Host defence peptides and their role in inflammation in the respiratory trace

Lead Research Organisation: University of Edinburgh

Abstract

Death from respiratory disease in the UK is twice the EU average. Illnesses such as lung cancer, asthma, pneumonia and chronic obstructive pulmonary disease are now killing more people in the UK than coronary heart disease. Cystic fibrosis is an inherited condition and results in premature death from lung disease as a result of repeated airway infections. The predominance of multi resistance superbugs makes the illness more difficult to treat and limits the quality of life of affected individuals.||Recently I have identified several naturally occurring small antibiotic molecule that are effective at killing several important superbugs. I wish to understand how this molecule kills bacteria and whether this will help the design of new antibiotics for use in the clinic.||I am also interested in how these host defence peptides are involved in inflammation and what function they have in addition to being antimicrobials.

Technical Summary

Death from respiratory disease in the UK is twice the EU average and is now killing more people in the UK than coronary heart disease. Cystic fibrosis is a genetic disease that results in premature death from lung disease precipitated by chronic microbial infection and inflammation. The predominance of multi resistance superbugs exacerbates the condition and limits the quality of life of affected individuals. ||My research aims to relate genes involved in the innate immune response to the destructive effects of inflammation. In particular I am focussing on ?-defensin genes which are host defence peptides that link the innate and adaptive immune responses. The ?-defensin gene cluster is highly copy number variable and increase or decrease in copy number has been implicated in inflammatory disease including Psoriasis and Crohns disease. In vitro they are both antimicrobial and are chemoattractant for monocytes, CD4+ T cells and immature dendritic cells. I wish to understand the function of these peptides using in vivo models (mice and zebrafish) and to relate structure and function. We hope to use this information to design novel peptides with immunomodulatory activity.

Publications

10 25 50
 
Title transgenic mice 
Description Variety of transgenic mice deleting defensin genes or over expressing them. 5 lines 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2015 
Provided To Others? Yes  
Impact publication and invited as speaker to Gordon Conference on antimicrobial peptides Zhou et al 2013 Plos Genetics Keynote speaker at V1th International conference of epididymis 2015 Semple et al 2015 Plos Genetics 10.1371/journal.pgen.1005673 
 
Description Dunbar Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 6000 members of public attended the science festival in Dunbar and we ran gene genius workshops with taste tests, genetic information and preparation of check cell slides, children making their own cells using balloons. non-stop over Saturday and Sunday.

many participants wanted information on genome sequencing, what can cause various traits in their family. Local grammar school very happy with microscope we donated. uptake in biology reported as very strong.
Year(s) Of Engagement Activity 2014
URL http://2014.dunbarscifest.org.uk/
 
Description dunbar Science festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact workshop cell investigator with cheek slide prep, making a cell balloon, taste test
Year(s) Of Engagement Activity 2015
URL http://dunbarscifest.org.uk/workshops
 
Description edinburgh International Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Amazing Immunology. Workshop including three separate activities based on allergy. I was just helping on one day.
Year(s) Of Engagement Activity 2015
URL http://www.sciencefestival.co.uk/event-details/amazing-immunology-2015