoms if there were limited physical signifiers?
We started by collecting detailed clinical descriptions of their pain. We quite often looked at the literature about other complaints in order to understand the mechanisms at work. Some of the descriptions were very similar to rheumatoid arthritis and phantom limb pain (a condition where an amputee continues to feel sensations or pain in their missing limb).

During my PhD research I found that when you touched the painful limb of someone with CRPS they could sometimes feel the same sensation in other areas of their body. For example, if you touched their painful hand they would feel exactly the same sensation on their face, even though this area was not painful. Amputees had also exhibited some of these symptoms. These misplaced feelings are called referred sensations and they are a clinical representation of the changes that take place within the sensory maps in the brain. There are similar changes that occur in the motor maps and my research has been focused on gaining a better understanding of how these changes in sensory input and motor planning, may relate to pain.

What treatment options did you start to look at to resolve this ‘cross-wiring’ problem?
We looked at mirror visual feedback that had been shown to help relieve phantom limb pain. A person sits either side of a mirror with their unaffected limb reflected, and exercises both limbs together, viewing the reflection of the healthy limb in the mirror. This illusion gives the patient an image of a normal, unaffected limb in the felt position of their actual affected limb. So we provide corrective sensory feedback.

Did it work?
It did work remarkably well; especially for patients displaying early symptoms. We also tested whether we could trigger pain and other sensory changes in healthy subjects using mirrors by generating a mismatch between sensory input and motor output. We positioned subjects with their limbs either side of a mirror and they moved their arms in different direction whilst looking at the reflection that showed them moving in the same direction. This generated all kinds of changes in the limb hidden behind the mirror, even after just 20 seconds. Some subjects perceived altered weight and temperature of the limb. For some people they felt they had ‘amputated’  the limb they couldn’t see and others felt that they had an extra arm. In a small percentage of people it also caused pins and needles or an unpleasant sensation that was strong enough that they didn’t want to continue with the study.

Did your research reveal anything about who is more likely to be affected?
We found that some people were particularly vulnerable to this and others were very tolerant. It does suggest that some people are predisposed to these conditions. We were interested to see if people with other chronic pain conditions may also perform poorly on this task. Fibromyalgia is another chronic illness that can cause pain and clumsiness and poor body perception. It’s thought that fibromyalgia might also be caused by an underlying motor/sensory discrepancy and as we predicted these patients did worse on the mismatching mirror test.

It sounds like many of these painful conditions are related?
CRPS is the model condtion we have used to explore chronic pain but the mechanisms are the same for a number of other conditions that present as persistent neuropathic pain. They can affect any part of the body and people have experienced identical symptoms in the face, the back, even the internal organs such as the bladder.

Does that mean that treatment options are the same? What are the new treatment options you are developing?
The new therapies we have been developing for CRPS are informed from what we know about other pain conditions. These new therapies include mirror visual feedback, electrical sensory discrimination—where you pass stimulus through four pairs of electrodes placed on the affected part of the body and the patient has to focus on the sensory information to identify which pair it being stimulated, and motor planning using imagined movements.

Is there more support available for CRPS sufferers now than when you started your research?
We have established a national specialist network for research/health professionals and a CRPS-UK register, which is run for us by the University of Southampton. This Network and Register help us to conduct multi-centre studies into CRPS and follow cohorts of patients over time. We are just starting to conduct these studies with our European collaborators and this will help greatly with larger clinical studies. We also provide training for health professionals, helping them to identify CRPS early on in the condition and consider novel treatment methods.

I imagine it could be quite distressing to work with people who live in constant unexplained pain. Do you have good feedback from patients and research subjects?
Oh yes, we do get excellent feedback. From a service perspective our patients love that there’s a group of people who understand them, who don’t try to touch their limb, which is the impulse of most healthcare workers trying to diagnose pain. And we will directly ask questions such as whether they feel like they want to cut off the limb. Patients are often very distressed by these feelings but frightened of telling healthcare professionals about it as they fear they will be thought of as mad.

It must be such a challenge for others to understand how it feels to suffer with CRPS?
Yes and I’m working with Dr Ailie Turton (Department of Nursing and Midwifery), Professor Nichola Rumsey (Centre for Appearance Research), Dr Mark Palmer (Department of Computer Sciences and Creative Technologies), and Dr Jenny Lewis (from the Royal National Hospital for Rheumatic Diseases), on a project that could help. Mark has helped us to develop software that uses an avatar of a person that can be manipulated by a CRPS sufferer to visually depict what their limb feels like to them. They can make all sorts of changes—changes in size, colour, texture, they can even visually represent the temperature of their limb.

An example of the avatar developed as part of the HEAT funded project 'Development and evaluation of a tool for assessing body image'. A sufferer of Complex Regional Pain Syndrome can manipulate the image to show changes in the feelings of the size, temperature, skin texture, etc of their affected limb.

It must be comforting for patients that somebody is willing to listen and accept their symptoms?
And quite often that is the most therapeutic thing for people I think; just for someone to listen to them, to believe them, and to offer an explanation for the way they’re feeling.

For more information contact Professor Candy McCabe

Bioluminescent bacteria: An interview with Professor Vyv Salisbury 

Posted by Kathleen Steeden | 6 comments

Prof Vyv Salisbury is a microbiologist from the Department of Applied Sciences involved in applied research with bioluminescent bacterial biosensors. In 2003 Vyv obtained Wellcome Trust Engaging Science funding to put on an exhibition in the @Bristol Science Centre titled ‘Lighting up biomedical research’ with bioluminescent bacteria and flashlight fish. In 2009 she became involved with a UN backed project to evaluate medical uses of Himalayan oregano oil which gave her an opportunity to camp up at 3000m in the Himalayas whilst visiting the herb picking cooperative in the Himachal Pradesh. I met up with her to discuss her work ahead of her professorial inaugural lecture at UWE on 16 December.

You have your inaugural lecture coming up and the title is ‘Many bugs make light work: A personal journey with bioluminescent bacteria’. How long have you been researching with bioluminescent bacteria?
Since 1999.

So relatively recently in your career?
Yes, the use of genetically modified bioluminescent bacteria in microbiology research is a comparatively recent development. There were originally only a few groups worldwide researching the applications;  it’s just great that it’s taken off as it has. It’s such a useful tool.

What are the key projects you’re working on at the moment then?
At the moment bioluminescent bacteria have enormous potential as a marker to see how well cancer chemotherapy works so that’s very exciting.

What interests you the most about working with bioluminescent bacteria?
That’s easy. As a microbiologist you become used to working with bacteria that you can’t see. With bioluminescent bacteria you have a visible marker that tells you where the bacteria are and whether they’re metabolising. Other traditional methods, such as putting the bacteria into a growth medium and seeing whether they grow, are much more indirect.

So there’s an immediacy about it?
Exactly. With growth cultures you won’t have your results for 24 hours or so. With bioluminescent bacteria it’s almost instant. The other great benefit is that you can use them in-situ. I can give you an example: if we are using bioluminescent bacteria to test the presence of salmonella on a piece of meat as it’s being heated, we can see the results more or less instantly – as the salmonella is killed it will stop glowing. You can see the results with less manipulation. Previously we would have had to stop to test for the presence of bacteria at each stage by grinding up a bit of the meat and seeing whether we could culture bacteria from it.

Recently on the blog we featured a video of glowing bacteria from Dr Gareth Robinson’s work. Do you work with him and Dr Darren Reynolds? Are there others in the Faculty researching using bioluminescent bacteria?
Oh yes of course. I work with Darren and Gareth and was director of studies for Gareth’s PhD. Professor John Greenman uses bioluminescent bacteria to investigate biofilms, as does Dr Shona Nelson. Shona also uses bioluminescent bacteria to test the efficacy of probiotic bacteria, and looking at bacteria that stay alive inside protozoa.

So there’s a lot of interest in bioluminescent bacteria within the Faculty of Health and Life Sciences?
Oh yes and it’s great. As more researchers have become interested in it and we have been able to publish our results, we’ve been able to apply for more research funding and use it to buy equipment. Subsequently we’ve really built up our facilities for this research and now have state of the art technology including low light imaging cameras.

In 2009 you became involved with a UN backed project to evaluate the medical uses of Himalayan oregano oil and visited the Himalayas. How did you become involved in the project and what are the aims?
I was approached by a colleague working in India who had established Biolaya Organics to cultivate Himalayan herbs and generate sustainable employment for local people. He needed to be able to test how well the oregano oil killed bacteria and wanted to know whether we could use bioluminescent bacteria to test its effectiveness as a disinfectant. Our research so far shows that it is really effective, even when used as a vapour.

The research is funded by the UN and is interesting from a sustainability point of view as well as a scientific one. Before the local people were gathering the roots of rare mountain herbs that wouldn’t grow back and it was only just make them enough money to live. However, oregano can be picked like tea and the plant will continue to grow, which provides ongoing employment for locals and protects other indigenous herbs.

And have you been able to visit India and see the project in action?
Yes, my first trip was to a workshop in Delhi for three or four days, where I had to present a paper, but on the second trip I actually had the opportunity to stay in the Himalayas and visit the oregano fields , which was absolutely incredible.

Thanks Vyv. Looking forward to the lecture!

Prof Salisbury in the Himalayas

Professor Salisbury at her camp in the Himalayas.

Click here for more information about Professor Salisbury’s inaugural lecture
Click here to see a video of bioluminescent bacteria