Professor David Gally

Personal Chair of Microbial Genetics

Biography

Background

My research in a nutshell - My research studies the genetic factors that make specific strains of E. coli a threat to human health as well as those that make strain more susceptible to phage predation in order to predict the most effective phage combinations for therapeutic intervention.  Our basic science studies how the bacteria colonise epithelium in both the gut and urinary tract and then use this information to improve development of interventions.  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 and phage in cattle. 

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 an important research focus of my group for nearly twenty years. I was convenor for three rounds of BBSRC Institute Strategic Programme grants at the Roslin Institute, the most recent on the ‘Control of Infectious Diseases’ in Livestock (2017-2023) and was recently seconded to Food Standards Scotland as their Chief Scientific Advisor from 2020-24.  The group's research is now centred around 'predictive' biology for enteric bacteria pathogen.  Specifically we use genome sequences and 'host of isolation' data to attribute the source and human infection threat of an E. coli or Salmonella Typhimurium isolate.  We have taken a similar machine learning approach to develop predictive phage therapy, so to assign bacteriophage that will be active on any specific E. coli strain based on its genome sequence. We are then testing phage cocktails in relevant in vitro and in vivo conditions, working towards use in the clinic. 

Qualifications

BSc Microbiology, University of Newcastle (I) 1988. 

PhD bacterial cell wall assembly, University of Newcastle 1991

Previous Positions  

1991-92        PostDoctoral Position, University of Michigan, USA

1992-94        PostDoctoral Fellowship, Wake Forest University, USA

1994-98        MRC Career Development Fellowship, University of Newcastle

 

1998-1999       Lecturer in Bacteriology, University of Edinburgh.

1999-2004       DEFRA Senior Research Fellow, University of Edinburgh.

2004-2006       Reader in Molecular Microbiology, University of Edinburgh.

Responsibilities & affiliations

Internal Committees and Responsibilities:

I was leader of the Roslin Institute strategic research programme on ‘control of infectious diseases' of livestock funded by the BBSRC’ (multiple iterations 2012-2023)

I am the Exam Board Chair for the AB2 course

External Committees and Responsibilities:

Chief Scientific Advisor for Food Standards Scotland 2020-2024

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.

Help define food safety research strategy at the BBSRC and joint discussions with other BBSRC institutes;

 

Undergraduate 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

Open to PhD supervision enquiries?

Yes

Areas of interest for supervision

I have successfully supervised over 30 PhD students the majority as the main supervisor as well as a number of MSc student

Current PhD students supervised

Emily Welham

Asim Ullah

David Greig

Vesa Qarkaxhija

Talal Hossain

Past PhD students supervised

Qualified PhD students from the group

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

Sam Wagner

Eliza Wolfson

Alex Corbishley

Geoffrey Mainda

Lauren Cowley

Nur Indah Ahmad

Jolinda Pollock

Eliza Wolfson

Sharif Shaaban

Johanna Elvidge

Nadejda Lupolova

Agata Wawszczyk

Amany Hassan

Marta Campillo Poveda

Kaunda Yamba (Lusaka)

Antonia Chalka

Alba Park De La Torriente

Research summary

Our research has been to understand how E. coli causes disease, and then based on that knowledge develop interventions including vaccines and more recently phage therapy - the killing of bacteria with viruses that predate on them.  We are striving for a 'predictive' understanding of E. coli genomes, so that based on the sequence of any E. coli we can infer where it has come from, its threat to animal or human health, and how to successfully treat it with antibiotics or phage. 

 

Current research interests

Our group aims to understand the main factors that contribute to the threat of severe infection by bacteria such as E. coli and Salmonella. We use genomics and machine learning to predict the source host of an infection as well as the threat level for humans. Under a recent UK Treasury-funded programme entitled, 'Pathogen Surveillance in Agriculture, Food and the Environment (PATH-SAFE) we are working with a large number of partners to develop source attribution for E. coli in Scotland, for example to identify the animal or human origin of E. coli isolated from food products or water samples. In the last five years the 'wet laboratory' research of the group has focused on phage therapy for E. coli infections in humans and animals, in particular: (1) E. coli causing both urinary tract infections (UTI) and bacteraemia in humans and dogs; (2) Shiga toxin-producing E. coli (STEC) in cattle. We are applying machine learning to phage-bacterium interaction data to predict phage that will be active on a strain based only on its genome sequence. We are then investigating phage cocktail treatments in conditions mimicking those found in the host before trialling treatments in the target species. For example, phage interventions for urinary tract infections (UTI) involves testing of phage-bacterium interactions in an artificial urine treatment and an animal model of UTI to get clearance for its use to treat canine and human patience with complex E. coli infections. For STEC, the phage cocktails are developed on tissue cells cultures before testing on ex vivo samples from cattle. The aim here is to have phage feed/drink additives for cattle herds that are colonised with STEC of significant threat to human health.

Past research interests

1. Bacteriophage and virulence of Stx producing E. coli; 2. Machine Learning and phage therapy; 3. Host attribution of bacterial zoonoses using machine learning; 4. Vaccine development; 5. Post-transcriptional gene regulation The main research focus of my group is the pathogenesis of Escherichia coli, in particular those causing urinary tract infections in dogs and humans as well as enterohaemorrhagic E. coli (EHEC) in cattle. We aim to understand the genetic factors that contribute to severity of the infection. 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 another main research area, the development of vaccines to prevent EHEC excretion from cattle. 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 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.

Project activity

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


BBSRC (Lead PI). Defining the physiology of E. coli O157:H7 in cattle to develop phage-based interventions (2023-25). (£481,959)

Dogs Trust (Lead PI). Alignment of sequence-based diagnostics and combinatorial phage therapy for treatment of chronic canine urinary tract infections (2023- 2025). (£185,435).

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).

BBSRC Institute strategic funding: Lead of Roslin Institute BBSRC strategic programme in ‘Control of Infectious Diseases of Livestock’. (2017-2022). 30% of my time. (£8.1M)

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).

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