David Gally

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Personal profile

Current Research Interests

My research aims to define the genetic determinants that contribute to the spread of important zoonotic diseases such as those caused by enterohaemorrhagic E. coli and Salmonella.  Current work is applying machine learning and phylogenomics to predict the source and disease threat of isolates. Similar approaches are now being applied to phage therapy. The other main focus of our research is to understand the expression of bacterial colonisation factors and apply this knowledge to develop vaccines to limit bacterial zoonotic diseases. 

Research Interests

  • Bacteriophage and virulence of Stx producing E. coli
  • Machine Learning and phage therapy
  • Host attribution of bacterial zoonoses using machine learning
  • Vaccine development
  • Post-transcriptional gene regulation

The main research focus of my group is the pathogenesis of Escherichia coli, in particular zoonoses caused by enterohaemorrhagic E. coli (EHEC).  We study the colonization of cattle by EHEC strains and aim to understand the genetic factors that lead to infections in humans.  Specifically, our recent work is making use of whole genome sequencing to define the subset of animal strains that are a threat to human health.  By analyzing the accessory genome content of both human and cattle strains we are able to predict the strains more likely to cause serious human disease.  This work can then be combined with our other main research area, the development of vaccines to prevent EHEC excretion from cattle.  Our vaccine research has been built on our studies of surface organelle expression in Escherichia coli, in particular of flagella and type III secretion systems.   As we are now able to predict which farms carry strain with a high zoonotic threat then targeted interventions are possible. Roslin Technologies Ltd have recently licenced the IP for the vaccine and are testing the vaccine in a feedlot trial in the USA.  We are also developing flagellin-based fusions for stimulation of mucosal immunity.  The vaccine and adjuvant work is in partnership with Dr Tom McNeilly as the Moredun Research Institute.  We have just completed a two million pound EHEC research programme funded by Food Standards Scotland and the Food Standards Agency that studied the epidemiology and molecular biology of EHEC strains across the UK in partnership with researchers at: the Universities of Glasgow and Edinburgh; the Scottish E. coli Reference Laboratory (SERL); the Moredun Research Institute (MRI); Scotland’s Rural College (SRUC); Public Health Scotland; Public Health England; USDA and University of Brisbane.

At a fundamental level we study how key factors such as Shiga toxins are expressed during infection and how bacteriophage variation and integration into the E. coli genome impact on isolate virulence and their capacity to colonise and be excreted from animal hosts.  This includes control by small RNA molecules expressed from integrated prophages.   We also have three projects focused on antimicrobial resistance in E. coli.  Two of these are using sequencing and bioinformatic approaches to examine the genetic context of resistance genes, especially on plasmids and how acquisition of these leads to other changes in the bacterial cell.  A recently awarded NERC project aims to quantify how antibiotic use on a commercial pig farm alters the copy number of specific resistance genes in animals and the local environment, where the concept is to consider the resistance genes as pollutants that need to be monitored and controlled.

We also now have two main projects focused on new approaches to advance phage therapy: one targeting E. coli urinary tract infections in dogs funded by The Dogs Trust and the second a NIFA-USDA funded project using bacteriophage cocktails to limit E. coli O157 colonisation in cattle. 

The group therefore uses a wide-range of techniques with expertise in genetic manipulation and we encourage applications from individuals interested in PhD or MSc positions. 

Administrative Roles

Internal Committees and Responsibilities:

I am leader of the Roslin Institute strategic research programme on ‘control of infectious diseases' of livestock funded by the BBSRC’.

I was acting Head of Division (April 2016 to July 2016)

I am the Exam Board Chair for the AB2 course

External Committees and Responsibilities:

Invited by MRC and Foreign office to China (Nov 2015) and India (Feb 2016) to describe UK antimicrobial resistance (AMR) research at livestock-human interface.

Veterinary Schools Council: AMR group representative.

NERC grant review panel AMR3.

Workshops to define food safety research strategy at the BBSRC (2017-20) and joint discussions with other BBSRC institutes;

I attended a ‘Microbes in the Food Chain’ workshop at the IFR (now Quadram) May 2017 to help ensure collaboration and represent Roslin’s research interests.

Invited speaker at conferences and universities (>15) over last 5 years.

Teaching

As a member of the R(D)SVS I teach the undergraduate veterinary students basic aspects of ‘Infection and Immunity’, focusing on bacteriology. This includes diagnostic bacteriology practicals.

I provide lectures to the 3rd and 4th years of the Infectious Diseases course

I am Exam Board Chair for Animal Body 2



My research in a nutshell

My research studies the genetic factors that make specific strains of E. coli a threat to human health.  In particular we study strains of E. coli that come from cattle, in which they cause no disease, but can cause bloody diarrhea and sometimes fatal systemic infection if they infect humans.  We try to define and predict which strains represent the most serious threat to human health and aim to eradicate these by using vaccines in cattle.  Our basic science studies how the bacteria colonise cattle and cause damage in humans with this information improving intervention development and how these are targeted. 

Biography

I hold a personal chair in Microbial Genetics at the University of Edinburgh and have been part of the Roslin Institute since 2011.  My background is in Microbiology, initially bacterial physiology for my PhD and first Post Doctoral position at the University of Michigan (cell wall assembly) but I then moved into gene regulation during a second Post Doctoral post in North Carolina and then returned to the UK supported by an MRC Career Development Fellowship which was focused on the regulation of fimbrial adhesins in E. coli.  I obtained a Lectureship in Bacteriology at Edinburgh Vet School in 1998 which soon led to a DEFRA Veterinary Fellowship on the biology of enterohaemorrhagic E. coli (EHEC) which has remained the main research focus of my group for nearly twenty years. We study the colonization of cattle by EHEC strains and aim to understand the genetic factors that lead to effective transmission between animals and infection in humans.  Specifically, our recent work is making use of whole genome sequencing to define the subset of animal strains that are a zoonotic threat to human health.  By analyzing the genome content of both human and cattle strains we are able to predict the strains more likely to cause serious human disease and ongoing work is using machine-learning methods to do this. In partnership with researchers at the Universities of Glasgow and Edinburgh; the Scottish E. coli Reference Laboratory (SERL); the Moredun Research Institute (MRI); Scotland’s Rural College (SRUC); Public Health Scotland; Public Health England and the USDA, we are studying the epidemiology and molecular biology of EHEC strains across the UK and are developing a vaccine to limit the spread of EHEC from cattle to humans. I now lead a BBSRC Institute Strategic Programme on the ‘Control of Infectious Diseases’ in Livestock (2017-2022) at the Roslin Institute and have broadened my research focus to include alternative approaches to the spectre of antimicrobial resistance, including using machine learning to select phage cocktails for personalised phage therapy.

Qualifications

Completed Theses section:

Sally Keegan

Arvind Mahajan

Stuart Naylor

Makrina Totsika

Dai Wang

Alan McNally

Tracy Rosser

James Emmerson

Allen Flockhart

Pablo Nart

Kirsty Smith

Jianing Bai (not UoE)

Amin Tahoun

Xuefang Xu

Indah Ahmad

Eliza Wolfson

Alex Corbishley

Geoffrey Mainda

Lauren Cowley

Jolinda Pollock

Sam Wagner

Amy Beckett (MRI)

Sharif Shaaban

Nadejda Lupolova

 

Current PhD Students

Agata Wawszczyk

Amany Hassan

Marta Campillo Poveda

Alba Park de la Torriente

David Greig

Antonia (Annita) Chalka

 

Major grants awarded (Principle investigator – PI; Co-applicant - CA)


NIFA-USDA. Precision bacteriophage identification through machine learning for mitigating persistent colonization of Shiga toxin-producing Escherichia coli O157:H7 in cattle. (2021-22) Final amount pending.

Dogs Trust (Lead PI). Advanced phage therapy for multidrug resistant E. coliassociated with canine urinary tract infections”: (2020- 2022). (£162,630).

Food Standards Agency Programme (PI). ‘EHEC O157 super-shedding from cattle and the mitigation of human risk’. Collaboration with MRI, SRUK (SAC commercial), University of Glasgow, the Scottish E. coli reference laboratory, Public Health England, and 2 international groups. Value £2,036,140.  Jan. 2014 to Aug. 2017.

NERC. The dynamics of antimicrobial resistance gene prevalence on a commercial pig farm: implications for policy. (CA). Value £160,000. July 2016-June 2018.

BBSRC Impact Acceleration Award (PI). Food safety vaccine strain development. Nov. 2015-Aug.2016. £19,259.

BBSRC International Partnering Award (Argentina) on EHEC human infections. (PI). April 2014-Mar. 2018. £12,900.

BBSRC grant (PI). Defining the molecular basis of H7 flagellin and as an adhesin and mucosal adjuvant for vaccine development. Industrial partnership award with Novartis Animal Health (now Elanco). May 2011-Sept 2014 (extended). £798,000. Lead PI with Dr Arvind Mahajan (UoE) and Prof David Smith and Dr Tom McNeilly (MRI).

Commonwealth Studentship (PI). Molecular epidemiology of antimicrobial resistance (AMR) and Shiga toxigenic E. coli (STEC) in dairy herds of central Zambia. October 2012-Jan 2016.

Wellcome Trust Re-entry Fellowship. Host laboratory for Dr Deborah Hoyle’s WT Fellowship and joint supervision of a technician. July 2015-June 2019.

BBSRC-Zoetis studentship (CA). Analysis of canine MDR strains by SMRT sequencing Oct. 2012-Sept 2016.

A Wellcome Trust research grant. The regulation of type III secretion in enterohaemorrhagic Escherichia coli O157:H7. Hfq-dependent regulation by sRNAs. May 2010 to July 2013. £314,196. Lead PI with Prof. David Tollervey, WT Centre for Cell Biology, UoE.

DEFRA Veterinary Training and Research Award (VTRI). Integration of functional genomics and immunology and their application to infectious disease in ruminants. Sept. 2004 – Aug. 2009 (CA).

LINK grant: DEFRA with Novartis Animal Vaccines Ltd (PI). Vaccination strategies for control of enterohaemorrhagic E. coli O157:H7 in cattle. Nov. 2005-Oct 2008.

FSA grant with SAC (CA). Detection of Sorbitol-fermenting E. coli O157 strains. Nov 2007 – April 2009.

Wellcome Trust research grant (PI): The regulation of virulence loci in enteropathogenic Escherichia coli by PerA, B and C. June 2002 - May 2007 (ext).

Department for Environment, Food and Rural Affairs (DEFRA). Escherichia coli interventions and control. June 2003 – Mar. 2007 (ext). (CA).

Wellcome Trust research grant: Cross-talk between adhesin gene clusters in uropathogenic Escherichia coli. March 2003 - August 2006 (ext). (PI).

BBSRC research grant. The molecular basis to Escherichia coli O157:H7 colonisation of the terminal rectum in cattle. Dec. 2003 – Nov. 2006. (PI).

Department of Environment Food and Rural Affairs (DEFRA) Veterinary Research Fellowship in Microbiology/Pathology, Oct. 1999 – Sept. 2004. (PI).

Scottish Higher Education Funding Council refurbishment and equipment costs with the DEFRA Fellowship. (PI).

BBSRC research grant: analysis of novel adhesin gene clusters in Escherichia coli O157. January 2002 – May 2005 (ext). (PI).

Research funded by Novartis Animal Vaccines Ltd towards vaccine development against enterohaemorrhagic E. coli O157:H7. April 2003 – March 2005. (PI).

BBSRC research grant: cross-regulation between adhesin gene clusters in Escherichia coli. May 1999 – April 2002. (PI).

Education/Academic qualification

Doctor of Philosophy (PhD), Newcastle University

19881991

Award Date: 1 Dec 1991

First class honours degree in Microbiology, Bachelor of Science, Newcastle University

19851988

Award Date: 1 Jun 1988

External positions

Professor of Microbial Genetics, Centre for Infectious Diseases, Chancellor’s Building, University of Edinburgh

2006 → …

Reader in Molecular Microbiology, University of Edinburgh

20042006

DEFRA Senior Research Fellow in Microbiology/Pathology, Division of Veterinary Pathology, Teviot Place, Edinburgh, EH8 9AG

19992004

Lecturer in Bacteriology, Department of Veterinary Pathology, The University of Edinburgh, Summerhall, Edinburgh, EH9 1QH

19981999

Visiting research Fellow for six months, Institute for the Molecular Biology of Infectious Disease, Würzburg, Germany

Jun 1996

Medical Research Council Career Development Fellow, 'Pathogenesis of Escherichia coli: regulation of bacterial adhesion.', Newcastle University

19941998

Postdoctoral Research Fellow, 'Analysis of environmental and genetic factors controlling phase variation of type 1 fimbriae in Escherichia coli.', Department of Microbiology and Immunology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA

19921994

Postdoctoral Research Fellow, 'A study of macromolecular synthetic events during the division cycle of Gram negative bacteria.', Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA

19911992

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