Hi Reddit! I’m Dr Laurence Bugeon, Senior Research Scientist at Imperial College London. I study how inflammation is mediated by bad lifestyle habits such as smoking or a bad diet. Ask Me Anything.
In addition to my research interest at Imperial I am a member of one of the Ethical Committee overseeing animal research. In our lab we use zebrafish as a model organism to understand the molecular and cellular mechanisms of inflammation mediated by a bad lifestyle.
For example we seek to understand how cigarette smoke leads to induction of inflammation on the respiratory epithelium, which then drives lung inflammatory diseases.
About inflammatory diseases
Inflammatory diseases of the respiratory system such as asthma and chronic obstructive pulmonary disease are increasing globally and remain poorly understood conditions. Cigarette smoke predisposes the respiratory tissue to a higher incidence of inflammatory disease, but it is becoming increasingly apparent that there is also a need to understand the contributions and interactions between innate immune cells and the epithelial lining of the respiratory system.
The contributions and interactions between innate immune cells and the epithelial lining of the respiratory system are still poorly understood, plus there is a need for the development of new in vivo models to enable generation of new treatments that could help to prevent mucosal inflammatory conditions.
About our research
We have found that zebrafish (Danio rerio) are a relevant model for studying the effect of inflammatory stimuli on a respiratory epithelium, since they mimic the immunopathology involved in respiratory inflammatory diseases of humans.
The zebrafish is a model that offers unique experimental opportunities to study mechanisms of inflammation in vivo as it possess both innate and adaptive immune responses and, like other vertebrates, possess a variety of immune cells.
Using zebrafish, we find that an acute exposure to cigarette smoke extracts induces proinflammatory gene expression in the gills of zebrafish and that a longer term exposure leads to structural changes of the gill tissue. This shows that zebrafish gills provide an alternative model for understanding the molecular mechanisms underlying immunity within a respiratory epithelium.
About animal research
Research involving animals forms an important element of our work, but is not undertaken lightly. To reduce animal work as much as we can, we routinely use zebrafish larvae instead of fully developed fish as they have the same sort of cells but do not feel pain.
We also collaborate with clinician to study human samples from consented patients and volunteers. As the techniques available are getting more sophisticated all the time, we can analyse several parameter on the same animal than ever before – and thus can minimise animal work. However, to measure the responses of immune cells within tissues and their integration with immunity throughout the body, some use of animal model, like zebrafish, is still critical for our research.
My commitment to animal welfare is reflected in my role as member of ethical committees that oversee the animal research activities at Imperial College London to implement and promote the development of best practice in animal research (https://www.imperial.ac.uk/research-and-innovation/about-imperial-research/research-integrity/animal-research/regulation/).
Reference for this research:
Reference: Mucosal inflammation at the respiratory interface: a zebrafish model. Progatzky F, Cook HT, Lamb JR, Bugeon L, Dallman MJ. Am J Physiol Lung Cell Mol Physiol. 2016 Mar 15;310(6):L551-61. doi: 10.1152/ajplung.00323.2015.
Here we have used zebrafish as a model to study the effect of inflammatory stimuli such as Cigarette Smoke on the gill tissue and recapitulated some of the basic features of the pathophysiological responses observed in human.
Other research work done in our lab and its relevant publications:
Induction of innate cytokine responses by respiratory mucosal challenge with R848 in zebrafish, mice, and humans. Progatzky F, Jha A, Wane M, Thwaites RS, Makris S, Shattock RJ, Johansson C, Openshaw PJ, Bugeon L, Hansel TT, Dallman MJ. J Allergy Clin Immunol. 2019 Jul;144(1):342-345.e7. doi: 10.1016/j.jaci.2019.04.003.
We compared live zebrafish, mouse and human stimulation to viral RNA mimic at the respiratory surface in each species to mimic viral infection. We found that zebrafish immune responses were remarkably similar to that measured in human. This demonstrates that we could now use zebrafish to study adjuvants for example.
In vitro and in vivo properties of the bovine antimicrobial peptide, Bactenecin 5. Price RL, Bugeon L, Mostowy S, Makendi C, Wren BW, Williams HD, Willcocks SJ. PLoS One. 2019 Jan 9;14(1):e0210508. doi: 10.1371/journal.pone.
In this study we use zebrafish early embryos to study the effects of an antimicrobial peptide. This is an interesting approach as we could visualise directly how immune cells react to tuberculosis in presence or absence of new compounds that could help fighting the disease.
Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation. Progatzky F, Sangha NJ, Yoshida N, McBrien M, Cheung J, Shia A, Scott J, Marchesi JR, Lamb JR, Bugeon L, Dallman MJ. Nat Commun. 2014 Dec 23;5:5864. doi: 10.1038/
Here we gave zebrafish larvae a diet enriched in cholesterol to study the effects on the vasculature. Unexpectedly we found that there was also an inflammatory response in the gut. The ability to visualise inside the live fish without any invasive methods other than a microscope is very powerful and allows more discoveries in the same animal.
Animal research at Imperial College London: https://www.imperial.ac.uk/research-and-innovation/about-imperial-research/research-integrity/animal-research/ Animal research report 2016/17: http://www.imperial.ac.uk/research-and-innovation/about-imperial-research/research-integrity/animal-research/annual-report/
UPDATE [5PM BST]: Thanks very much everyone for your great questions. Keep them coming! I’ll be checking back in tomorrow as I'd like to answer some more.
And a big thanks to r/IAmA for hosting this AMA!