Research Activities
A wide range of multidisciplinary translational research is carried out by researchers and clinicians within the Essex Biomedical Sciences Institute. Our research focuses on three overlapping themes. Click on the theme title to read about current research projects within that theme:
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Wellbeing and Healthy Lifestyles
Exercise and health; childhood fitness and obesity; cardiac health; physical activity and the environment (green exercise) -
Ageing
Interventions for age-related conditions and diseases; human-centred robotics for assisted living -
Disease
Heart and vascular disease; infectious disease; cancer; dementia; autoimmune disease; developing artificial blood
Research is supported by state-of-the-art facilities in The School of Biological Scienceswithin the centrally managed Infrastructure Spine. Recent investment has provided modern facilities for imaging biological systems, transcriptomics, proteomics and bioinformatics.
Our research activities have been supported by a variety of sponsors: MRC, BBSRC, EPSRC, ESRC, EU, NHS, Wellcome Trust, Cancer Research UK, National Institute of Health, Heal Cancer Charity, Breast Cancer Campaign, Royal Society, EMF Biological Research Trust, GlaxoSmithKline, Heart Research UK, Alzheimer’s Research Trust, Help the Aged, Parkinson's Society.
Wellbeing and Healthy Lifestyles
East of England Healthy Hearts Study (Dr Gavin Sandercock)
The East of England Healthy Hearts Study is one of the
largest paediatric health studies in the UK. To date over 8000 children from
Essex and Suffolk have been assessed for fitness, body composition, blood
pressure and physical activity levels. Studies published so far show worrying
declines in children's fitness (Sandercock
et al 2010). We have demonstrated that children's fitness can be
tested with good validity in the school setting (Voss
and Sandercock 2009). We have also published contemporary normative
data for, cardiorespiratory fitness (Sandercock
et al 2008), muscle power (Taylor
et al. 2010) and muscle strength (Cohen
et al. 2010) and shown that fitness is related to the way children
travel to school; cyclists are the fittest (Voss
et al. 2010). We have recently shown that children who eat breakfast
are fitter and more active than those who do not (Sandercock
et al. 2010). The study's findings have been covered in a number of
television reports, by the
American College of Sports Medicine, in
newspaper articles and was even cited in the UK
Chief Medical Officer’s
annual report 2009.
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Metabolic Demands and Gait Patterns of Shuttle vs. Treadmill Walking Test within Cardiac Rehabilitation Patients
(D. Taylor A. Osailan, G. Sandercock, M. Taylor, T. Cudmore, R. Beneke)
In patients undergoing cardiac rehabilitation, shuttle walking (natural walking
on ground with turns after every 10 m) and/or treadmill walking (walking on a
moving surface without turning) tests are used to test functional capacity in
exercise prescription. However, whether shuttle walking and treadmill walking
result in similar metabolic demand and/or gait patterns is not known. We
compared metabolic demand based on respiratory and blood lactate measurements as
well as gait patterns based on kinematic measurements in clinically stable
cardiac rehabilitation patients. We found that metabolic demand and gait
patterns were similar at the most biomechanically economical walking speeds
between 1.17 and 1.67 m•s-1. Up to velocities of 1 m•s-1 treadmill walking was
more metabolically and biomechanically demanding than shuttle walking whilst the
opposite was observed at and above velocities of 1.83 m s-1. We conclude that
shuttle and treadmill walking test results cannot be used interchangingly.
Particularly, the functional capacity of more heavily impaired cardiac patients
may be underestimated if tested on the treadmill without metabolic measurements.
This work was carried out by a research team from the Health, Exercise and Active Life Research Unit, the Human Performance Unit and the Phoenix Club (centre for cardiac rehabilitation).
Using the Nintendo Wii to improve balance and quality-of-life in recurrent elderly fallers
(Dr. M. Taylor, Dr. M. Griffin, Dr T. Shawis, Ms R. Impson)
The consequence of falling can be
physically and psychologically debilitating - even resulting in death. The cost
of falls is approximately £5 million per annum in North Essex. For the UK, falls
are reported to cost the NHS £980 million. We are undertaking an evaluation of
the use of the Nintendo Wii-Fit™ as a potential adjunct to standard NHS falls
training. This is a novel approach for balance rehabilitation for those elderly patients
who are repeat fallers. Anecdotally the Wii-Fit™ is being used in a number of
settings within the NHS and Veteran Associations in the US but there is a
paucity of evaluative research for the Wii-Fit™ as rehabilitation tool such as
we are proposing. The Wii-Fit™ is already being used, in a limited fashion by
Colchester Hospital (CHUFT) falls prevention exercise group and feedback from
both patients and physiotherapy staff has been positive. We therefore plan to
carry out a small random control trial comprising 60 patients, using pre and
post intervention measures (biomechanical, psychological and functional) to
evaluate the utility of the Wii-Fit as a rehabilitation tool.
Falls is a multi-factorial issue, thus this project brings together a range of expertise. The clinical team from CHUFT comprises of a consultant physician (care of the elderly, Dr Teshk Shawis) and a clinical specialist physiotherapist (care of the elderly, Ms Rebecca Impson). The academic team from the University of Essex comprises of a biomechanist (Dr Matthew Taylor), a psychologist (Dr Murray Griffin) and a research officer (Mr Darren McCormick).
Biomarkers of Breast Cancer (Professor Elena Klenova)
Breast cancer is one of the most common
diseases in the Western world. Great efforts to find the means to detect and
monitor breast cancer have been made in recent years. One of the most promising
developments involves identification of cancer biomarkers. Biomarkers are
molecules that are associated with the disease: they can be measured in body
fluids and tissues and serve as valuable indicators and tools for diagnosing
cancer and monitoring the outcome of treatment. We discovered that a protein
called BORIS, which was found in blood cells of breast cancer patients, has a
good potential to be an early biomarker of breast cancer and as a biomarker to
monitor the efficacy of pre-operative chemotherapy. In collaboration with the
clinicians we are now evaluating these findings and hope to apply them in clinical practice in the future. The presence of BORIS
in blood cells from a breast cancer patient can be seen in the illustration –
cells containing brown colour are cells with BORIS (indicated by arrows).
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Identification and validation of new biomarkers in colorectal cancer (Dr. Nikhil Pawa, Mr Tan Arulampalam, Professor Elena Klenova)
Colorectal
cancer is the third most common cancer after breast and lung, with around 106
new cases diagnosed each day in the UK. Survival rates exceed 90% if the disease
is detected at an early stage. The colorectal cancer screening programme in the
UK is a faecal based test with varying compliance and considerable false
positives. There is a great need to develop an alternative test based on the
identification of specific biomarkers for both diagnosis and treatment
monitoring. This study aims to validate the role of a specific protein BORIS as
a potential biomarker for colorectal cancer. Expression of BORIS will be
analysed both in the blood and tissue of patients with colorectal cancer and
correlated with their clinical cancer staging. Furthermore patients will also be
followed after resectional cancer surgery to identify changes in the expression
of BORIS within their blood. Further 2 dimensional gel electrophoresis is also
planned to search for alternative biomarkers within the leukocytes of patients
(The image is Immunocytochemistry showing good expression of BORIS in the
leukocytes of a colorectal cancer patient).
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The role of Acanthamoeba in human urinary tract infections (Dr. Selwa Alsam, Mr. Gerald Rix, Dr. Tony Elston)
One
of the most common hospital acquired infections is urinary tract infection (UTI).
A major factor contributing to the prevalence of UTI is the widespread use of
urinary catheters. Within the general community there are currently many
post-operative patients with long-term experience of using catheters, some of
whom will require further hospitalisation and as a consequence suffer
re-infection, particularly female patients. Because microorganisms isolated from
urinary catheters tend to be more resistant to antibiotics and they form
biofilms on the surface of these devices, remedial treatment is problematic.
Moreover, it has been established that the formation of a bacterial biofilm
greatly encourages the survival of free-living amoeba, such as Acanthamoeba. The
ability of Acanthamoeba to feed on Gram-negative bacteria as well as to harbour
potential pathogens, notably Legionella pneumophila, etc., suggests that amoebae
and bacteria engage in a complex interaction, which may play a significant role
in human health issues. Not least, under adverse conditions, Acanthamoeba
transform into a highly resilient cystic form, which does not appear to
disadvantage the internalized bacterial endosymbiont. It is our intention to
collect the urinary catheters from patients with UTI, bladder cancer and
diabetic patients (insulin-dependent and insulin-independent) and to test for
the presence of Acanthamoeba and their cysts. We will also investigate the
survival rate of Acanthamoeba in urine samples taken from the aforementioned
patients and compare them with urine samples obtained from healthy adults and
children under 5 years.
Dr. Selwa Alsam from the School of Biological Sciences, University of Essex, is collaborating on this project with clinicians Mr. Gerald Rix and Dr. Tony Elston from Colchester Hospital.
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Artificial blood: reducing the intrinsic toxicity of haemoglobin (Professor Chris Cooper)
Developing alternatives to blood transfusions would have important clinical benefits. Blood needs to be typed, cannot be guaranteed virus-free and has a short shelf life. The dream of a long-life, pathogen free blood supply has been a holy grail for biotechnology for over two decades. However, previous blood substitutes have failed in clinical trials, due to the intrinsic toxicity of the haemoglobin molecules used. Under conditions of oxidative stress, haemoglobin forms a highly reactive oxidative species: a ferryl, Fe(IV,) iron. This will initiate lipid peroxidation with consequent production of toxic vasoconstrictor molecules and apoptotic precursors. We have shown that genetically modifying (adding/removing) specific tyrosine residues on haemoglobin (see Figure 1) allows us to control the reactivity of this ferryl haem. Two patents have been filed exemplifying different effects on ferryl reactivity. We are using in vitro and cell assays to demonstrate which class of mutants has the most favourable effect on the intrinsic toxicity of haemoglobin. This information will provide the technical proof of concept for the next generation of blood substitutes.
The Essex project has featured extensively in the media including national TV news bulletins in the UK (Channel 4 News), Rumania (TVR1, TVR2) and Greece (ERT) and national radio features on BBC Radio 4 (Material World).
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Figure 1 Key aromatic amino acids in haemoglobin alpha subunit (left), beta subunit (centre) and myoglobin (right) |
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Bacterial resistance to host defence (Professor Chris Cooper)
Professor Cooper's research team is looking at how bacteria can evade the host defence systems. Working with colleagues from the University of Sheffield (Professor Robert Poole), they have discovered how an enzyme mechanism helps Escherichia coli (E. coli) bacteria to resist attack. E. coli, which causes a number of serious diseases, gets its energy from enzymes that react with oxygen. One of these, called cytochrome bd, is crucial for virulence. Prof. Cooper’s group studied the interaction between cytochrome bd and nitric oxide gas. Nitric oxide, the toxic by-product of car exhausts, was originally thought only to interact with mammals as an environmental pollutant. It is now known that all mammalian cells produce this gas. At low doses it is used as a signalling molecule, increasing blood flow and blood volume, at high doses the body’s immune system uses nitric oxide to attack invading bacteria. Prof Cooper’s team discovered, in contrast to the alternate cytochrome bo enzyme, the cytochrome bd enzyme was able to prevent nitric oxide attack; this allowed the cells to survive longer. The enzyme’s resistance relates to its ability to induce a very fast dissociation rate for nitric oxide, allowing its replacement by the oxygen required for bacterial growth. E. coli cytochrome bd levels increase when the host white blood cells attack bacteria with nitric oxide. This study suggests why this adaptation evolved; it could have general implications for bacterial resistance to host attack. E. coli causes a long list of serious diseases including dysentery, diarrhoea, bladder infections and kidney failure, understanding how it resists attack by the host’s immune system is an important discovery. No protein resembling cytochrome bd exists in the human body. Therefore future research might be able to target cytochrome bd with specific drugs and kill invading bacteria, whilst not harming the human patient.
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Figure 1 Nitric oxide effects on different bacterial oxidases |
