Biography

Lindsay Hall qualified with a BSc (Hons) in Microbiology from the University of Glasgow in 2003. She went on to study for a PhD in Microbiology and Immunology at the Wellcome Trust Sanger Institute under the supervision of Prof Gordon Dougan. Her thesis focused on designing and creating mucosal vaccines against Mycobacterium tuberculosis and characterising mucosal immune responses (specifically Natural Killer, [NK] cells) induced after oral and intranasal immunisations. Her PhD was part funded through the EU sixth framework programme entitled Mucosal Vaccines Against Poverty Related Diseases (MUVAPRED). In 2007 Lindsay took up a postdoctoral position at the Alimentary Pharambiotic Centre, University College Cork in Ireland. During her time in Cork, Lindsay moved into a new mucosal immunology area; focused on intestinal inflammatory disorders. Her research utilised experimental Ulcerative colitis and enteric pathogen models to understand the protective role of early mucosal immune responses (including NK cells) during acute intestinal inflammation. In Cork, Lindsay also started to work on the bacterial communities that inhabit the gut, termed the microbiota. Specifically understanding the role of individual members (i.e. Bifidobacterium) and their products (exopolysaccharide capsules) in modulating the critical commensal-host interaction. She returned to the UK in October 2011 to take up a lecturing and Principle Investigator position within the Norwich Medical School, UEA. With her move to Norwich, Lindsay also took up a Research Leader position at the Institute of Food Research, working within the Gut Health and Food Safety programme. In 2013 Lindsay was awarded a 5 year Wellcome Trust New Investigator Award and is building her research team that studies the role of early life gut microbiota in resistance to enteric (gut) infections. Most recently (August 2014), Lindsay was promoted to senior lecturer in gastrointestinal sciences. 

Career History

2014-current Senior Lecturer and Research Leader in Gastrointestinal Sciences, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich.

2011-current Research Leader, Institute of Food Research, Norwich Research Park, Norwich.

2011-2014 Lecturer and Research Leader in Gastrointestinal Sciences, Norwich Medical School, University East Anglia, Norwich Research Park, Norwich.

2007 – 2011 Post Doctoral Research Fellow, Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork, Cork, Ireland.

2003 – 2007: Ph.D, University of Cambridge. The Wellcome Trust Sanger Institute, Hinxton, Cambridge.

1999 – 2003: BSc (Hons), Microbiology, University of Glasgow.

All Publications

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Forde, P. F., Hall, L., de Kruijf, M., Bourke, M. G., Doddy, T., Sadadcharam, M., Soden, D. M.

(2015)

Non-viral immune electro-gene therapy induces potent anti-tumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models,

in Gene Therapy

22

pp. 29–39

Full Text UEA Repository

(Article)

(Published)


Forde, P. F., Hall, L. J., Sadadcharam, M., de Kruijf, M., O’ Sullivan, G. C., Soden, D. M.

(2014)

Development and characterization of an enhanced nonviral expression vector for electroporation cancer treatment,

in Molecular Therapy — Methods & Clinical Development

1

article no. 14012

Full Text UEA Repository

(Article)

(Published)


Forde, P. F., Sadadcharam, M., Hall, L. J., O'Donovan, T. R., de Kruijf, M., Byrne, W. L., O'Sullivan, G. C., Soden, D. M.

(2014)

Enhancement of electroporation facilitated immunogene therapy via T-reg depletion,

in Cancer Gene Therapy

21

pp. 349-354

Full Text UEA Repository

(Article)

(Published)


Hall, L. J., Walshaw, J., Watson, A. J. M.

(2014)

Gut Microbiome in New-Onset Crohn's Disease,

in Gastroenterology

147

(4)

pp. 932–934

Full Text UEA Repository

(Article)

(Published)


Watson, A., Hall, L.

(2013)

Regulation of host gene expression by gut microbiota,

in Gastroenterology

144

(4)

pp. 841-4

UEA Repository

(Article)

(Published)


Hall, L., Murphy, C., Quinlan, A., Hurley, G., Shanahan, F., Nally, K., Melgar, S.

(2013)

Natural killer cells protect mice from DSS-induced colitis by regulating neutrophil function via the NKG2A receptor,

in Mucosal Immunology

6

pp. 1016-1026

Full Text UEA Repository

(Article)

(Published)


Hall, L., Murphy, C., Hurley, G., Quinlan, A., Shanahan, F., Nally, K., Melgar, S.

(2013)

Natural Killer cells protect against mucosal and systemic infection with the enteric pathogen Citrobacter rodentium,

in Infection and Immunity

81

(2)

pp. 460-469

Full Text UEA Repository

(Article)

(Published)


Williams, J. M., Duckworth, C. A., Watson, A. J. M., Frey, M. R., Miguel, J. C., Burkitt, M. D., Sutton, R., Hughes, K. R., Hall, L. J., Caamaño, J. H., Campbell, B. J., Pritchard, D. M.

(2013)

A mouse model of pathological small intestinal epithelial cell apoptosis and shedding induced by systemic administration of lipopolysaccharide,

in Disease Models & Mechanisms

6

(6)

pp. 1388-1399

Full Text UEA Repository

(Article)

(Published)


Fanning, S., Hall, L., van Sinderen, D.

(2012)

Bifidobacterium breve UCC2003 surface exopolysaccharide production is a beneficial trait mediating commensal-host interaction through immune modulation and pathogen protection.,

in Gut Microbes

3

(5)

pp. 420-5

Full Text UEA Repository

(Article)

(Published)


Fanning, S., Hall, L., Cronin, M., Zomer, A., MacSharry, J., Goulding, D., O'Connell Motherway, M., Shanahan, F., Nally, K., Dougan, G., van Sinderen, D.

(2012)

Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection,

in Proceedings of the National Academy of Sciences

109

(6)

pp. 2108-2113

Full Text UEA Repository

(Article)

(Published)


Hall, L. J., Watson, A. J. M.

(2012)

Role of autophagy in NOD2-induced inflammation in Crohn's disease,

in Gastroenterology

142

(4)

pp. 1032-1034

Full Text UEA Repository

(Article)

(Published)


Murphy, C., Hall, L., Hurley, G., Quinlan, A., MacSharry, J., Shanahan, F., Nally, K., Melgar, S.

(2012)

The Sphingosine-1-Phosphate Analogue FTY720 Impairs Mucosal Immunity and Clearance of the Enteric Pathogen Citrobacter rodentium,

in Infection and Immunity

80

(8)

pp. 2712-2723

Full Text UEA Repository

(Article)

(Published)


Watson, A. J. M., Hall, L. J., Hughes, K. R.

(2012)

Cell shedding: old questions answered,

in Gastroenterology

143

(5)

pp. 1389-1391

Full Text UEA Repository

(Article)

(Published)


Dougan, G., Goulding, D., Hall, L.

(2011)

Live Vaccines and Their Role in Modern Vaccinology,

in Replicating Vaccines: A New Generation.

Springer

pp. 3-14

ISBN 978-3-0346-0276-1

UEA Repository

(Chapter)

(Published)


Jansen, A., Hall, L., Clare, S., Goulding, D., Holt, K., Grant, A., Mastroeni, P., Dougan, G., Kingsley, R.

(2011)

A Salmonella Typhimurium-Typhi genomic chimera: A murine-typphoid model to study Vi polysaccharide capsule function,

in PLoS Pathogens

7

(7)

article no. e1002131

Full Text UEA Repository

(Article)

(Published)


Hall, L., Clare, S., Dougan, G.

(2010)

NK cells influence both innate and adaptive immune responses after mucosal immunization with antigen and mucosal adjuvant,

in Journal of Immunology

184

(8)

pp. 4327-4337

UEA Repository

(Article)

(Published)


Hall, L., Clare, S., Dougan, G.

(2010)

Probing local innate immune responses after mucosal immunisation,

in Journal of Immune Based Therapies and Vaccines

8

(5)

UEA Repository

(Article)

(Published)


Hall, L., Faivre, E., Quinlan, A., Shanahan, F., Nally, K., Melgar, S.

(2010)

Induction and activation of adaptive immune populations during acute and chronic phases of a murine model of experimental colitis,

in Digestive Diseases and Sciences

56

(1)

pp. 79-89

UEA Repository

(Article)

(Published)


Murphy, C., Moloney, G., Hall, L., Quinlan, A., Faivre, E., Casey, P., Shanahan, F., Melgar, S., Nally, K.

(2010)

Use of bioluminescence imaging to track neutrophil migration and its inhibition in experimental colitis,

in Clinical and Experimental Immunology

162

(1)

pp. 188-196

UEA Repository

(Article)

(Published)


Hall, L., Clare, S., Pickard, D., Clark, S., Kelly, D., El Ghany, M., Hale, C., Dietrich, J., Andersen, P., Marsh, P., Dougan, G.

(2009)

Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein,

in Vaccine

27

(49)

pp. 6894-6904

UEA Repository

(Article)

(Published)


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Key Research Interests

Research Themes

  • Microbiota
    • Early life (neonatal) 
    • Probiotics
    • Microbiota-epithelium interactions
  • Natural Killer (NK) Cells
    • Ulcerative colitis
    • Gastroenteritis


Research Activity: Microbiota

Early life microbiota

Our bodies are home to complex microbial communities, termed the microbiota, yet when we are born we are completely sterile. Soon after birth we become colonised by these beneficial bacteria, which shape our immune defence and efficiently limit infection by gut pathogens in a process known as colonisation resistance. However, disturbances in early colonisation events, such as caesarian sections (C-sections) and antibiotic exposure, can lead to increased susceptibility to pathogens, as well as allergic, and chronic inflammatory diseases in later life. Currently, our knowledge of the contribution of specific bacterial species during early life development, and how microbiota disturbances increase susceptibility to gut infection is incomplete. Dr Hall has recently been awarded a Wellcome Trust New Investigator Award which is focused on one of the major early life bacterial groups, bifidobacteria. The aim is to understand how these pioneer bifidobacteria colonise the gut (via their surface molecules; Fig 1) and subsequently modulate critical colonisation resistance, and to understand how early life antibiotic-induced disturbances alter this microbial community, ultimately leading to a breakdown in pathogen protection. Another key goal is to identify bifidobacterial communities that can restore a disturbed early life microbiota back into one able to control gut infection. In order to understand these complex communities we use cutting edge next generation sequencing platforms with collaborators at The Genome Analysis Centre and the Wellcome Trust Sanger Institute to generate data that gives us insights into the species present (16s rRNA, whole genome sequencing) and the differential expression of bacterial genes and their products (metagenomics and RNASeq). Alongside this technology we use simple and complex bacterial culturing systems in tandem with innovative early life models to gain mechanistic insights. Gaining further knowledge about these pioneer bifidobacteria may provide a powerful therapeutic focus in infectious and chronic inflammatory disease settings.



For more information on previous research findings please see newspaper article:
http://www.irishexaminer.com/ireland/health/sugar-coated-bacteria-may-help-in-fight-against-cancer-says-ucc-181338.html


Probiotics

Probiotic treatment strategies represent a powerful opportunity for strategically manipulating the early life microbiota when bacterial assembly is altered or delayed. Early delivery (i.e. premature delivery) and care alter the development of the gut microbiota and can lead to development of serious life-threatening diseases, such as Necrotising Enterocolitis (NEC). Preterm infants are commonly delivered by C-section, and in addition normally require extensive antibiotic treatment which can have a radical effect on the gut microbial community. Currently our knowledge on how probiotic treatments modulate the composition and diversity of the gut microbiota in preterm infants is incomplete. Dr Hall, in collaboration with colleagues across the Norwich Research Park, at the Norfolk and Norwich University Hospital (Drs Walston and Clarke) and The Genome Analysis Centre (Dr Swarbreck), is currently defining and characterising the early life (neonatal) microbiota after probiotic treatment. We are aiming to understand how a probiotic treatment strategy in at-risk preterm neonates alters the gut microbial community and correlate this with disease outcomes. We are also characterising specific members of the early life microbiota for future probiotic treatments. Again we utilise data generated from next generation sequencing platforms and more traditional bacterial culture methodologies to probe these key changes. 


Microbiota-intestinal epithelium interactions

Maintaining a strong physical barrier between the lumen of the gut where our microbiota resides from systemic body sites is critical to host wellbeing. The epithelial cells that line the gut help make up this internal barrier and they also have a key role to play in supporting nutrient and water transport. Disturbances in barrier integrity have been linked to a wide range of chronic inflammatory diseases including Inflammatory Bowel Disease. In collaboration with Prof. Alastair Watson (UEA), we are determining to what extent the microbiota plays in modulating the intestinal barrier via specific epithelial interactions. We are focused on identifying and developing potential probiotic therapies that would provide protection against chronic inflammation.

 

Research Activity: Natural Killer Cells

Ulcerative colitis

Natural Killer (NK) cells are a population of white blood cell i.e. immune cells. Previous studies have shown that NK cells have a critical function in immune surveillance against the development of tumours and viral infection; however more recently several studies have indicated that they may have a role to play in more chronic inflammatory and autoimmune conditions. Ulcerative colitis (UC) is a chronic relapsing and remitting inflammatory condition of the large bowel which is a major health problem in developed countries, including the UK (approx. 1:1000). Although the disease mechanisms of UC are still incompletely understood, previous work indicates a complex interplay of genetic and environmental factors (including the microbiota) with a dysregulated immune response. We have shown in previous work that NK cells are in fact able to provide a protective response during experimental colitis via specific surface receptors (i.e. NKG2A; Fig. 2). We now want to further understand the mechanisms at play behind this protective response in human patients and to determine cellular targets that could provide effective therapies in reducing disease relapse and symptoms. We use a variety of immunology and molecular biology methods including 10-colour flow cytometry, histology, confocal microscopy, inflammation models and RNASeq. 

Gastroenteritis

Bacterial gastroenteritis represent a significant health risk in developing countries and more recently also in western countries (usually from contaminated food). The attachment of the bacteria to the intestinal wall induces an immune response leading to the symptoms of gastroenteritis, including abdominal pain, cramps and diarrhoea. Previous work has indicated that NK cells play a key anti-viral role and also act against some respiratory pathogens, but up until recently no role was known in bacterial gastroenteritis for NK cells. We have recently published work showing that NK cells play a crucial protective role during enteric infection (gastroenteritis) by acting as a ‘global’ controller of the immune response against these types of intestinal pathogens. We have unravelled a novel mechanism to deliver a killer punch to infection-causing bacteria (front cover of the journal Infection and Immunity; Fig. 3). We now plan to follow up and study the mechanisms behind these findings and to test NK cell responses during other types of enteric infection. These further studies will enable us to target specific aspects of the anti-infection NK cell response, which may open up new therapeutic avenues focussed on treatments against bacterial gastroenteritis. For these studies we utilise many of the techniques mentioned above, including infection models. 



For further information please see blog (http://blogs.ifr.ac.uk/ghfs/2013/01/new-role-nk/) and newspaper article (http://www.irishtimes.com/news/health/ucc-team-discovers-tummy-bug-clue-1.1251654)

Collaborators

Prof. Gordon Dougan – Wellcome Trust Sanger Institute
Dr Trevor Lawley - Wellcome Trust Sanger Institute
Prof. Douwe van Sinderen – University College Cork
Dr Declan Soden – Cork Cancer Research Centre
Prof. Andrew Macpherson – University of Bern
Prof. Kathy McCoy – University of Bern
Dr Nadia Guerra – Imperial College London
Dr Francesco Colucci – University of Cambridge
Dr Len Stephens – Babraham Institute
Dr David Bernardo Ordiz – Imperial College London
Including numerous collaborators across Norwich Research Park (NRP)

Teaching Interests

Undergraduate:

Dr Hall currently tutors year 2 MBBS students in the Problem Based Learning programme and she is also a Student Selected Study (SSS) tutor and examiner.

She is also a personal tutor to MBBS students.


Postgraduate:

Dr Hall is supervising one doctoral research student.

External Activities and Indicators of Esteem

  • Dr Hall is also a Research Leader at the Institute of Food Research within the Gut Heath and Food Safety programme (http://www.ifr.ac.uk/GHFS/) where her lab and office are based

Professional Activities

  • Member of Euroglycoforum Research Network
  • Member of American Society of Microbiology
  • Member of Society for General Microbiology
  • Member of Mucosal Immunology
  • Member of British Society of Immunology
  • Member of The Science Advisory Board