Dr John Worthington
Senior Lecturer in Infection Biology and Part I Director of StudiesResearch Overview
The intestinal epithelium offers the first interaction between commensal bacteria, pathogens and our bodies’ largest immune system. Inappropriate immune responses drive inflammatory bowel disease (IBD) or excessive inflammation during infection. My research focuses on the epithelial enteroendocrine cells (EECs), which release peptide hormones in response to nutrients allowing their efficient digestion. EEC alterations are strongly associated with inflammation, yet the possibility of interactions between our gut’s endocrine and immune systems remains overlooked. Understanding the mechanistic cross-talk between enteroendocrine and immune cells will identify the immunoendocrine axis as a key feature of intestinal health which could be therapeutically targeted during disease.
Research Interests
The intestinal epithelium represents one of the body’s most important interfaces with the external environment, not only as an essential point of detection and absorption of nutrients, but also acting as an efficient barrier against the plethora of toxins and microorganisms we encounter on a daily basis. Indeed, the intestinal epithelium offers the first interaction between pathogens and our body’s defences and as such harbors the major immune system of the body. My research focuses on the often neglected enteroendocrine cells (EECs) of the epithelium, which despite only comprising 1% of the epithelium; collectively form the largest mammalian endocrine system. Regulatory peptides and amines are released from EECs in response to luminal nutrients, and have classically been studied in terms of their role in controlling feeding centres in the brain via stimulation of the vagus nerve. However, the possibility that they play a role in orchestrating the immune response remains largely overlooked. Indeed, recent studies have implicated a role for EECs in innate immunity as they possess functional Toll like receptors and alterations in EEC numbers and secretions are well associated with intestinal infections.
My work focuses on understanding the interactions between our gut’s endocrine and immune systems during homeostasis and inflammation. I utilize intestinal infection models as well as in vitro studies to dissect the mechanistic interaction between these diverse systems to potentially inform new EEC-derived therapeutic strategies for inflammatory diseases of the intestine.
Career Details
After receiving my BSc in Biology from Nottingham University in 2002, I became a Research Technician in Professor Grencis' lab at The University of Manchester. I soon became fascinated with host-parasite interactions of the enteric environment and after completing a short research technician post in endocrinology went on to pursue a PhD in 2004, under the supervision of Professor John McLaughlin. After receiving my PhD in 2008, entitled 'Molecular mechanisms of the gut immune systems and effects on nutrient sensing cells', I joined the lab of Dr Mark Travis in the Wellcome Trust Centre for Cell Matrix Research, examining the role of the integrin avß8 on dendritic cells during infection and autoimmunity. I moved with Mark to the newly established Manchester Collaborative Centre for Inflammation Research in 2012 for a second post-doc, establishing an essential role for avß8 integrin on regulatory T cells during autoimmunity. In 2014, I was awarded a Wellcome Trust funded stepping stones fellowship at Manchester to help establish my own lab, before accepting a lectureship in Infection Biology at Lancaster University in 2016.
External Roles
Honarary Lecturer at the University of Manchester
PhD Supervision Interests
I am happy to accept proposals on projects in the area of intestinal inflammation focussing on parasitology, immunology and endocrinology.
Mechansisms of volatile organic compound detection for whipworm diagnosis
01/10/2024 → 30/09/2026
Research
Volatile organic compound detection of intestinal whipworm infection
27/02/2023 → 26/08/2024
Research
Re-purposing GLP-1 receptor agonists for use as ani-helminth therapy
01/01/2022 → 31/12/2023
Research
Re-purposing GLP-1 receptor agonists for use as ani-helminth therapy
01/01/2022 → 31/12/2023
Research
Tropism, Immunity and Pathology in African sleeping sickness (HAT-TIP)
01/01/2022 → 30/09/2022
Research
Understanding the Mechanisms of antibiotic induced weight loss and subsequent impact on Immunity (Megan Dooley)
01/01/2022 → 31/12/2024
Research
EPSRC Core Equipment 2020
14/11/2020 → 13/05/2022
Research
Dual morbidities in the developing world: The effect of obesity on susceptibility to nematode infection
01/12/2019 → 30/11/2021
Research
Glucagon-like peptide-1; a hormone with a key role in mammalian helminth infection
18/09/2017 → 09/10/2020
Research
McGraw Hill
School Engagement
Parrenthorn high school
School Engagement
Inaugural Event of the Africa Research Hub
Symposium
Grant review
Expert Opinion
Grant Review
Expert Opinion
100 Years, 100 Objects: Stories from the Collections of Lancaster City Museums
Public Lecture/ Debate/Seminar
Mucosal Immunology (Journal)
Publication peer-review
Gut Microbes (Journal)
Publication peer-review
Parasite Immunology (Journal)
Publication peer-review
Immunology (Journal)
Publication peer-review
Carnegie Research Assessor
Expert Opinion
British Society for Immunolgy Annual Congress
Oral presentation
FIOCRUZ
School Engagement
FluWHo
Public Lecture/ Debate/Seminar
Immune-endocrine interactions at the gut barrier
Invited talk
Immune-endocrine interactions at the gut barrier for novel therapeutics
Invited talk
Grant Review
Expert Opinion
PLoS Pathogens (Journal)
Publication peer-review
Gut Microbes (Journal)
Publication peer-review
Grant Review
Expert Opinion
Mucosal Immunology (Journal)
Publication peer-review
Parasite Immunology (Journal)
Publication peer-review
Frontiers in Immunology (Journal)
Publication peer-review
writing your next grant application
Public Lecture/ Debate/Seminar
Covid-the unanswered questions
Public Lecture/ Debate/Seminar
British Society for Immunology Congress 2019
Participation in conference -Mixed Audience
British Society for Immunology Congress 2019
Participation in conference -Mixed Audience
- Cancer Biology and Genome Stability
- Microbes, Pathogens and Immunity