Infections, Immunity and Microbes
 

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Liz Sockett

Professor FRS, Faculty of Medicine & Health Sciences

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Biography

BSc University of Leeds 1983; PhD University College London 1986; Research Associate, University of Illinois 1986-88; Research Associate, University of Oxford 1988-1990. Lecturer (1991-98) University of Nottingham Life Sciences. Lecturer (1998) Snr Lecturer (2001) Reader(2004) Professor (2005), University of Nottingham Institute of Genetics.

Lord Dearing Award 2000, Royal Society BAAS Millennium Award 2000, Society for General Microbiology Peter Wildy Prize 2006, Daiwa-Adrian Prize for Anglo-Japanese Science 2007.

University of Nottingham Student Union's Tutor Oscar 2011 and Research Supervisor Oscar 2013.

Elected Fellow of the American Academy of Microbiology 2017.

Elected Fellow of the Royal Society 2019.

Awarded CBE for Services to Microbiology in the Platinum Jubilee Honours List June 2022

Expertise Summary

Bdellovibrio predatory bacteria- molecular biology and applications.

Teaching Summary

I research friendly predatory bacteria as living antibiotics.

From summer 1991 up until summer 2022 I taught microbiology on undergraduate modules at Nottingham- all with specialisms in bacteriology. I also trained BSc and Master students with the able help of my lab colleagues.

From October 2022 I have reduced my hours and am no longer teaching or taking students in the lab. This is to help me look after my husband who was seriously ill in 2021. It also allows myself and our former lab research staff to write up our projects with the time I have available. I will miss teaching you all after 31 years of it!

I'm very grateful for the kind nominations that were linked to my teaching and student supervision over the years. Thank you students past and present for your enthusiasm and response to my teaching. Thanks in part to you:-

The University kindly awarded me a Lord Dearing Prize for teaching in 2000.

The UK Microbiology Society (SGM) awarded me the Peter Wildy Prize in 2006 for communicating and teaching about microbiology.

The Nottingham Student's Union kindly awarded me a "Tutor Oscar" in 2010-11 in the Category of Best All Rounder.

I was chosen as one of the "100 Heroes of the Students Union" to celebrate its centenary.

I was humbled to be awarded a CBE for services to Microbiology, in the Platinum Jubilee Honours list, in 2022.

I have really enjoyed teaching Nottingham students, and am so proud of all the amazing careers you have gone on to. Its always great when people get in touch with an update. If anyone who studied on LIFE2009 or LIFE3035 modules with me, needs some careers advice, I'm still happy to answer emails and look at applications for jobs or future study. Bacteria will always be amazing on all our lives!

Research Summary

Bdellovibrio bacteriovorus

Our research group studied the predatory delta-Proteobacterium Bdellovibrio bacteriovorus. Bdellovibrio are tiny bacteria that naturally invade and eat the pathogenic bacteria that cause skin ulcer, burn & pressure sore infections in people, whilst not being infectious. Our lab has sadly had to close in November 2023 due to family illness. Iam currently working to complete research papers with my former lab colleagues.

With our multidisciplinary approaches our lab's achievements include:

  • The establishment of a genetic system to manipulate Bdellovibrio showing that flagellar motility, although important for locating prey, is not essential for prey-entry, but that surface pili are.
  • Identification of a group of prey-bacterial genes that are upregulated by Bdellovibrio attack. From these genes, identification of bacterial cell wall modifications key to predation of bacteria have been studied in collaboration with Prof Andrew Lovering at University of Bimrnigham. Those include cyclic di GMP signalling proteins, bacterial cell wall degrading and modifying proteins and adhesive proteins at the predator-prey interface.
  • Establishing that predation by Bdellovibrio works on crops and animal pathogens and is safe, given orally, in animals (chickens) With Dr Rob Atterbury and Dr Laura Hobley.
  • Establishing that Bdellovibrio predation is effective in bodily fluids including serum and begun characterising the immune response of humans to Bdellovibrio.
  • Using a Zebrafish infection model and showing Bdellovibrio predation cures Gram-negative pathogen infections and that the host immune system contributes. In collaboration with Dr Serge Mostowy.

Selected Publications

Bdellovibrio bacteriovorus

Our research group studies the predatory delta-Proteobacterium Bdellovibrio bacteriovorus. Bdellovibrio are tiny bacteria that naturally invade and eat the pathogenic bacteria that cause skin ulcer, burn & pressure sore infections in people, whilst not being infectious. Our long-term goals are to establish Bdellovibrio as a treatment for Gram-negative bacterial infections in humans, and in animals and plants.

With our multidisciplinary approaches our lab's achievements include:

  • The establishment of a genetic system to manipulate Bdellovibrio showing that flagellar motility, although important for locating prey, is not essential for prey-entry, but that surface pili are.
  • Identification of a group of prey-bacterial genes that are upregulated by Bdellovibrio attack. From these genes, identification of bacterial cell wall modifications key to predation of bacteria are studied in collaboration with Dr Andrew Lovering.
  • Establishing that predation by Bdellovibrio works on crops and animal pathogens and is safe, given orally, in animals (chickens).
  • Establishing that Bdellovibrio predation is effective in bodily fluids including serum and begun characterising the immune response of humans to Bdellovibrio.
  • Using a Zebrafish infection model and showing Bdellovibrio predation cures Gram-negative pathogen infections and that the host immune system contributes. In collaboration with Dr Serge Mostowy.

Current projects

Mechanisms of Bacterial Invasion (Wellcome Investigator 2018-2023 Joint with Dr Andrew Lovering, University of Nottingham)

Recent Projects

Hosting Research Fellow Dr Simona Huwiler 2018-2020 on two consecutive Swiss National Science Foundation Fellowship Projects on Exit of Bdellovibrio from Bacterial Prey.

Mechanisms of Bdellovibrio predation

(Funded by BBRSC and The Leverhulme Trust)

Collaboration with Dr Stephan Schuster resulted in publication of the first genome sequence from a predatory bacterium and we determined the predatory transcriptome of genes expressed upon prey attack1. From this we have identified a range of proteins, including peptidoglycan enzymes and pilus components, that are potentially key to the predatory process, and are taking a multi-disciplinary proteomic, ultrastructural and genetic approach to understand their functions, collaborating with structural biologist Dr Andy Lovering at the University of Birmingham and Prof Waldemar Vollmer at Newcastle University.

1. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008599

Bdellovibrio as "living antibiotics"……

(Funded by DARPA)

In response to the emergence of antimicrobial resistance as a global health issue, in addition to the development of new antibiotics, measures are being sort to identify alternatives to antibiotics. One potential approach is the use of living predatory bacteria, such as Bdellovibrio to treat infections, especially those caused by multi-drug resistant pathogens.

….In poultry. Our lab have applied whole Bdellovibrio to combat pathogens in live poultry and food crops. In collaboration with Professor John King we developed a mathematical model of Bdellovibrio predation in the presence of live decoy bacteria, of importance in establishing how Bdellovibrio could be applied as a "living antibiotic"2. In 2011 we published the first experimental trial of Bdellovibrio as an oral treatment for Salmonella in poultry, establishing activity without affecting animal wellbeing3.

….In humans? 4 We are now involved in a project to translate this to pathogens responsible for infections in humans. This is a highly multidisciplinary project, bringing together a team of researchers from microbiology, immunology, computer science and genetics to study Bdellovibrio and its actions on CDC interest pathogens using clinical isolates from the Nottingham University Hospitals NHS Trust. We are firstly testing then in zebrafish models.

We are funded by DARPA, as part of their Pathogen Predators program, to investigate basic science and immunology of this predatory bacterium to underpin future human applications. This program aims to lay the groundwork for tests of a living predator-based therapeutic that we would want to establish as safe and effective against a large number of gram negative infections, including those that are resistant to conventional treatments.

2. http://aem.asm.org/content/72/10/6757.long

3. http://aem.asm.org/content/77/16/5794.long

4. http://onlinelibrary.wiley.com/doi/10.1111/1758-2229.12516/full

Lab members have been actively involved in a number of initiatives and conferences relevant to our research:

Specialist meetings:

Small group meeting to discuss "The Current State of the Antibiotic Pipeline" hosted by The Pew Charitable Trusts, the Wellcome Trust, and the American Society for Microbiology, following publication of "A Scientific Roadmap for Antibiotic Discovery" by The Pew Charitable Trusts, May 2016

http://www.pewtrusts.org/en/research-and-analysis/reports/2016/05/a-scientific-roadmap-for-antibiotic-discovery

University of Nottingham Chancellor's Lecture by Lord O'Neill, Chair of the Review on Antimicrobial Resistance http://www.nottingham.ac.uk/alumni/newseventsandfeatures/events/event-records/chancellors-lecture-series-lord-oneill.aspx

Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)

http://www.jpiamr.eu/

Media and publications:

Pew Charitable Trusts Blog: 'Outside-the-Box' Approaches Can Help Combat Antibiotic Resistance. By Carolyn Shore and Liz Sockett

http://www.pewtrusts.org/en/research-and-analysis/analysis/2017/01/05/out-of-the-box-approaches-can-help-combat-antibiotic-resistance

Crystal Ball 2017- Special Issue Article for Environmental Microbiology Reports

Nature knows best: employing whole microbial strategies to tackle antibiotic resistant pathogens http://onlinelibrary.wiley.com/doi/10.1111/1758-2229.12518/epdf

Public events:

Pre-pint of Science, Nottingham, Feb 2017

Falk Forum 58 - Edinburgh. IBD - The evolution of a disease

Strategy groups:

Bridging the Gaps: Systems-level approaches to antimicrobial resistance

http://www.nottingham.ac.uk/research/groups/bridging/

East Midlands Infectious Disease Research Network (EMIDRN)

Conferences:

Gordon research conference "Microbial Toxins & Pathogenicity"

Gordon research conference "Bacterial Cell Surfaces"

Bacterial Morphogenesis, Survival and Virulence: Regulation in 4D

http://conference.iisertvm.ac.in/bmsv/index.php/welcome

Zebrafish disease model society

http://zdmsociety.org/zdm9/

Media news about our publications:

Injections of Predatory Bacteria Work Alongside Host Immune Cells to Treat Shigella Infection in Zebrafish Larvae

http://www.sciencedirect.com/science/article/pii/S0960982216311526

As featured on the BBC website: http://www.bbc.co.uk/news/health-38077263 and on BBC Radio 4 "Inside Science" http://www.bbc.co.uk/news/health-38106462

Ankyrin-mediated self-protection during cell invasion by the bacterial predator Bdellovibrio bacteriovorus

http://www.nature.com/articles/ncomms9884

Featured on BBC Radio 4 "Inside Science" http://www.bbc.co.uk/programmes/b06s9shs and by BBSRC "How bacterial predators kill other bacteria without harming themselves" http://www.bbsrc.ac.uk/news/health/2015/151202-pr-how-bacterial-predators-kill-other-bacteria/?colour=red&issue=Winter%202016

Current Lab members

Carey Lambert

Rob Till

Jess Tyson

Paul Radford

Luke Ray

Simona Huwiler

Emma Banks

Ting Lai

Callum Clark

Current collaborators

Dr Andrew Lovering, School of Biosciences, University of Birmingham

Dr Serge Mostowy, Centre for Molecular Bacteriology and Infection, Imperial College London.

Dr Mathew Diggle, Strategic & Clinical Lead for Clinical Microbiology, EMPath Pathology Services, Nottingham University Hospitals NHS Trust, Nottingham.

Dr Jamie Twycross, School of Computer Science, University of Nottingham.

Dr Erkin Kuru, Department of Genetics, Harvard Medical School. (Formerly Indiana University)

Professor Yves Brun, Dept of Biology, Indiana University.

Professor Michael VanNieuwenhze, Dept of Chemistry, Indiana University.

Professor Waldemar Vollmer, Newcastle University.

Infections, Immunity and Microbes

School of Life Sciences
University of Nottingham
Medical School
Queen's Medical Centre
Nottingham NG7 2UH