MRes Medical Research DirectoryDire… · drugs on the luminal gastrointestinal tract. The current...

MRes Medical Research Directory

2020/21

Research Directory | Norwich Medical School | University of East Anglia of 60

CONTENTS

GASTROENTEROLOGY, GUT BIOLOGY AND MICROBIOLOGY PAGE 3

NUTRITION PAGE 18

DIABETES AND ENDOCRINOLOGY PAGE 24

MUSCULOSKELETAL BIOLOGY AND SURGICAL ANATOMY PAGE 28

ONCOLOGY AND HAEMATOLOGY PAGE 34

CARDIOVASCULAR RESEARCH PAGE 41

RESPIRATORY MEDICINE, RHINOLOGY AND EAR, NOSE AND THROAT PAGE 45

MENTAL HEALTH AND DEMENTIA PAGE 49

POPULATION HEALTH, PRIMARY CARE AND HEALTH CARE DELIVERY PAGE 53


Gastroenterology, Gut Biology & Microbiology


Gastroenterology, Gut Biology & Microbiology

RESEARCH AREA OVERVIEW

Gastroenterology research in Norwich offers a broad portfolio of research covering clinical research with

patients, laboratory and epidemiological research. Norwich Medical School is one of the UK’s major centres

for gastrointestinal research; senior academics in the School and the consultants at NNUH work in close

collaboration with other Institutes based at Norwich Research Park, including the Genome Analysis Centre,

the John Innes Centre and the recently established Quadram Institute (QI). Clinical gastroenterology

research is concentrated at the Quadram, which houses the NNUH Endoscopy Facility and provides research

facilities for academic scientists working on the biology of the gastrointestinal tract, alongside clinicians and

clinician-scientists in NNUH Gastroenterology. We also have strong contacts with major epidemiological

databases in the UK and USA to study dietary risk factors for gastrointestinal disease. This gives an excellent

teaching environment for research training.

Relevant Links http://www.uea.ac.uk/medicine/research/research-areas/gastroenterology-and-gut-biology

https://quadram.ac.uk/research_areas/gut-microbes-health/ Current Research Opportunities

Dietary risk factors for gastrointestinal disease – Prof Andrew Hart

Cardiovascular and gut health – Prof Alastair Forbes

Primary sclerosing cholangitis of the liver – Dr Simon Rushbrook

Gastrointestinal pharmacology, therapeutics and education – Dr Ian Beales

Gut microbes in health and disease – Prof Simon Carding

Gut microbes and disease (NHS primary and community care) – Prof Simon Carding

Autophagy and Crohn’s disease – Prof Tom Wileman and Prof Ulrike Mayer

Gut immunology and the microbiota early in life – Dr

Lindsay Hall

Maintaining intestinal barrier function – Prof Alastair Watson

Generation of organoids from stem cells to study innate immune responses in the GI tract – Dr Penny Powell

Unravelling pathogen-host-microbiota interactions in the human gut – Dr Stephanie Schuller

Mucus-associated gut microbiota in health and disease – Prof. Nathalie Juge (Quadram Institute)

Discovering novel antibiotics to combat resistance – Prof Arasu Ganesan

Upper gastrointestinal surgery – Mr Bhaskar Kumar

Medical Microbiology

Molecular diagnosis of infectious disease – Dr Justin O’Grady

Antimicrobial resistance – Dr Mark Webber

Antibiotic resistance – Prof David Livermore

Genomic Microbiology – Prof John Wain

Evolution and spread of antibiotics resistance – Dr Benjamin Evans

Emerging infectious disease – Prof Paul Hunter

Tropical Medicine

Parasite virulence – Dr Kevin Tyler

Antimicrobials – Prof Dietmar Steverding

http://www.uea.ac.uk/medicine/research/research-areas/gastroenterology-and-gut-biology

https://quadram.ac.uk/research_areas/gut-microbes-health/


Dietary risk factors for gastrointestinal disease

The aim of my work is to firstly conduct epidemiological aetiological studies in to the causes of inflammatory bowel

diseases and cancers of the oesophagus and pancreas, to allow the development of public health interventions to

prevent these diseases.

Translational studies will be conducted, invariably clinical trials, to develop novel treatments for patients with these

conditions.

We work with large observational databases including the EPIC Study (European Prospective Investigation in to

Cancer) and The Clinical Practice Research Database (CPRD).

Inflammation is a valuable defence against infection but chronic inflammation resulting from the sustained

production of inflammatory cytokines can contribute too many acute and chronic human diseases. Interestingly,

long-chain n-3 polyunsaturated fatty acids (also called PUFAs or omega 3s) found in oily fish can decrease the

production of inflammatory cytokines, and are therefore potential anti-inflammatory compounds. In Crohn’s

disease and ulcerative colitis we have shown inverse associations between higher intakes of dietary n-3

polyunsaturated fatty acids and the development of both Crohn’s disease and ulcerative colitis. Diets high in these

nutrients will be assessed in relation to increasing the proportion of such patients responding to biological

therapies. In oesophageal cancer we have reported people prescribed a statin are at a reduced risk of

oesophageal adenocarcinoma and feasibility work is now progressing on their role as an adjunctive treatment in

cancer patients. In pancreatic cancer, we are using detailed dietary information from food diaries assessing dietary

antioxidants, meat and saturated fatty acids in its aetiology. We are investigating the potential role of metformin

as a treatment for patients with this invariably fatal malignancy. Members of the research team include junior

doctors (clinical lecturer and academic clinical fellow grades) and medical students.

Contact: [email protected]

Cardiovascular and Gut Health The research of Prof Forbes’ group has a strong clinical bias focussed mainly on intestinal and nutritional

problems, particularly in inflammatory bowel disease and intestinal failure. We are interested in the interface

between nutrition and intestinal inflammation, and exploring this has been a key task for recent PhD and MD(Res)

students. A role of lipids in Crohn's disease is widely accepted, but the nature of the relationship and its

mechanisms remain controversial. Three related phenomena are under investigation: the almost pathognomonic

“creeping fat” seen around inflamed segments of the intestine, the epidemiological association of some forms of

fat with disease incidence, and the differential impact of nutritional therapies of varying fat composition. The group

is performing original work on markers of intestinal integrity and of nutritional manipulation with particular interests

in citrulline and glucagon-like factor 2 analogues, as well as contributing to major national and international

collaborations. An important new direction comes with the foundation of the Nutrition Group of the UEA Health

and Care Partners which takes nutritional assessment and intervention into the wider community outside hospital

practice with an increasing engagement with non-medical researchers.


mailto:[email protected]



Primary sclerosing cholangitis of the liver Primary sclerosing cholangitis (PSC) is one of the archetypal

autoimmune liver diseases characterised by biliary

inflammation and fibrosis that can lead to both cirrhosis and

cholangiocarcinoma. A major focus of our work is to develop a

greater understanding of how these genetic loci are associated

with the development of PSC by studying the immune system

in both the liver and bowel of patients with PSC.

At present PSC is the 5th commonest indication for liver

transplantation in the UK. Although the exact pathogenesis

remains unclear, PSC is thought to have both environmental

and genetic causes, with 16 genetic

loci currently identified and further genetic loci undergoing

evaluation in an international GWAS meta-analysis of which I am a collaborator. Current projects include studies of the role played by genetic variation in PSC and analysis of dendritic cell and T-cell subsets in the pathogenesis of the disease. Contact: [email protected]

Gastrointestinal pharmacology, therapeutics and education Dr Beales has a wide portfolio of research interests

spanning clinical gastroenterology to education and

training. In general this focuses on mechanisms of

disease processes and in particular the interactions of

drugs on the luminal gastrointestinal tract. The current

research portfolio includes participation in several

international multicentre trials of novel biological and

small-molecule inhibitor agents as well as locally

delivered hypothesis-driven studies examining the

mechanisms of drug and hormone effects particularly

in Barrett’s oeosphagus and inflammatory bowel disease.

A variety of experimental approaches have been utilised included laboratory cell line studies,

immunohistochemistry (collaborating with colleagues in histopathology), case-control methodology, systematic

literature review and metaanalysis and interventional studies.

Recent important work has included the seminal original paper describing the mechanisms of the anti-cancer

effects of statins in oesophageal adenocarcinoma, subsequently followed with several case-control studies and a

systematic review confirming the clinical benefits. A detailed series of studies have illustrated the mechanisms

linking acid-reflux, obesity and oesophageal cancer: showing how leptin combined with acid to promote

oesophageal adenocarcinoma and how adiponectin may have inhibitor actions. Further studies to unravel these

effects are ongoing.

Other studies have explored the safety of cyclo-oxygenase inhibitors in patients with inflammatory bowel disease,

in particular showing the safety and efficacy of COX-2 inhibitors as well as the use of novel therapies to treat iron

Study or Subgroup

Nguyen 2010

Nguyen 2009

Kastelein 2011

Kantor 2012

Beales 2012a

Total (95% CI)

Heterogeneity: Chi² = 1.20, df = 4 (P = 0.88); I² = 0%

Test for overall effect: Z = 4.04 (P < 0.0001)

Weight

43.9%

9.5%

15.9%

11.5%

19.2%

100.0%

IV, Fixed, 95% CI

0.58 [0.38, 0.88]

0.73 [0.30, 1.78]

0.52 [0.26, 1.03]

0.71 [0.32, 1.59]

0.45 [0.24, 0.84]

0.57 [0.43, 0.75]

Odds Ratio Odds Ratio

IV, Fixed, 95% CI

0.2 0.5 1 2 5

Statins beneficial Statins hamful



deficiency anaemia and microscopic colitis. Educational projects have examined timing of endoscopy during the

day on colonoscopy performance, predictors of publication of abstracts presented at conferences and attitudes to

the use of probiotics.


Gut microbes in health and disease A major research focus of the group is to understand how microbes (bacteria and viruses) resident in the lower

human GI-tract (the microbiome) interact with their host to maintain lifelong health, and how microbial dysbiosis

can lead to chronic diseases affecting not only the GI-tract but elsewhere in the body, including the brain. Current

projects in the group include:

The Gut-Brain axis: Identify factors produced by gut microbes that impact on specialised intestinal epithelial cells of the enteric endocrine and nervous systems that can alter signalling in the CNS.

The role extracellular (outer membrane) microvesicles produced by gut bacteria play in mediating crosstalk between the intestinal microbiota and host cells.

The role of the intestinal virome and prokaryotic and eukaryotic viruses play in regulating bacterial populations and in promoting dysbiosis and chronic inflammation.

Development of novel bacteria-based therapies (e.g. probiotics, bacterial products and microbiota transplants) to treat and prevent intestinal inflammation.

Role of the microbiota in the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome.


Gut microbes and disease (NHS primary and community care)

Evidence is emerging that disturbances in the human gut microbiota can influence a number

of diseases including obesity, inflammatory bowel disease (IBD), myalgic

encephalomyelitis/chronic fatigue syndrome (ME/CSF), multiple sclerosis (MS), autism

spectrum disorder (ASD), Type 1 Diabetes, rheumatoid arthritis, food allergies and

gastrointestinal cancers and liver disease. This is an incredibly exciting time in science, when

technological advances in DNA sequencing, transcriptomics, proteomics and metabolomics

provide an unprecedented opportunity to explore not only the composition, but also the

function of the microbial communities that live in the intestinal tract of patients with these

diseases. The knowledge gained should provide new and important insights into disease

pathogenesis and innovative therapeutic modalities.

We are developing gut-related projects through collaboration with Norfolk and Suffolk primary

and community care, with contributions from secondary (NNUH) care, that are suitable for

students enrolled in UEA postgraduate degree clinical research masters courses (MSc

Clinical Research, MSc Clinical Research (CAT), MRes Clinical Science, MSc Health

Research, MSc Advanced Practitioner).

Obesity. Student research projects we are developing include the identification of the best and safest follow-

up care following discharge after bariatric surgery. Development of new dietary interventions for early

intervention in obesity, and analysis of behavioural and environmental factors that predispose to obesity.



http://www.sciencedirect.com/science/article/pii/S0140673607607508#gr4


Food allergy in children. Food protein-induced enterocolitis syndrome (FPIES) and food protein-induced

proctocolitis are non-IgE-mediated gastrointestinal allergies. FPIES causes changes in the intestinal

architecture in response to chronic exposure to a trigger such as milk. Avoiding milk results in normalization,

and its reintroduction results in a recurrence of partial villous atrophy. While this is similar to coeliac disease,

the two conditions differ in pathophysiology. Student projects will focus on literature reviews of the incidence,

presentation, likely mechanisms, diagnosis and management of FPIES accompanied by case histories of

patients in primary care diagnosed with FPIES and discussions with their families. A greater understanding

of the mechanisms may lead to development of diagnostic tests and management strategies for non-IgE-

mediated gastrointestinal allergies.

Gastrointestinal Symptoms in Adult Eczema Patients. Food allergy is a multisystem disease. Infants

present with a combination of symptoms predominantly in the skin, the gut and the respiratory system. Some

adult patients with food related atopic eczema and may also have gastrointestinal symptoms suggestive of

both IgE or non IgE mediated food allergy which can go unrecognised. Student projects will to look further

into the links between eczema and gastrointestinal symptoms in a cohort of adult patients. They will conduct

a literature review of bowel symptoms associated with adult eczema and non IgE mediated gastrointestinal

disease, and develop questionnaires for use in the dermatology clinic to identify gastrointestinal symptoms in

patients with atopic eczema. Students may also search the primary care database for adults with eczema

that have been referred with GI symptoms.

Gut microbes and mental health (neurodegenerative disease). By 2025 it has been estimated that there

will be more than 1 million patients in the UK suffering from dementia, more than 10% of which will be

attributed to East Anglia cases. Age-associated decline in mental health is associated with striking changes

in the make-up and activity of the intestinal microbiota with animal studies suggesting a direct causal link

between the production of toxic metabolites in the gut and brain pathology. The implications of altered host-

microbiome interactions in neurological disease would be far-reaching as they may underpin the development

of more effective therapeutic management of neurological diseases. Student projects will be to look further

into evidence for intestinal microbial dysbiosis contributing to chronic degenerative diseases such as dementia

and Alzheimer’s Disease through literature reviews and discussions with gut microbiologists at IFR and

dementia diagnosis and care experts within the NNUH and practitioners in primary and community care.


Autophagy and Crohn’s disease

Autophagy is a membrane trafficking pathway that generates

autophagosomes which deliver cytosol to lysosomes for

degradation. Autophagy provides a powerful means of removing

intracellular pathogens and is an important arm of innate

immunity to infection. Recent genome wide association screens

have identified autophagy gene Atg16L1 as a risk allele for

Crohn’s disease, an inflammatory disease of the bowel.

Susceptibility to Crohn’s disease is also linked to mutations in NOD2, a microbial sensor that activates autophagy

during infections. We are using mouse models to investigate whether the inflammation seen in Crohn’s disease is

caused by defects in the control of microorganisms by autophagy in gut epithelial cells.





Gut immunology and the microbiota early in life

Complex microbial communities (microbiota) colonise the body after birth. These beneficial bacteria shape immune defence, limiting infection by gut pathogens through a process of colonisation resistance. However, disturbances such as preterm delivery, caesarean sections and antibiotic exposure in early colonisation events can lead to increased susceptibility to pathogens, as well as allergic and chronic inflammatory diseases in later life. The Hall group work on building our knowledge of the contribution of specific bacterial species during early-life development, and how microbiota disturbances increase susceptibility to gut infection, focusing on Bifidobacterium. Current goals are:

To understand the effects of Bifidobacterium on critical colonisation resistance

Determine the short- and long-term impact of early life antibiotic-induced disturbances

Characterise and develop strategies for restoring a disturbed early-life microbiota to control gut infection, for use in infectious-disease settings.

Determine how a probiotic treatment strategy in at-risk preterm neonates alters the microbiota.


Maintaining intestinal barrier function

The Watson group have a long-standing interest in the regulation of cell death in

intestinal epithelial cells. Specifically, intestinal epithelial cell shedding, a special

form of cell death which leaves a “gap” in the epithelial barrier. Under normal

conditions the “gap” is short lived and barrier function is maintained at sites of cell

shedding. However, during inflammation cell shedding is increased, resulting in

loss of barrier integrity and creating sites for the potential entry of microorganisms

and luminal antigens. Importantly, increasing evidence predicts that certain

species within the gut microbiota (probiotics) can reduce intestinal inflammation.

On-going studies are focused on determining how the microbiota and probiotics

can regulate epithelial integrity and thus critical barrier function. Current projects

in the lab include:

Determining to what extent the microbiota plays in modulating the intestinal barrier

Characterise the host cell molecules involved in microbiota signalling and epithelial barrier integrity

Identification and development of probiotic therapies that would protection against chronic inflammation

The role of mucins in prevention of intestinal inflammation





Generation of organoids from stem cells to study innate immune responses in the GI tract

We are interested in the innate immune response in gut following viral infection which may explain the pathogenesis of human diseases. Innate immune responses to infection include apoptosis, autophagy and inflammation. When cells are infected with viruses these pathways are activated, the major pathway being production of interferon and interferon-stimulated genes (ISGs) triggered by dsRNA produced during viral replication. We are investigating this in primary cell cultures and gut organoids developed from small intestinal stem cells. In addition, we have used viruses to deliver exogenous genes to organoids to study innate immune pathways. The project will mainly involve bioimaging with confocal microscopy. Contact: [email protected]

Unravelling pathogen-host-microbiota interactions in the human gut

Research in our group is focussed on E. coli infections of the human gut leading to persistent diarrhoea (EAEC, EPEC), acute kidney failure (EHEC) and Crohn’s disease (AIEC). As bacterial pathogenesis in the intestine is largely influenced by host factors and the resident gut microbiota, it is important to apply biologically relevant model systems to decipher these interactions. To this aim, we are using advanced human cell- and tissue-based models (in vitro organ culture, stem cell-derived organoids, microaerobic diffusion chamber) which mimic the environment in the human gut. A better understanding of E. coli-host-microbiota interactions will contribute to the development of efficient antimicrobial- and probiotic-based therapies and facilitate identification of susceptible individuals.





Mucus-associated gut microbiota in health and

disease

The mucus-associated microbiota plays a predominant role in human health. We are studying how bacteria interact

with mucins and their associated glycans at the mucosal surface, how mucus-associated bacteria communicate

with the host and respond to changes in the physiological status of the host. Importantly, several conditions, such

as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colorectal cancer (CRC) or infections are

associated with alterations in mucus-associated bacteria and mucin glycosylation, so the mechanistic knowledge

we are gaining from our research can be of use for designing new biomarkers of disease and developing microbial

and nutritional strategies to restore health. The Juge Group is based at the Quadram Institute Bioscience (QIB)

within the Gut Microbes and Health (GMH) Institute strategic programme (ISP).

Current projects in the Juge group investigate:

The changes in mucin glycosylation and mucus-associated bacteria in health (across lifetime) and disease

(IBS, IBD and CRC)

The molecular mechanisms of adaptation of gut bacteria to the mucus niche

The modulation of gut barrier function by mucus-colonising bacteria using gut organoid-on-chip systems

The role of mucus-colonising bacteria in protecting from pathogen infection at the mucosal interface

The mechanisms underpinning the communication between mucus-colonising bacteria and the host immune

system

The role of mucin glycosylation and mucus associated bacteria in the gut-brain axis.

The development of novel biomarkers of disease and of glycan-based approaches targeted to the mucus-

associated bacteria to restore human health.

https://quadram.ac.uk/nathalie-juge/


.

https://quadram.ac.uk/nathalie-juge/



Discovering novel antibiotics to combat resistance

Due to the alarming increase in antimicrobial resistance, new antibiotics with novel mechanisms of action are desperately needed. Historically, the major source of antibiotics are soil microorganisms but in recent years the pipeline of such drugs has dried up. Does this mean that there are no new antibiotics left to be discovered? The answer is definitely not! Whole genome sequencing of microorganisms, including common ones that are intensively studied, has identified a vast number of biosynthetic gene clusters (BGCs) that encode for secondary metabolite production. However, the majority are silent, or are expressed at very low levels, under laboratory culture conditions. Our group is interested in unlocking these gene clusters, isolating novel natural products and testing them as antibiotics. An example of our research can be found in this recent publication: Epigenetic modulation of secondary metabolite profiles in Aspergillus calidoustus and Aspergillus westerdijkiae through histone deacetylase (HDAC) inhibition by vorinostat, https://doi.org/10.1038/s41429-020-0286-5. Our projects are multidisciplinary and involve a combination of bioinformatics, genomics, microbiology, epigenetics, natural products chemistry and biology. We use a variety of approaches to the discovery of novel metabolites ranging from the isolation of new species to optimisation of nutritional components in fermentation media to the use of human anticancer drugs in fungi and you will develop these skills as part of your research project.


Figure: Fermentation of an Aspergillus species in the presence of the histone deacetylase (HDAC) inhibitor vorinostat, clinically approved for the treatment of T-cell lymphoma, induces production of the anticancer compound phenylahistin.

https://doi.org/10.1038/s41429-020-0286-5



Upper gastrointestinal Surgery

General Surgery research in Norwich covers a broad range of areas from cancer research, perioperative care,

epidemiology, microbiology and robotic surgery. We work in close collaboration with the Norwich Medical School,

clinical researchers and scientists at the Bob Champion Research and Education Building and the Quadram

Institute.

Preoperative cardiopulmonary fitness may protect against the risk of postoperative complications after major

surgery. We are currently running a multi-centred observational study across 15 UK hospitals investigating the

association between preoperative cardiopulmonary fitness and the risk of postoperative mortality after

oesophagectomy.

Poor preoperative glycaemic control has been shown to be independently associated with adverse postoperative

outcomes. In the largest study of its kind, we are using both genetic and blood biochemistry information from the

UK Biobank to investigate the association between hyperglycaemia and postoperative complications.

There is increasing evidence that the biliary microbiome may play a role in gallstone formation. Advances in

sequencing and bioinformatics have made shotgun metagenomics the most detailed approach to understanding

the microbiome of the biliary tract. In collaboration with the Quadram Institute of Bioscience we are using shotgun

metagenomics sequencing, phylogenetic profiling and microbial genome analyses to elucidate the role of the

biliary microbiome in gallstone formation and disease.

Peritoneal metastasis develops in more than 50 % of gastric cancer patients. Median survival without treatment is

3-7 months. Delivering chemotherapy directly into the peritoneum is an approach with improved tissue

concentrations and reduced toxicity compared to systemic treatment. Pressurised Intraperitoneal Aerosol

Chemotherapy (PIPAC) has been shown to be an effective mode for intraperitoneal drug delivery. We are

generating data to justify and inform a large definitive trial to determine if PIPAC should be offered as a treatment

option for patients with an otherwise dismal prognosis.




Medical Microbiology

Molecular diagnosis of infectious disease Current research interests are in the molecular diagnosis of infectious diseases with a particular focus on the utility of next generation sequencing (NGS) for the diagnosis of complex clinical syndromes such as sepsis and respiratory tract infections. Currently, NGS is being used in centralised national reference laboratories to type referred bacteria but is not yet

available for routine diagnostic laboratories. Technologies under development will radically change this landscape,

reducing cost and removing the need for expert operators. Oxford Nanopore are developing one NGS technology,

the MinION device, which is expected to be available in 2014 and will work through the USB port of a computer.

Such technological advancements will move NGS from being a research and reference laboratory technology to

being something that can be used for the rapid, routine profiling of pathogens in clinical samples, possibly at the

point of care. The challenges to implementation are

sample preparation and data analysis. NGS

platforms are not optimised for the enrichment of tiny

amounts of pathogen nucleic acid from a vast excess

of human nucleic acid, as applies, for example, in the

investigation of bloodstream infection. We intend to

facilitate this leap in technology by developing

methods for preparing routine biologicals.


Antimicrobial resistance

Bacterial resistance to antimicrobials is becoming a global crisis with

pathogens now commonly being isolated that are resistant to the first

choice antibiotics we use to treat infections. Antibiotics are crucial to

treat infections but are also needed to provide prophylaxis allowing

invasive surgeries and immunocompromising therapies such as

common cancer treatments. Loss of the utility of antibiotics affects

almost all medicine. We investigate how bacteria are able to become

resistant to antibiotics (and antiseptics and disinfectants used in

infection control) and under which conditions exposure to antibiotics

does and does not result in resistance emerging. We study both real

world populations of isolates and mutants selected in controlled

laboratory experiments to understand resistance. We aim to develop

improved strategies to use current drugs in a way that won’t select

resistant mutants and to help design new treatments to treat

resistant bacteria.





Antibiotic resistance The main research focus of the Livermore lab is antibiotics and pathogen resistance. Research is centred on β-lactamases, their activity and bacterial resistance strategies including studies on hyper-resistant β-lactamase-hyper-producing mutants of Enterobacter. Other research relates to resistance epidemiology; leading teams investigating the molecular biology behind rises in MRSA, ciprofloxacin-resistant gonococci, carbapenemase-resistant Acinetobacter spp., cephalosporin-resistant E. coli and, latterly, carbapenemase-producing Enterobacteriaceae. Other current interests centre on the rapid detection of resistant bacteria in clinical samples and how this information can be used to improve patient treatment and antibiotic stewardship. Contact: [email protected]

Genomic microbiology

Our research is centred on the use of bacterial genomic data in clinical and public health microbiology; in particular the development of sequence based tools for the diagnosis and molecular epidemiology of infectious disease. We are establishing an evidence base for the association of a bacterial species (or sub-species) with any given infection. Our current Norwich based research projects include the linking of Staphylococcus to prosthetic joint infection, Clostridium to outbreaks of antibiotic associated diarrhoea and specific strains of Pseudomonas aeruginosa to antibiotic resistant biofilm associated respiratory infection.

We have a very active collaboration with Public Health England to develop the use of metagenomic DNA sequencing for pathogen discovery and outbreak detection, as well as with the Jos University, Nigeria to look at Salmonella epidemiology and antibiotic resistance. For MRes students we offer specific experimental plans within each project that can be carried out to completion within the one year time frame; the work adds incremental information towards publication. We also encourage undergraduates to be part of our research effort and MRes students are expected to help with their supervision. Contact: [email protected] or [email protected]

Phylogenetic tree of Staphylococcus coloured by species

Dark Blue, is Staph. Epidermidis





The evolution and spread of antibiotic resistance

Bacteria can become resistant to antibiotics through a number of different mechanisms. These include intrinsic

mechanism that all members of the bacterial species possess and that they switch on or ‘ramp up’ when exposed

to antibiotics, and mechanisms that the bacteria acquire from external sources that can then be exchanged

between bacteria.

My work centres on understanding which mechanisms bacteria are using to become resistant to antibiotics, and

how these are evolving and being transferred in bacterial populations. An example of current work is investigating

the effect of non-antibiotic drugs, such as cancer

chemotherapies, on promoting antibiotic resistance. Many

drugs used in healthcare coincidently have antibacterial

properties, and therefore bacteria develop resistance

against these. However, in doing so, some bacteria can

become more resistant to antibiotics at the same time, even

without having been exposed to any antibiotics. This ‘cross-

resistance’, where exposure to one drug (e.g. a cancer

chemotherapy) causes resistance to a different drug (e.g.

an antibiotic) is not well understood despite its potential to

have a major impact on the evolution and spread of

antibiotic resistance. By understanding how different drugs

cause cross-resistance to antibiotics we will gain a more

holistic view of antibiotic resistance that can be exploited in

the design and development of new drugs, and in the

management and use of existing drugs.


Emerging infectious disease The epidemiology of emerging infectious disease especially regarding outbreaks and epidemics linked to environmental factors. Research in the Hunter group has been focussed in the spread of infection by drinking water and insect vectors, the role of recreational water contact and food, climate conflict and other causes of rapid change. But a broader interest in zoonotic diseases, disease reservoirs and transmission pathways has developed during recent years working with SGOs like WHO and NGOs including MSF. Currently conducting case-control and other epidemiological studies in the UK, Europe and the developing world. Particular interest in risk assessment and risk communication Contact: [email protected]




Tropical Medicine

Parasite virulence

Infectious disease remains the major cause of illness and mortality especially of infants worldwide but disproportionately affect those in tropical regions the developing world. At UEA we are particularly interested in interventions to diagnose and prevent waterborne and vector borne diseases which are often most prevalent in the tropical areas but which continue to represent a threat to the UK population. Protozoan parasites cause many of the most widespread infections; most are benign, but many are deadly. Virulence factors determine what makes one infection deadly, while another is asymptomatic, as well as the extent and type of symptoms and pathology observed. We are interested in determining which parasite proteins are virulence factors and how we can exploit their identification for diagnosis of virulent strains, therapy and prevention. Current projects are directed towards understanding which virulence factors are associated with host range for cryptosporidiosis and trichomoniasis, with cell invasion for leishmaniasis and with enteric pathology for giardiasis. Opportunities exist for students to identify virulence factors from genomic analyses, to culture and transfect

parasites and host cells and to evaluate the function of the proteins they identify and their role in pathogenesis.


Antimicrobials

My research aims to identify synthetic and natural compounds with anti-microbial activity against neglected tropical diseases (e.g. human African trypanosomiasis or sleeping sickness) and fungal infections (e.g. candidiasis). My work focusses on the anti-microbial activity of compounds that inhibit cysteine proteases, proteasomes or topoisomerase. We test antimicrobial activity using bloodstream forms of Trypanosoma brucei, the causative agent of human African sleeping sickness, and Candida albicans, a causative agent of superficial fungal infection of the mucosa and skin. Compounds are tested in cell culture and the effect of the compounds on parasite and fungal cells are monitored by cell counting and/or spectrophotometrically by measuring absorbance. The effect of inhibitors on the targeted enzyme is determined by activity assays using substrate specific for the enzyme. Contact: [email protected]




Nutrition


Nutrition

RESEARCH AREA OVERVIEW Our mission is to conduct world-leading nutrition research which spans from fundamental mechanistic studies to large pragmatic trials in healthy participants and ‘at risk’ groups. Our research will help deliver the government Ageing Grand Challenge goal of increasing healthy life expectancy by five years by 2035.

We investigate the impact of key dietary components and dietary

patterns on health and risk of major age-related chronic diseases, in

particular cardio-metabolic health, musculoskeletal health, cognitive

health and dementia, micronutrient status and prostate cancer.

Key Research Interests include:

Flavonoids and their metabolites, and cardio-metabolic and

cognitive health

n-3 fatty acids, metabolism and cognition

Gut-liver-brain axis and the role of the microbiota

Micronutrient status, health and malnutrition e.g. iron and

vitamin D

Dietary fibres and glucose metabolism

Nutrient-gene interactions and personalised nutrition

Relevant Links: https://www.uea.ac.uk/medicine/research/cardiometabolic/nutrition-and-preventive-

medicine


Current Research Opportunities

Anti-cancer effect of isothiocyanates – Dr Yongping Bao

The impact of n-3 fatty acids and APOE genotype on cardiovascular and cognitive health – Prof Anne Marie Minihane

Musculoskeletal & nutrition research – Dr Inez Schoenmakers, PhD

Molecular Nutrition of the gut-liver-brain-axis – Prof Michael Muller

Public Health Nutrition

Nutritional epidemiology – Prof Ailsa Welch

Dehydration in older adults – Dr Lee Hooper

https://www.uea.ac.uk/medicine/research/cardiometabolic/nutrition-and-preventive-medicine

https://www.uea.ac.uk/medicine/research/cardiometabolic/nutrition-and-preventive-medicine



Anti-cancer effect of isothiocyanates (ITCs) The main focus of Dr Bao’s team is to determine doses of Isothiocyanates (ITCs) that are optimal for health, and

to investigate interactions with other nutrients in the modulation of key genes that affect cell proliferation, migration

and invasion. The work will contribute to the advancement of knowledge regarding the benefits and risks of dietary

bioactives.

ITCs derived from glucosinolates from cruciferous vegetables, possess chemo-preventive properties. ITCs have

been shown to exert antioxidant effects by the induction of the NF-E2-related factor-2 (Nrf2) transcription factor,

which activates the transcription of various antioxidant genes upon binding to the antioxidant response element

(ARE) in their promoters. The Nrf2-ARE

pathway is typically induced in response to

oxidative stress, against which it initiates a

major cellular defence mechanism. This

protection is very important in preventing

cancer. However, the overexpression of

Nrf2 in cells that are already cancerous has

the potential to promote their chemo

resistance.


The impact of n-3 fatty acids and APOE genotype on cardiovascular and cognitive health The research group’s primary focus is investigating the independent and

interactive impact of dietary/components (in particular marine n-3 fatty

acids and plant based Mediterranean style diets) and common genotypes

on cardiovascular and brain health (Alzheimer’s Disease risk).

The majority of the work uses randomised controlled trials (RCTs) with the

‘human’ interventions complemented by cell and rodent studies and

molecular biology approaches to inform the RCTs and investigate the

mechanisms underlying gene*diet*health associations. It is hoped our work

will contribute to the future personalisation/stratification of nutrition

recommendations and therapeutics based on an individual’s genetic profile.





Musculoskeletal & nutrition research

Inez Schoenmakers’s research is focussed on the investigation of calcium, phosphate and vitamin D metabolism,

particularly in relation to bone health. This research aims to investigate the metabolic processes that underpin the

development and maintenance of a healthy bone phenotype and how these are modulated by pregnancy, ageing,

kidney function, nutrition and ethnicity.

A major part of my current research investigates the renal-bone axis in the ageing population and how this relates

to the development of frailty. We investigate how this relates to micro-nutrient deficiencies.

My research offers opportunities to engage with pre-clinical research, lab-based projects and data analyses.




Molecular nutrition of the Gut-Liver-Brain axis

Research in the Müller group is directed towards getting an in-depth understanding of the mechanisms

underpinning the role of nutrition in controlling health. We will use the knowledge we acquire to develop efficient

strategies to prevent diet-related conditions, which include liver disease, cancer and cardiovascular disease.

These strategies may include probiotics, food bioactives, specific bile acids or drugs that target specifically the

small intestine to improve health and prevent systemic diseases.

We are currently facing significant human health and societal challenges that are linked to our unhealthy food

patterns and lifestyles. One of the organs playing a vital role in health maintenance is the intestine. In the small

intestine, food is processed, further digested and selected components are efficiently absorbed. The largely

indigestible remnants that pass the SI and enter the colon are partly fermented by the resident microbiota.

Compromised functionality of the intestine has been linked to several metabolic complications.

The important role of nutrition for the intestine, the gut microbiota and the gut liver axis is increasingly recognised.

However, to our knowledge, the exact mechanisms underlying the complex interaction of the food-microbiome-

host system in the different highly specialized regions of the small and large intestine remain largely unknown.

Our research aims to define the specific role of the microbiota in the differential responses of the small intestine

to diets with different dietary fibre content.

We are studying how diet-related changes in the small intestinal bile acid metabolism impact enterohepatic

functions and the functionality of the liver. We will also define the role of small intestinal metabolism for the aging

phenotype of the gut-liver-brain axis.

By targeting the small intestinal microbiota and its metabolism, we will characterise the reversibility of detrimental

age-related changes in the gut-liver-brain axis.

Interdisciplinary expertise allows us to apply our molecular nutrition research to molecular biology techniques and

in vivo studies using various mouse models a broad range of different methodologies like NGS, metabolomics

(with a focus on bile acids), miRNA, Transcriptome, 16S microbiome analysis and the related systems biology-

based data integration.




Public Health Nutrition

Nutritional epidemiology

Ailsa’s research focuses on nutritional epidemiology to

understand the relationship between diet and ageing, with a

particular focus on nutrition, muscle loss, osteoporosis and

fracture risk; this research feeds into prevention for public

health.

Ailsa also researches the impact of and developing nutritional

public health interventions. The research will be based on using

datasets with detailed information on diet and disease risk

factors (for instance the EPIC-Norfolk cohort study). It could also

involve evaluating local public health interventions with the

Norfolk County Council, with some contact with participants.


Dehydration in older adults .Lee Hooper carries out innovative research on low-intake dehydration in older adults living in the community

and in residential care homes. Student research projects may include:

data collection for and/or analysis of primary research with older adults assessing the diagnostic accuracy of signs of early dehydration,

carrying out systematic reviews in the area of low-intake dehydration in older adults, or

analysis of systematic review data on dietary fats and health outcomes

Research with Lee’s team offers an introduction to low-intake dehydration in the elderly, a chance to experience

research in a care home setting, and training in systematic review and/or diagnostic accuracy methodology.

Students may choose to participate in an on-going systematic review or secondary data analysis.

To access the Hydrate group go to: https://www.uea.ac.uk/medicine/research/publichealth/health-services-and-

primary-care/DrinKit

For further information on our dehydration research: http://driestudy.appspot.com/index.html, and for recent

publications see: https://people.uea.ac.uk/l_hooper/publications.



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Diabetes and Endocrinology


Diabetes and Endocrinology


Diabetes and endocrinology research opportunities include diabetes related foot disease and the experience,

and management of, patients with diabetes within hospitals. Other researchers have developed in vitro model

systems and three-dimensional models to understand the role played by inflammation in the development of

a number of pathological conditions.


Diabetic foot - Dr Ketan Datariya

Inflammation and disease – Prof Jelena Gavrilovic

Epigenetic Control of Development of Diabetes – Dr Zoe Waller

Diabetic foot Dr Dhatariya leads one of the largest diabetic foot clinics in the East of England seeing over 6000 patients per year. Over the last 5 years he and his podiatry team supervised over a dozen student projects on several aspects of diabetes related foot disease. Diabetes related foot disease remains the most frequent ‘diabetes specific’ reason for an acute hospital admission, and £1 in every £150 spent in the NHS in the UK is spent on the ‘diabetic foot’. His second major interest is hospital in patients with

diabetes. Across the UK, over 20% of all inpatient

beds are occupied by someone with diabetes. They

are not in hospital because of their diabetes, they just

happen to have it in addition to whatever else is

wrong with them. Having diabetes as an inpatient is

associated with an increased length of hospital stay,

lots more complications of their underlying condition,

and eventually a greater expense to the NHS. Dr

Dhatariya has been an author on many of the

national guidelines on the management of inpatients

with diabetes, and led the recently published world’s

largest survey on the management of diabetic

ketoacidosis.

He also has a special focus on patients with diabetes

undergoing surgery.




Inflammation and disease

We are interested in understanding the role played by inflammation in the development of a number of pathological conditions. We have developed complex in vitro model systems that allow us to mimic the in vivo environment as closely as possible. Some examples include the use of 3-dimensional systems to study the invasion of monocytes, macrophages, adipocytes, endothelial cells and tumour cells through complex 3-D collagen matrices and micro-mass cultures made from cartilage and chondrocytes. We assess inflammatory responses by exploring cell migration and the expression of metalloproteinases (MMPs, ADAMs and ADAMTS enzymes), as well as the connective tissue (CCN) family of growth factors implicated in osteoarthritis and fibrosis. We interact closely with several clinicians including Dr Jeremy Turner, Dr Martin Lee and Professor Simon Donell. Contact: [email protected]

Epigenetic control of development of diabetes

There is the need for a better understanding of epigenetic control of development of diabetes. The insulin

minisatellite or insulin-linked polymorphic region (ILPR) resides in the promoter region of the gene coding for

insulin (INS). The region consists of a 14 base pair tandem repeat DNA sequence of 5'-ACAGGGGTGTGGGG-

3'/3'-TGTCCCCACACCCC-5' and is located 363 bp upstream of the transcription start site of INS. Mutations or

shortening in the length within the sequence of the ILPR has been linked to the development of both insulin-

dependent (type 1) and type 2 diabetes. The ILPR can form alternative DNA secondary structures such as G-

quadruplexes and i-motifs. This project would aim to learn more about how DNA structure affects the ILPR and

expression of INS.





Musculoskeletal Biology and Surgical Anatomy


Musculoskeletal Biology and Surgical Anatomy

RESEARCH AREA OVERVIEW In this area, there are opportunities to access the state of the art technologies of the Bio-Analytical facility at BCRE, devoted to the study of bone disease. Other research groups apply biochemistry and molecular biology to understand skeletal muscle regeneration, and the fabrication of synthetic biomaterials to enhance surgical treatment of tendon injury. Current Research Opportunities

Metabolic bone disease and calcium disorders – Prof William Fraser

Stem cells for skeletal muscle repair – Prof Ulrike Mayer and Prof Ernst Poschl

Osteoarthritis drug development – Dr Linda Troeberg

3D modelling of joints using clinical imaging data – Dr James Mackay and Dr Tom Turmezei

Autoimmunity and inflammatory bone loss disorders – Prof. Nicole Horwood

Metabolic bone disease and calcium disorders Research opportunities exist exploring the clinical diseases of Osteoporosis, Paget’s Disease of Bone,

Osteomalacia (vitamin D deficiency) and hyper/hypoparathyroidism. Both diagnostic and therapeutic projects are

available.

The Bio-Analytical facility at BCRE is equipped with state of the art technology able to measure all molecules of

interest in the regulation of bone and calcium metabolism. We have recently developed technology for the

measurement of vitamin D metabolites and several projects are available looking at the role of these metabolites

in health and disease. In particular the relevance of

these measurements in predicting outcome of vitamin

D supplementation in sportsmen, army recruits,

patients with osteoporosis, osteomalacia and FGF23

related disorders such as hypophosphataemic rickets.

Development and clinical application of FGF23,

AntiOPG, Sclerostin and PTHrP assays are ongoing

projects. Recent developments in miRNA technology

as applied to bone disease and bone/cartilage

tumours are becoming more important and an

expanding area of interest of the unit.

https://www.uea.ac.uk/bioanalytical-facility Contact: [email protected]

https://www.uea.ac.uk/bioanalytical-facility



Stem cells for skeletal muscle repair

We are using genetically modified mice in combination with histology,

fluorescence activated cell sorting (FACS), molecular biology methods

and biochemical techniques as research tool to address our research

question. We aim at understanding the function of these two types of

stem cells by defining the differences of their specific phenotypes,

expression patterns and differentiation capacities. These results will

help to understand the regenerative processes in muscle in more detail

during normal repair as well as in various muscle diseases.

Skeletal muscle is a terminally differentiated tissue, but has the remarkable capability of continuous and accurate

repair after injury due to exercise, trauma or disease. Muscle regeneration is mainly dependent on highly

specialised muscle stem cells called satellite cells. These stem cells are specified during development and are

crucial for us to gain muscle mass in postnatal life. Satellite cells become dormant later in life until muscle damage

occurs and regeneration is needed. More recently, blood vessel-associated stem cells, called pericytes, have been

proposed to represent another source of stem cells for skeletal muscle regeneration. Our research aims to

determine the signals that are required for differentiation of these stems cells into muscle cells. This knowledge

will be important for developing strategies to combat muscle wasting diseases, such as during Duchenne muscular

dystrophy, or muscle loss associated with ageing.

Contact: [email protected] or [email protected]

Osteoarthritis drug development Osteoarthritis is a chronic degenerative joint disease that affects 1 in 5 people over the age of 50. Despite this high prevalence, treatment options for osteoarthritis are limited. This group, led by Linda Troeberg, aims to develop novel therapies for the disease by defining the molecular events that lead to joint damage. Understanding the molecular mechanisms that drive inflammation and extracellular matrix remodelling may also help us treat other chronic conditions, including rheumatoid arthritis and age-related macular degeneration. Our research is of relevance in the fields of orthopaedics, rheumatology, ophthalmology, endocrinology and gerontology. Research opportunities include:

Investigating what molecular changes in the joint increase risk of osteoarthritis as we age

Testing whether dietary supplements and chemical inhibitors can block cartilage damage

Evaluating chemical inhibitors for treatment of age-related macular degeneration Contact: [email protected]





3D modelling of joints using clinical imaging data

We use novel 3D surface modelling and image

analysis techniques to analyse clinical computed

tomography (CT) and magnetic resonance (MR)

imaging in patients with osteoarthritis (OA). Our

approach has been developed in collaboration

with the University of Cambridge Department of

Engineering

These methods provide improved insight into the

pathogenesis of OA as well as better

assessment of disease progression and

response to treatment.

OA is a very common condition with a huge

unmet need, so this work has the potential to

make significant impact.

Projects are available working with both CT and

MR imaging data, including from the large

prospective multicentre APPROACH (EU) and

MOST (US) studies.

Projects would involve using advanced imaging

analysis software. Full training will be given, the

software is user-friendly and support will always

be available. However, a degree of pre-existing

computer literacy would be helpful.

The project could include training in basic programming in R and MATLAB for image data processing if this

was an area of interest for the candidate.

Current Research opportunities:

We will be interested in an MRes research student for the 2020/21 year.





Autoimmunity and inflammatory bone loss disorders

Prof Nikki Horwood has recently joined UEA Medical School as a research supervisor for the MRes course. Prof

Horwood is a molecular and cellular biologist who specializes in the loss or gain of bone mass during disease.

She studies the prevalence of immune cells and their soluble mediators, as major regulatory factors in skeletal

biology which has become increasingly evident in the last 20 years. Osteoimmunology seeks to define the roles

and interactions of immune cells with skeletal cells to understand their relative contributions to musculoskeletal

diseases. She has recently been appointed at UEA after nearly two decades at the Kennedy Institute of

Rheumatology (Imperial College London and University of Oxford). Bone loss is a problem in many inflammatory

diseases and there are limited therapeutic options to replace bone once it has been lost. Her research focuses on

the underlying cellular causes of bone loss and identification of potential therapeutic options.

Current Research Questions

1. Determining the role of natural killer cells in the initiation of autoimmunity. 2. How inflammation can cause both bone destruction and bone formation in ankylosing spondylitis? 3. How the tissue repair cycle is initiated and what happens if it fails to switch off? What are the roles

of different macrophage subsets in bone turnover? 4. What factors control bone marrow cell fate and their correlation to disease susceptibility in the aged? 5. Are there ways to reprogram bone forming osteoblasts to produce more bone? 6. Altering the bone microenvironment in bone marrow cancers to reduce disease burden and preserve

bone architecture. 7. How to separate the anti-inflammatory properties of glucocorticoids from their adverse effects on

bone destruction? 8. Ways to speed fracture repair in healthy and osteoporotic bone

These areas will be suitable to all the students interested in pursuing an academic career, especially in

specialities like endocrinology, rheumatology, metabolic medicine and orthopaedics. She is very happy to meet

and discuss specific projects with potential MRes intercalation candidates.




Oncology and Haematology


Oncology and Haematology


Angiogenesis and solid cancers – Dr Stephen Robinson

Prostate cancer genetics – Prof Colin Cooper and Dr Dan Brewer

Melanoma and neural crest development – Dr Grant Wheeler

Microtubule an epithelial cell differentiation in health and cancer – Dr Mette Mogensen

Proteases and breast cancer metastasis – Prof Dylan Edwards

Chemopreventive agents in the diet – Prof Dylan Edwards and Prof Cathie Martin

I-motif in Nrf-2 – Dr Zoe Waller

Melanoma and pigment cell research – Dr Chris Morris, PHA

Angiogenesis and solid cancers

The recruitment of a blood supply is critical for solid cancers to grow beyond a very small size. Once this

vasculature is established (by a process called angiogenesis) tumours become much more aggressive, they begin

to invade nearby tissues, and they may eventually spread to distal sites throughout the body (metastasise). Thus,

angiogenesis presents itself as a key target for cancer therapeutic delvelopment.

To date, the drugs that have been developed as anti-angiogenic agents are showing only limited effect in the clinic. The Robinson group works on understanding how cells of the blood vasculature respond to angiogenic signals derived from the cancer, in an effort to develop better anti-angiogenic therapies. Current goals are:

To understand how movement of the vasculature toward a growing tumour is orchestrated; who are the essential molecular players that might serve as drug targets?

To determine the short- and long-term impacts of current angiogenic interventions that are designed to ameliorate cancer growth and spread; are they good targets?

To develop better anti-angiogenic strategies.




Prostate cancer genetics

A critical problem in the management of prostate cancer is that it is not possible to distinguish reliably aggressive

from non-aggressive disease at the time of diagnosis. This results in considerable overtreatment of this disease

such that many men with indolent disease are given radical treatments (surgery, radiotherapy) unnecessarily and

made impotent. The current work of the Cancer Genetics Team, led by Prof. Cooper and Dr. Brewer, are focused

on identifying biomarkers to help solve this problem and exploring the molecular evolution of prostate cancer. We

do this through the generation of large data sets using novel approaches in the lab, mainly in the ‘omics space,

and the application of cutting-edge data analysis techniques. Our work has strong components of both data

generation and bioinformatics analysis. Current projects include:

The collection and analysis of sequencing data (genomic, transcriptomic and epigenomic) from 250 prostectomy samples (ICGC Prostate UK project and PanProstate Cancer Initiative).

Identification of biomarkers to predict disease aggressiveness at diagnosis from urine.

Exploring the role of bacteria in prostate cancer.

Identifying and exploring subtypes of disease in prostate cancer through the analysis of large scale expression data sets.


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Prognostic

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Metastatic

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Clonal Expansions

EMT

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Development of multip le cancer lineages




Melanoma and neural crest development The Wheeler group works on the molecular events that govern the origin and migration of different cell types within

developing embryos. We use tadpoles from Xenopus

laevis (African Clawed Frog) as our model system. To

investigate these processes we are using a combination

of embryological, molecular developmental biology,

imaging and chemical genetic approaches.

We are also interested in developing Xenopus as a potential tool in the drug screening and discovery process. We

are mainly focused on looking at the differentiation and migration of Neural Crest cells especially with respect to

pigment cell development and melanoma growth. Current projects include:

Using chemical genetic screens to determine a role for epigenetic modifiers in neural crest development and migration.

Screening small molecule libraries for inhibitors of pigment cell development to gain insight into neural crest and also to identify inhibitors of melanoma growth.

Developing in vivo toxicity assays for small molecules and nanoparticles. Contact: [email protected]

Microtubule an epithelial cell differentiation in health

and cancer

Microtubules are tubular filaments that are vital for cell survival with many critical functions including cell division

and intracellular transport being dependent on them. They are also important for cell differentiation with dramatic

reorganization of the microtubule network driving changes in cell architecture and supporting specialised functions.

For example, the formation and maintenance of polarised transport epithelia such as that lining the gut is

dependent on microtubules. The correct alignment of the microtubules is critical for normal tissue function with

defects in polarisation leading to loss of function, cell invasion and cancer. Microtubules are therefore often targets

of cancer drugs with the stabilising taxanes being classic examples.

Our aim is to identify the molecules and mechanisms involved in microtubule organisation and maintenance. Funding from BigC and Breast Cancer Now is helping us to better understand the mechanisms responsible for loss of epithelial polarity and progression to an invasive cancer state. We use 3D in vitro gut organoids that closely mimic the in vivo gut architecture and organogenesis as well as cancer cell lines in combination with GFP- and RNAi technology and immuno-localisation and confocal, multi-photon and live time-lapse microscopy to pursue these aims.Developing in vivo toxicity assays for small molecules and nanoparticles. Contact: [email protected]




Proteases and breast cancer metastasis

Metastasis is the main cause of death for cancer patients. Our group is studying the roles of extracellular proteases

in regulation of the tumor microenvironment, and how these enzymes contribute to tumour growth and metastasis.

It had previously been thought that these enzymes promoted cancer by acting as molecular scissors to cut a path for the invading cells through the extracellular matrix (ECM) but we have found that they work in many different

and subtle ways – essentially, they control the microenvironment within tumours, influencing growth, cellular organization, immune function, angiogenesis (blood vessel formation), invasion and metastasis. Indeed - as we have found - some proteases such as matrix metalloproteinase-8 (MMP8) actually stop cancers from spreading. We have developed a number of tools to evaluate the “degradome” – the repertoire of proteases and related molecules that cells and tissues deploy during normal and pathological tissue remodeling processes. We are interested in how these degradome genes act, how they are controlled, and their development for diagnosis and for novel therapies.

Particular projects underway at present include:

Studies of the interplay between ADAMTS metalloproteinases and Syndecan proteoglycans in signalling and adhesion mechanisms in breast cancer.

Regulation of the innate immune system by the anti-metastatic protease MMP8.

Protease involvement in angiogenesis

Use of nanoparticles for delivery of cancer therapeutic agents. Contact: [email protected]

Chemopreventive agents in the diet This work is undertaken in collaboration with Prof Cathie Martin at the John Innes Centre, who has engineered

strains of tomato that are enriched in particular plant polyphenolic compounds. We have demonstrated that

extracts from these plants cause selective apoptosis of cancer cells. We are interested in the mechanisms by

which these dietary polyphenolic compounds influence cancer cell survival and apoptosis

The research would primarily be wet lab-based but there are opportunities for bioinformatics studies related to analysis of cancer gene and gene expression databases. For further details on the work of the lab go to the following links: http://www.uea.ac.uk/biological-sciences/People/Academic/Dylan+Edwards http://www.researcherid.com/rid/B-4734-2009



http://www.uea.ac.uk/biological-sciences/People/Academic/Dylan+Edwards

http://www.researcherid.com/rid/B-4734-2009



I-motif in Nrf-2

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key

regulator of cell detoxification, which maintain homeostasis in

healthy cells and promote chemoresistance in cancer cells.

Controlling the expression of this transcription factor is therefore

of great interest. A cytosine-rich quadruplex-forming sequence

has been identified on the opposing strand downstream of the

Nrf2 promoter, which may play, or be made to play, a role in the

expression of the gene. i-Motifs are non-canonical quadruplex

secondary DNA structures defined as two parallel stranded duplexes held in an antiparallel manner by the

intercalation of hemiprotonated cytosine–cytosine+ base pairing. These alternative structures may play a role in

gene expression (whether genes are switched on or off) and also in the development of genetic diseases such as

cancer. By targeting these alternative DNA structures, this could allow for more specific interventions and

therapeutics compared to traditional chemotherapies. This project will explore targeting the i-motif in Nrf-2.


Melanoma and pigment cell research

Research in my group addresses a number of areas

in skin cancer and skin pigmentation. Melanoma

projects include the identification and validation of

new biomarkers/drug targets in melanoma. We use

phage display screening technology to map the

surface of melanoma cells with the aim of identifying

cell surface proteins that are over-expressed in

melanoma cells. We have recently identified

proteins that are uniquely over-expressed in

melanoma and have shown them to drive a pro-

metastatic phenotype in melanoma cells. These

proteins have the potential to serve as new disease

biomarkers in melanoma.

Skin pigmentation projects in the lab are

collaborations with Prof. Tom Wileman (MED). We

are working with cellular models to better understand how melanin pigment granules are secreted from the

pigment-producing melanocytes and trafficked into epidermal keratinocytes to serve as a barrier to UV radiation

induced DNA damage. The projects involve the isolation and culture of melanocytes and keratinocytes from mouse

models and studying their behaviour using live cell and fixed cell fluorescence microscopy. This project has the

potential to be adapted to pigment cell diseases such as Griscelli Syndrome.





Cardiovascular Research


Cardiovascular Research


Cardiovascular research is a growing activity at University of East Anglia and Norfolk and Norwich University

Hospital and across the Norwich Research Park. All researchers mentioned in this summary would be

delighted to discuss with students about research in this field and very happy to be contacted about

opportunities. Such opportunities could be for both SSS and importantly for MRes related research.


Heart function/heart failure – Dr Vass Vassiliou

Acute coronary syndromes – Prof Marcus Flather and Dr Alisdair Ryding

Adult congenital heart disease – Prof Marcus Flather

Interventional Cardiology – Dr Simon Eccleshall and Dr Vass Vassiliou

Valvular Heart Disease- Dr Vass Vassiliou

The impact of n-3 Fatty Acids and APOE Genotype on Cardiovascular and Cognitive Health – Prof Anne-Marie Minahane

Stem Cell Models of Heart Disease - Dr James Smith

Heart function/ heart failure There is ongoing research on understanding the basic

mechanisms of cardiac contractility including energy

requirements and response to exercise are key aspects of this

work leading to an understanding of novel therapies to support

the failing heart.

The group has developed the concept of diastolic ventricular interaction (DVI) where right ventricular overload can impact on left ventricular function and is testing ways to improve this including pacing. Enhancing nitric oxide at a cellular level may lead to improved cardiac energetics and a randomised trial of nitrate supplements in dilated cardiomyopathy is underway to understand the mechanistic response to this therapy and safety.




Acute coronary syndromes Professor Marcus Flather is undertaking clinical and translational research projects in a wide range of cardiovascular conditions including acute coronary syndromes, heart failure and coronary revascularisation through national and international collaborations. Students can have access to datasets from ongoing and completed clinical trials and observational studies to undertake analyses for their MRes projects and for future publications. Examples of current work include:

1. Arterial Revascularisation Trial (ART). This is a large multi-centre trial of 3200 patients undergoing coronary artery bypass graft surgery comparing single versus bilateral internal mammary artery grafts

2. SENIORS: A study of 2100 elderly patients with heart failure randomised to the vasodilating beta blocker nebivolol or placebo

3. AIMS: A randomised trial of irbesartan in 160 patients Marfan Syndrome 4. Beta blockers in heart failure meta-analysis: individual patient data meta-analysis of all RCTs of beta

blockers versus placebo in heart failure in 18,200 patients 5. CARDia: Randomised trial of percutaneous coronary intervention versus coronary artery bypass grafting

in 510 patients with Diabetes

Adult congenital heart disease Analysis of a longitudinal database of clinical cases of adult congenital heart disease managed at Norfolk and

Norwich University Hospital has been undertaken to describe patient characteristics, treatments and outcomes

(Dr Leisa Freeman) as well as a more detailed analysis of the haemodynamics and cardiac structure and function

in collaboration with Guys and St Thomas’s Hospital. A new study is being set up to investigate early changes in

hepatic structure and function in patients with adult congenital heart disease in collaboration with Dr Simon

Rushbrook (NNUH and Norwich Medical School) using elastography (Dr Cathy Head, Dr Leisa Freeman).


Interventional cardiology Norfolk and Norwich University Hospital (NNUH) is one of the busiest coronary interventional centres in the UK.

Norwich has pioneered the introduction of Drug Coated Balloon (DCB) technology in which coronary stenosis are

dilated with DEB without the placement of a stent. NNUH has one of the largest case series of DCB treatment and

these cases are being analysed for a report that can inform future research (Dr Simon Eccleshall, Dr Vass

Vassiliou). Projects in acute coronary syndromes interventional programme are being carried out by Dr Alisdair

Ryding.

Valvular heart disease With an ageing population, valve disease is becoming a significant burden to the NHS services. Dr Vassiliou leads the work in identifying adverse predictors in patients with valve disease and mortality. This work is undertaken in collaboration with the Royal Brompton Hospital and specifically looks at the role of cardiac MRI and the presence of scarring in associating with mortality. Contact: [email protected]




The Impact of n-3 fatty acids and APOE genotype on cardiovascular and cognitive health

The research group’s primary focus is investigating the independent and

interactive impact of dietary/components (in particular marine n-3 fatty

acids and plant based Mediterranean style diets) and common genotypes

on cardiovascular and brain health (Alzheimer’s Disease risk).

The majority of the work uses randomised controlled trials (RCTs) with the

‘human’ interventions complemented by cell and rodent studies and

molecular biology approaches to inform the RCTs and investigate the

mechanisms underlying gene*diet*health associations. It is hoped our

work will contribute to the future personalisation/stratification of nutrition

recommendations and therapeutics based on an individual’s genetic

profile.


Stem cell models of heart disease

Fibrosis is a prevalent and hard-to-treat condition. Of all deaths in the developed world, 45% are associated with

chronic fibro-proliferative disease. Cardiac fibrosis disrupts the mechanical and electrical activity of the heart,

which can lead to sudden cardiac death. Many heart diseases,

such as hypertrophic cardiomyopathy (HCM), are associated

with a fibrotic phenotype.

This group led by Dr James Smith, uses human induced

pluripotent stem cells (hiPSCs) and CRISPR-Cas9 gene editing

technology, to create new human in vitro models of cardiac

disease. Gene edited hiPSCs can be differentiated to produce

force-generating cardiomyocytes, and secretory active cardiac

fibroblasts. We investigate the interplay between these cell

types, creating models that recapitulate the impact of cardiac

fibroblasts on cardiomyocyte function. The role of disease

causing mutations (including HCM mutations) can be

investigate in such models to gain better insights into these

diseases and identify new potential therapeutic targets.





Respiratory Medicine, Rhinology and Ear, Nose and

Throat


Respiratory Medicine RESEARCH AREA OVERVIEW This group has a programme of work investigating self-efficacy in patients with chronic disease such as bronchiectasis and other respiratory diseases. Researchers are exploring and evaluating options for improving self-efficacy and health related quality of life, through patient education and patient self-management plans (PSMP). Current Research Opportunities

Self –efficacy in respiratory disease – Prof Andrew Wilson

Rhinology and ENT – Prof Carl Philpott

Self-efficacy in respiratory disease

Living with chronic disease results in considerable financial and emotional burden for patients. Innovative methods are required to increase the quality of patient care, improve patient choice and provide care closer to home, in an expedient and productive manner. Modern healthcare approach encourages a change in the doctor:patient relationship from paternalistic to shared decision making. Self-efficacy is the confidence patients have in their ability to successfully deal with their condition and make decisions that affect their care.We have a programme of work investigating self-efficacy in patients with chronic disease and exploring options of improving self-efficacy though patient education and patient self management plans (PSMP). We have designed a PSMP for bronchiectasis called BET (see figure) and are currently evaluating its utility. Other workstreams investigate the influence of self-efficacy on health related quality of life. Opportunities are available to evaluate self-efficacy further in different contexts in patients with different respiratory diseases. Contact: [email protected]



Rhinology and ENT

The Rhinology and ENT Research Group led by Professor Carl Philpott has a portfolio of research ranging from

lab based to clinical and engagement projects. Currently active research includes chronic rhinosinusitis olfactory

disorders and cholesteatoma as subject areas with opportunities to develop research skills in collection and

processing of tissue samples, cytokine analysis, data interpretation, genetics, health economics, qualitative

analysis, recruitment to clinical trials, observational studies and public engagement and education. MRes students

will be supported in undertaking primary research activities as well as presenting their findings to national and

international meetings and contributing to the publication of research papers. The group receives funding from

various sources including NIHR which funds the £3.2 million MACRO programme grant for chronic rhinosinusitis.

Anyone interested in exploring an MRes should contact Kay Tate to arrange an appointment to see Professor

Philpott.




Mental Health and Dementia


Mental Health and Dementia RESEARCH AREA OVERVIEW Dementia is becoming one of the biggest burdens of our society with the aging population. There is an urgent

need to improve our clinical and research understanding of the underlying disease in dementia. Dementia

research topics at UEA take therefore a multi-disciplinary approach, linking bedside to bench research

approaches.


Mental health in the elderly – Prof Chris Fox

Underlying Genetics and Epigenetics – Dr Zoe Waller

Brain changes in dementia – Prof Michael Hornberger

Nutrition and dementia – Prof Anne-Marie Minihane

Mental health in the elderly Our research focuses on 3 strands: cause, care and interventions in dementia in primary, secondary, tertiary and social care. Current projects include (1) ‘Perfected’ which is developing an enhanced recovery pathway (care), (2) the use of large data sets allows us to extract causative factors in dementia (cause) and (3) develop prevention interventions trials such as use of minocycline and use of assistive technology (intervention). We have literature reviews to develop a new comorbidity tool for use as an App or tech platform-skills opportunity-

which advances students skills on literature analysis. We have qualitative projects in the PERFECTED study of

care in hospital in dementia and can provide data analysis from 3 projects funded by NIHR and Alzheimers society

looking at the harms and benefits of commonly prescribed medications and screening for dementia. These use

CPRD and CFAS datasets. Our website provides more detail.

https://www.uea.ac.uk/medicine/research/dementia.


Underlying Genetics and Epigenetics There is the need for better understanding of the underlying genetics and epigenetics (altered gene expression and activation) surrounding Alzheimer’s Disease to inform cutting-edge diagnostic and treatment options available for development. i-Motifs are quadruplex secondary structures formed from DNA sequences rich in cytosine, composed of parallel-stranded duplexes and held together by intercalated, hemi-protonated cytosine-cytosine base pairs. This project would aim to establish the function of a rare type of DNA i-motif forming sequence (C6) which are implicated in the progression and development of Alzheimer’s disease.


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Brain changes in dementia

Clinical symptomology and underlying brain changes are closely linked in dementia. Our research investigates the interactions of these clinical symptoms and their neural correlates, with a particular focus on behaviour, memory and eating changes via state-of-the-art neuroimaging methods. In particular we are interested in identifying the shared and unique clinical and imaging features across the most common dementias: Alzheimer’s disease, vascular dementia, frontotemporal dementia and Dementia with Lewy bodies. We have strong clinical links with neurological and old-age psychiatry clinical services in the region. Our research findings inform primary to tertiary clinical services and is particularly targeted towards better differential diagnosis and improved symptom prediction and management.


Nutrition and dementia Nutrition is a significant determinant of cognitive development and decline throughout the life-course. A number of dietary components, including marine n-3 fatty acids (and in particular DHA) and select plant bioactives, have emerged as having the potential to improve cognitive performance and reduce the risk and prevalence of dementia. In the Department of Nutrition and Preventive Medicine, a main area of research focus is investigating the independent and interactive impact of these dietary components and APOE genotype on cognition, brain volumes and blood flow, and circulating markers of cognitive health. An APOE4 genotype status, which occurs in 25% of the population, is the most prevalent genetic risk factors for Alzheimer’s Disease. The majority of the work uses human randomised controlled trials (RCTs), which are complemented by cell and

rodent studies and molecular biology approaches to inform the RCTs and investigate the mechanisms underlying

gene*diet*health associations. It is hoped our work will contribute to the identification of strategies to promote

’healthy’ brain ageing, and in particular in at-risk APOE4 individuals’.





Population Health, Primary

Care and Health Care Delivery


Population Health, Primary Care and Health Care Delivery

RESEARCH AREA OVERVIEW The focus of population health research is to improve health and quality of life through prevention and

treatment of disease and other physical and mental health conditions. Our work combines state-of-the art

research in several clinical, public health and health service fields: health economics, clinical trials,

epidemiology, health geography, and medical statistics and our research addresses a wide range of clinical,

health service and public health problems. We have particular strengths in research on: the organisation and

delivery of primary health care; diabetes; cardiovascular risk factors; obesity; smoking; musculoskeletal

disease; HIV; tuberculosis; respiratory disease; mental health; diagnostic screening; and environmental

influences on health.

MRes students can get good hands-on research experience and can produce original publishable papers

themselves, with expert guidance. For example, statistical analysis of pre-existing survey data already held

by academic staff, but yet not fully exploited, can answer interesting research questions in new ways.

Students can collect their own data using questionnaire surveys or by going through medical records. In

depth-interviews with individual patients, health professionals or groups of people can provide deeper insights

into issues and problems that are not captured by numerical evidence. It is quite feasible for students to

collect and to analyses these qualitative data themselves. Systematic reviews and meta-analyses (statistical

summaries) of previously published research are also feasible for students to do by themselves, often

producing high impact publications. With any of these methods, the process of identifying problems, asking

questions, defining hypotheses and analysing data provides transferable skills which can be used in many

different areas of medical research.

Relevant Links https://www.uea.ac.uk/medicine/research/publichealth

https://www.uea.ac.uk/medicine/research/publichealth/health-services-and-primary-care

https://www.uea.ac.uk/medicine/research/publichealth/epidemiology-and-public-health https://www.uea.ac.uk/medicine/health-economics-group/our-research Current Research Opportunities

Effectiveness, cost effectiveness and epidemiology

of health care – Prof Max Bachmann

Measuring population health – Prof Nick Steel

Musculoskeletal epidemiology - Prof Alex MacGregor (academic rheumatologist), Dr Max Yates (academic rheumatologist), Dr Jack Dainty (statistician), Dr Donnie Cameron (MRI physicist) and Prof Elena Kulinskaya (actuary/statistician in Computer Science)

Economic evaluation/cost effectiveness - Prof Garry Barton

Environmental influences and social on health – Prof Andy Jones

Economics of ageing – Prof Ruth Hancock

Economic evaluation methods – Prof Tracey Sach

Public health and clinical intervention – Prof Fujian Song

Addiction Research – Dr Caitlin Notley

Social gerontology – Dr Charlotte Salter

https://www.uea.ac.uk/medicine/research/publichealth

https://www.uea.ac.uk/medicine/research/publichealth/health-services-and-primary-care

https://www.uea.ac.uk/medicine/research/publichealth/epidemiology-and-public-health

https://www.uea.ac.uk/medicine/health-economics-group/our-research


Effectiveness, cost effectiveness and epidemiology of health care Max Bachmann is professor of health services research. He is a

public health physician interested quantitative evaluation of the

effectiveness and cost effectiveness of health care, especially of

primary care interventions intended to improve the health of

populations. Disease areas of interest include HIV, tuberculosis,

diabetes, and chronic illness in general. He works with South

African colleagues on a research programme to improve primary

care through training and clinical guidelines, based on a series

of randomised trials and related research. For medical student

research he is able to supervise systematic reviews and

synthesis of evidence about the effectiveness of health care, and

the epidemiology of these conditions. We may be able to extend

this to statistical analysis of epidemiological data.


Measuring population health

Professor Nick Steel leads the Health Services and Primary Care Research Group within the Public Health and

Health Services Research Theme in Norwich Medical School. His research interests focus on measuring heath at

population level with a view to improving the health and quality of life of people in need. He is currently working on

two major projects that offer excellent opportunities for quantitative analysis of existing data for MSc and PhD

students: the English Longitudinal Study of Ageing (https://www.elsa-project.ac.uk/), and the Global Burden of

Disease Study in England (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32207-4/fulltext

and http://www.healthdata.org/gbd).

Nick has also been involved with a local evaluation of

primary health care for vulnerable people, including the

homeless and migrants, and there may be

opportunities for further research in this area.

Figure: Global total number of deaths,1950-2017

(www.healthdata.org/gbd)



https://www.elsa-project.ac.uk/

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32207-4/fulltext

http://www.healthdata.org/gbd


http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=0ahUKEwi71vmMy-vNAhUrIcAKHfrUCwEQjRwIBw&url=http://www.scielosp.org/scielo.php?script%3Dsci_arttext%26pid%3DS0042-96862006000800016&psig=AFQjCNFj9d3I-TpmBYCIQ9XZClThZ6WQ6g&ust=1468332509640255


Musculoskeletal epidemiology In 2013, the Centre for epidemiology (CfE) Versus Arthritis was jointly awarded to Manchester University and UEA,

recognising the strengths and potential for musculoskeletal epidemiology research across the two institutions. This

has placed UEA and Manchester at the centre of a UK collaborative network in musculoskeletal epidemiology that

includes the universities of Oxford, Southampton, Keele, Nottingham, Aberdeen and Bristol. The UK Research in

Musculoskeletal Epidemiology (UK-RiME) partnership facilitates collaboration and partnership between these

institutions.

Here, at UEA within the centre for epidemiology, we are dynamic group with links to other national and international

centres. We included academic rheumatologists, statisticians, MRI physicists and computer scientists. In addition,

we collaborate with “wet-bench” scientists here at UEA. Our work includes descriptive and aetiological work on

the two large and long-running cohort studies based in Norfolk: The Norfolk Arthritis Register (NOAR) and The

European Prospective Study into Cancer and Nutrition (EPIC-Norfolk). NOAR was set-up in 1989 and represents

one of the longest and best-characterised inception cohorts of patients with inflammatory arthritis in Europe. EPIC-

Norfolk recruited participants between 1993 to 1997 and has an unrivalled rich phenotype.

In addition we have experience of working with other large datasets such as the CPRD, UK Biobank, UK Twins

Registry and National Joint Registry. We are always delighted to have intercalating medical students to work with

us on small, well contained projects which enhance studies of morbidity and disease progression within these data

sources. Other opportunities include pilot studies from translation work up to, and including, clinical interventional

trials.

The range of projects carried out address research questions across the life course of musculoskeletal disease,

and as such, would be suitable to all students interested in pursuing an academic career. Specialities particularly

aligned include: rheumatology, orthopaedics, public health, general practice and radiology. We are very happy to

meet and informally discuss research ideas with potential MRes students.

Contacts:

Prof Alex MacGregor (academic rheumatologist): [email protected]

Dr Max Yates (academic rheumatologist): [email protected]

Dr Jack Dainty (statistician): [email protected]

Dr Donnie Cameron (MRI physicist): [email protected]

Prof Elena Kulinskaya (actuary/statistician in Computer Science): [email protected]







Economic evaluation/ cost effectiveness

Professor Garry Barton’s main area of expertise is in the application and development of the methods of economic evaluation. As a health economist, Garry is a co-applicant on a number of pragmatic randomised controlled trials in a variety of clinical areas. His role is generally to assess the costs and benefits associated with different interventions, in order to make judgements about cost-effectiveness. Methodological work which Professor Barton has undertaken includes the comparison of two measures of utility (the EQ-5D and SF-6D) which can be used to measure the benefits of interventions, where the practicality, construct validity, and responsiveness of these two measures were assessed.


Environmental and social influences on health

The research led by Andy Jones and his group focusses on the

environmental and social determinants of health outcomes and

health related behaviours. We undertake research to understand

how the context in which people live, work, and study may affect

their health. We have a focus on physical activity and dietary

behaviours but also holder wider health interests, and we are

involved in several population studies which present opportunities

for students wishing to obtain research experience of non-

laboratory analysis. Studying for an MRes with us also provides

great opportunities for undertaking research in collaboration with a

range of organisations outside the academic and health sectors,

such as local authorities, national bodies such as Sport England

and more local providers including Active Norfolk. We also work closely with members of the Medical Research

Council Epidemiology Unit in Cambridge and I also lead the Health Geography programme of the UK Centre of

Excellence in Physical Activity and Dietary Research (CEDAR – http://www.cedar.iph.cam.ac.uk/), both of which

provide students with the potential for experience of working in an internationally recognised collaborative research

environment.

Current projects include:

• Cohort studies on the influences of the environment on physical activity in children, adolescents, and older adults.

• Research on the best ways to increase the prevalence of walking and cycling behaviours.

• Work on health interventions with under-represented groups including those living in material disadvantage or

with disabilities.

• Use of technologies to track people’s use of the environment for health-related behaviours.



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Economics of ageing

My experience and interests centre on the economics of ageing, including long-term care finance, disability benefits for older people, health and disability in later life. My research involves the statistical analysis of large-scale household survey data, particularly through microsimulation/tax-benefit modelling.

Recent research has been aimed at estimating the additional personal costs experienced by older disabled people in order to guide disability benefits policy. Using household survey data on older people’s incomes, material living standards and disability levels, we can infer the extra income than a disabled older person needs to achieve the same standard of living as an otherwise similar non-disabled person. Economists call this extra income (∆ in the graph below) a ‘compensating variation’ – a concept which has a wide range of applications in health economics. Contact: [email protected]

Economic evaluation methods Professor Tracey Sach is a Professor in Health Economics with an interest in developing and applying economic evaluation methods in a number of clinical areas including Dermatology, Falls, and Rehabilitation. For medical student research she can supervise systematic reviews of economic evidence and /or potentially primary data analysis alongside on-going projects of a methodological or applied nature should they be at the right stage at the time.


Public health and clinical intervention

Fujian Song has experience in systematic reviews and simulation modelling for evaluating healthcare interventions, conducted methodological research concerning evidence synthesis, including heterogeneity in meta-analysis, publication and related biases, assessment of non-randomised studies, indirect and mixed treatment comparison for evaluating competing healthcare interventions, and methods for synthesizing evidence for the evaluation of complex healthcare interventions. Current research projects potentially suitable to MBBS students:

Systematic review/meta-analysis of selected public health or clinical interventions and epidemiological studies;

Literature-based methodological research related to clinical trials and research synthesis (e.g., systematic review methods, complex healthcare interventions, indirect comparison, and publication bias);

Evidence based global health.






Addiction research

Dr Caitlin Notley leads the Addiction Research Group: The group produces high quality multidisciplinary research

evidence to impact upon people who are affected by addiction, including service users, carers, health professionals

and policy makers. The research approach emphasises responsiveness to social, cultural and pressing health

needs, and supporting high risk or disadvantaged groups. Caitlin is a social scientist, and an expert in qualitative

research methodologies applied across health and social sciences. She has extensive experience of running

qualitative studies as stand-alone projects or alongside clinical trials,

intervention development and systematic reviewing. Caitlin is a Cochrane

author situated within the Cochrane tobacco and alcohol review group.

Her particular areas of research expertise, that she would welcome

students to work with on, are tobacco smoking cessation, relapse

prevention and electronic cigarette use. She could also supervise projects

more broadly in the fields of substance dependency, misuse and

addiction, alcohol misuse, mental health and young people, health needs

assessment and qualitative systematic reviewing.

Currently Caitlin has projects funded by the National Institute for Health Research, focused on smoking cessation

provision within neonatal intensive care units; Cancer Research UK, focused on dual use of e cigarettes and

tobacco smoking; and Public Health England, on young peoples use of e cigarette flavours. Starting in 2020 Caitlin

will be leading a large scale randomised controlled trial funded by the NIHR to test a smoking relapse prevention

intervention developed through previous work

Relevant Links https://www.uea.ac.uk/medicine/research/addiction Contact: [email protected]

Social gerontology I am a social gerontologist and expert in qualitative research methods. I am interested in promoting improvements to the quality of life and wellbeing of older people by contributing to knowledge and advances in healthy ageing. My areas of interest include: health and social care, sociology of diagnosis, adherence to osteoporosis medicine, physical activity, health literacy and healthcare communication. I also research empathy in the medical consultation. My work involves users and/or patients and public involvement. Current research projects include:

A trial of older people setting personal goals in general practice

https://www.uea.ac.uk/medicine/research/primary-care-and-

epidemiology/goalplan)

A study with Sports England and Active Norfolk on physical activity

at retirement https://www.sportengland.org/funding/active-ageing/

Figure 1: Older women’s experience of taking bisphosphonate medication by

Alice Edwards MED tudent and Brandon Mattless of Norwich University of the

Arts


https://www.uea.ac.uk/medicine/research/addiction


https://www.uea.ac.uk/medicine/research/primary-care-and-epidemiology/goalplan

https://www.uea.ac.uk/medicine/research/primary-care-and-epidemiology/goalplan

https://www.sportengland.org/funding/active-ageing/


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