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Understanding bacteria and immune cells in EB Skin to improve treatment options

 

Grant Title: Characterisation of the skin microbiome and investigation of neutrophil function in Epidermolysis Bullosa patients.

Investigator: Professor Iain Chapple

Co-investigators: Dr. Sarah Kuehne, Dr. Josefine Hirschfeld, Dr. Melissa M Grant & Dr. Adrian Heagerty

Institution: Birmingham Dental School and Hospital
Start Date: Q1 2018                  End Date: Q4 2020                   Duration: 3 years

Grant amount: £296,289

Lay Summary

What is being investigated?

This research will investigate the different bacteria that are present on the skin of people with Epidermolysis Bullosa (EB). The human body has twice the number of bacterial cells compared with human cells hence we are actually a complex mix of human and bacterial elements, and health requires our immune system to live in harmony with our bacteria. Most of these bacteria are friendly. However, in EB wounds, bacteria may change and cause infections, delay wound healing, resulting in scarring. Currently, the bacteria living on the skin of people with EB are not well known. This group plan to investigate which bacteria are present in the skin of people with EB and how they behave.

Why is this being investigated?

The human body has specialized immune cells to protect it against infections. Their role is to locate and destroy any foreign cells or bacteria that can make us unwell. In health, we have health-promoting bacteria, that live quite happily with our immune system, however, if the environment changes (by for example trauma that causes a blister), different bacteria can start to grow and this can also upset our immune system. In some diseases, when this happens, the immune cells do not function as they should and can over-react to certain bacteria, in a way that also damages our tissues and can delay wound healing.

Why is this important?

This research is key to understanding whether particular immune cells, called neutrophils, work properly in Epidermolysis Bullosa (EB). Many people affected by EB often suffer from a range of infections and this is a hint that their immune system may not be working efficiently. Investigation of how neutrophils work may provide evidence to design treatment options that can improve their ability to clear disruptive bacteria, allowing the healthy bacteria to come back and re-establish that important balance between our “healthy” bacteria and our immune system.

These two aspects will be studied because in other diseases it is known that bacteria and the immune responses to them are closely linked. Both bacteria and immune cells release signals that influence skin healing, which can cause harm to the skin and can make us more susceptible to other infections. There will also be signals or “molecular” messages that help to heal the skin and a better understanding of these will facilitate development of treatments that stop the harmful signals but enhance the helpful ones. By bringing these areas of research together, we hope to advance the development of effective treatment options for wound healing in people with EB in the future.

Investigator Biography

Iain Chapple

Iain Chapple is Professor of Periodontology and Head of the School of Dentistry at the University of Birmingham UK and Consultant in Restorative Dentistry. He leads a strong team as part of Birmingham’s Periodontal Research Group, and is Director of Research for the Institute of Clinical Sciences at the University of Birmingham. Iain runs a national clinical oral and dental service for adult EB patients in close collaboration with Dr Adrian Heagerty, a Consultant Dermatologist and EB expert. Iain was awarded the Charles Tomes medal by the Royal College of Surgeons in 2012 for his research and also the International Association of Dental Research Distinguished Scientist for Periodontal Research in 2018.

“We are extremely excited by the DEBRA funding for this project, especially given the strong support and interest from our EB patients and delegates at the DEBRA weekend conference. This will enable us to answer fundamental questions about what bacteria live on the skin and colonise wounds, and what effect they may have on how our immune system responds to them and affects how blister sites heal. Ultimately, we hope this will help in the future to develop new approaches to therapy.”