George Birchenough Group
Short description
George Birchenough, PhD, Associated Senior Lecturer in molecular medicine with a focus on Goblet Cells, Mucus & Mucosal Defence.
Goblet cell-mediated mucosal defence
Our mucosal surfaces are the interface between the environment and our tissues. Their physiological functions necessitate constant exposure of living cells to a vast collection of microbial lifeforms that includes many opportunistic and obligate pathogens.
The epithelial cell layer strictly controls interactions between this environment and our internal systemic tissues. However, this single layer of cells can only endure in this setting due to the multi-layered defensive functions of the epithelial cellular lineages.
Goblet cells are a lineage that specialise in the synthesis and secretion of gel-forming mucins and other mucus components that restrict microbial access to the epithelium. Historically considered a single cell type with only this function, recent research hints that they comprise multiple, functionally diverse subpopulations that contribute to different aspects of mucosal defence, thereby regulating our interactions with the mucosal environment.
In collaboration with the wider Mucin Biology Groups cluster at the University of Gothenburg and both national and international partners, the laboratory seeks to develop new tools allowing the identification and characterisation of goblet cell-mediated defence systems.
Our goal is to understand their roles in the pathoaetiology of mucosal-related diseases including enteric infections, inflammatory bowel disease, pre-term birth and diabetes, with the ultimate purpose of developing innovative prophylactic and therapeutic strategies.
Contact Information
george.birchenough@gu.se
Department of Medical Biochemistry and Cell biology
Visiting address:
Medicinaregatan 9 a
41390 Göteborg
Postal address:
Box 440
40530 Göteborg
Birchenough Lab Website
Publications
van der Post S, Jabbar KS, Birchenough G, Arike L, Akhtar N, Sjovall H, Johansson MEV, Hansson GC. Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut. 2019 Dec;68(12):2142-2151. doi: 10.1136/gutjnl-2018-317571. Epub 2019 Mar 26. PubMed PMID: 30914450; PubMed Central PMCID: PMC6872445.
Volk JK, Nyström EEL, van der Post S, Abad BM, Schroeder BO, Johansson Å, Svensson F, Jäverfelt S, Johansson MEV, Hansson GC, Birchenough GMH. The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function. J Exp Med. 2019 Nov 4;216(11):2602-2618. doi: 10.1084/jem.20190679. Epub 2019 Aug 16. PubMed PMID: 31420376; PubMed Central PMCID: PMC6829596.
McCarthy AJ, Birchenough GMH, Taylor PW. Loss of Trefoil Factor 2 Sensitizes Rat Pups to Systemic Infection with the Neonatal Pathogen Escherichia coli K1. Infect Immun. 2019 Mar;87(5). doi: 10.1128/IAI.00878-18. Print 2019 Mar. PubMed PMID: 30833331; PubMed Central PMCID: PMC6479038.
Birchenough G, Schroeder BO, Bäckhed F, Hansson GC. Dietary destabilisation of the balance between the microbiota and the colonic mucus barrier. Gut Microbes. 2019;10(2):246-250. doi: 10.1080/19490976.2018.1513765. Epub 2018 Sep 25. PubMed PMID: 30252606; PubMed Central PMCID: PMC6546334.
Nyström EEL, Birchenough GMH, van der Post S, Arike L, Gruber AD, Hansson GC, Johansson MEV. Calcium-activated Chloride Channel Regulator 1 (CLCA1) Controls Mucus Expansion in Colon by Proteolytic Activity. EBioMedicine. 2018 Jul;33:134-143. doi: 10.1016/j.ebiom.2018.05.031. Epub 2018 Jun 7. PubMed PMID: 29885864; PubMed Central PMCID: PMC6085540.
Schroeder BO, Birchenough GMH, Ståhlman M, Arike L, Johansson MEV, Hansson GC, Bäckhed F. Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration. Cell Host Microbe. 2018 Jan 10;23(1):27-40.e7. doi: 10.1016/j.chom.2017.11.004. Epub 2017 Dec 21. PubMed PMID: 29276171; PubMed Central PMCID: PMC5764785.
Birchenough G, Hansson GC. Bacteria Tell Us How to Protect Our Intestine. Cell Host Microbe. 2017 Jul 12;22(1):3-4. doi: 10.1016/j.chom.2017.06.011. PubMed PMID: 28704650.
Bosmans JW, Jongen AC, Birchenough GM, Nyström EE, Gijbels MJ, Derikx JP, Bouvy ND, Hansson GC. Functional mucous layer and healing of proximal colonic anastomoses in an experimental model. Br J Surg. 2017 Apr;104(5):619-630. doi: 10.1002/bjs.10456. Epub 2017 Feb 13. PubMed PMID: 28195642.
Birchenough GM*, Dalgakiran F*, Witcomb LA, Johansson ME, McCarthy AJ, Hansson GC, Taylor PW. Postnatal development of the small intestinal mucosa drives age-dependent, regio-selective susceptibility to Escherichia coli K1 infection. Sci Rep. 2017 Mar 6;7(1):83. doi: 10.1038/s41598-017-00123-w. PubMed PMID: 28250440; PubMed Central PMCID: PMC5427930. (* shared first author)
Bergström JH*, Birchenough GM*, Katona G, Schroeder BO, Schütte A, Ermund A, Johansson ME, Hansson GC. Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16. Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13833-13838. doi: 10.1073/pnas.1611400113. Epub 2016 Nov 14. PubMed PMID: 27849619; PubMed Central PMCID: PMC5137749. (* shared first author)
Birchenough GM, Nyström EE, Johansson ME, Hansson GC. A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science. 2016 Jun 24;352(6293):1535-42. doi: 10.1126/science.aaf7419. PubMed PMID: 27339979; PubMed Central PMCID: PMC5148821.
Erickson NA, Nyström EE, Mundhenk L, Arike L, Glauben R, Heimesaat MM, Fischer A, Bereswill S, Birchenough GM, Gruber AD, Johansson ME. The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS-Challenged Mice. PLoS One. 2015;10(7):e0131991. doi: 10.1371/journal.pone.0131991. eCollection 2015. PubMed PMID: 26162072; PubMed Central PMCID: PMC4498832.
Birchenough GM, Johansson ME, Gustafsson JK, Bergström JH, Hansson GC. New developments in goblet cell mucus secretion and function. Mucosal Immunol. 2015 Jul;8(4):712-9. doi: 10.1038/mi.2015.32. Epub 2015 Apr 15. Review. PubMed PMID: 25872481; PubMed Central PMCID: PMC4631840.
Dalgakiran F, Witcomb LA, McCarthy AJ, Birchenough GM, Taylor PW. Non-invasive model of neuropathogenic Escherichia coli infection in the neonatal rat. J Vis Exp. 2014 Oct 29;(92):e52018. doi: 10.3791/52018. PubMed PMID: 25408299; PubMed Central PMCID: PMC4353393.
Pelaseyed T, Bergström JH, Gustafsson JK, Ermund A, Birchenough GM, Schütte A, van der Post S, Svensson F, Rodríguez-Piñeiro AM, Nyström EE, Wising C, Johansson ME, Hansson GC. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 2014 Jul;260(1):8-20. doi: 10.1111/imr.12182. Review. PubMed PMID: 24942678; PubMed Central PMCID: PMC4281373.
Birchenough GM, Johansson ME, Stabler RA, Dalgakiran F, Hansson GC, Wren BW, Luzio JP, Taylor PW. Altered innate defenses in the neonatal gastrointestinal tract in response to colonization by neuropathogenic Escherichia coli. Infect Immun. 2013 Sep;81(9):3264-75. doi: 10.1128/IAI.00268-13. Epub 2013 Jun 24. PubMed PMID: 23798529; PubMed Central PMCID: PMC3754193.
Dawson LF, Valiente E, Donahue EH, Birchenough G, Wren BW. Hypervirulent Clostridium difficile PCR-ribotypes exhibit resistance to widely used disinfectants. PLoS One. 2011;6(10):e25754. doi: 10.1371/journal.pone.0025754. Epub 2011 Oct 25. PubMed PMID: 22039420; PubMed Central PMCID: PMC3201945.
Zelmer A, Martin MJ, Gundogdu O, Birchenough G, Lever R, Wren BW, Luzio JP, Taylor PW. Administration of capsule-selective endosialidase E minimizes upregulation of organ gene expression induced by experimental systemic infection with Escherichia coli K1. Microbiology. 2010 Jul;156(Pt 7):2205-2215. doi: 10.1099/mic.0.036145-0. Epub 2010 Apr 15. PubMed PMID: 20395269; PubMed Central PMCID: PMC2923034.
