Award details

A role for the microbiota in the response of skin to ultraviolet radiation?

Reference	BB/V007734/1
Principal Investigator / Supervisor	Professor catherine O'Neill
Co-Investigators / Co-Supervisors	Dr Mark Farrar, Professor Andrew McBain, Professor Lesley Rhodes
Institution	The University of Manchester
Department	School of Biological Sciences
Funding type	Research
Value (£)	641,630
Status	Current
Type	Research Grant
Start date	01/09/2021
End date	31/08/2024
Duration	36 months

Abstract

During the last decade, it has become clear that physiological health depends on the body's relationship with its microbiota. Human skin and its microbiota are unique in that they are regularly exposed to UVR in sunlight. This is the principal cause of most skin cancers, with DNA damage to epidermal cells a key initiator. Direct nuclear absorption of UVR leads to the formation of several DNA photoproducts which if not repaired correctly can lead to UVR signature mutations found in skin cancers. Whilst most UVR-induced DNA damage is repaired quickly, a characteristic feature of UVR-exposed skin is the presence of keratinocytes in the process of apoptosis. This is a key process by which excessively damaged cells are removed from the epidermis, reducing the risk of carcinogenesis. Previously we have shown that more human keratinocytes undergo apoptosis when they are irradiated in the presence of the skin commensal bacterium, Staphylococcus (S.) epidermidis. Treatment of keratinocytes with the cell culture supernatant from irradiated (but not unirradiated) S. epidermidis also induces keratinocyte apoptosis suggesting that members of the skin microbiota produce molecules in response to UVR that alter keratinocyte physiology. In this project we will investigate this further using human skin models and a human volunteer study. We will: 1) Determine whether the presence of the commensal microbiota alters responses (inflammation, apoptosis, DNA damage, proliferation) of human skin to UVR in vivo. 2) Using ex vivo human skin, investigate the effect of S. epidermidis on UVR-induced DNA damage and apoptosis. 3) Using cultured keratinocytes and ex vivo human skin, screen for strains of cutaneous bacteria (in a pre-existing strain bank) that can mitigate UVR-induced DNA damage, and/or promote DNA damage repair. This project will help our industrial partners (WBA and Croda) develop better ways of helping consumers to protect their skin against UVR-induced damage.

Summary

It is now clear that our health depends largely on the microbes that exist in and on our bodies i.e. the microbiome. Skin is no exception and we now know that bacteria living on our skin provide us with many essential functions such as combatting infections and helping to enhance the role of skin as a barrier. The skin and its microbiome are unique in that they are regularly exposed to sunlight. For a long time it has been known that sunlight can damage the DNA of skin cells. DNA damage is associated with 'sunburn' which is perhaps, along with tanning, the most well known response of skin to sunlight. However, even exposure which does not cause a sunburn can be sufficient to damage DNA but usually, the skin cells are able to repair this damage very quickly. However, any damage that is too bad to repair is dealt with by the cells undergoing a process called 'apoptosis' which is a very controlled way of the cells dying. This process is essential to stop cells with damaged DNA from multiplying and is part of the skin's defence against forming tumours. How exposure to sunlight affects our skin microbiome is not really known. However, we have shown that there is a particular bacterium on our skin which promotes apoptosis in skin cells that have been exposed to sunlight. This bacterium does this by producing a molecule in response to sunlight that induces apoptosis in skin cells. This shows that our skin microbiome produces molecules that alter how our skin cells work following sunlight exposure. In this project we will be investigating this more. Our first question is: 'Does the presence of the microbiome affect the sunburn response in humans?'. We will answer this by removing the microbiome (by cleaning with alcohol) from an area of skin in 10 volunteers and then exposing them to several doses of 'simulated sunlight'. We will be looking at how the sunburn develops in areas of skin without the microbiome compared to with the microbiome. We will take a 'biopsy' - a small piece of their skin which has been sunlight exposed and we will perform experiments in the laboratory to determine whether cells in this piece of skin have undergone apoptosis. Successful completion of this work will answer a fundamental question as to the role of the skin microbiome in the sunburn response in humans. Our second question relates to the molecule produced by the bacterium that promotes apoptosis. At present we have data as to its effects in isolated skin cells. We now want to look at this in actual skin. We are able to obtain skin from elective plastic surgery procedures and we have methods already established to keep this skin 'alive' in the laboratory. We will be using this to investigate the effects of the molecule in real human skin. We also aim to purify the molecule from the bacterium and try to identify what it is. We will also be studying how the molecule causes apoptosis in skin cells. Successful completion of this work will shed light on the possible role of bacteria in protecting skin against the multiplication of damaged skin cells. Our final question is: 'Are there other bacteria in the skin microbiome that can protect against DNA damage following exposure to sunlight or promote DNA repair?'. We have already (in a previous project) isolated over 150 types of bacteria from healthy humans. We will be testing these bacteria to find out whether any of them can reduce DNA damage or speed up repair of damaged DNA. Successful completion of this work will identify bacteria that could be used as novel sunscreens or 'after sun' treatments for skin. This project benefits from having Walgreen Boots Alliance (aka 'Boots the Chemist') and Croda PLC (a global leader in the manufacture of speciality chemicals) as project partners. A better understanding of the ways in which the microbiome protects skin against sunlight will be beneficial in helping these project partners develop new ways to help consumers protect their skin.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	Industrial Partnership Award (IPA)

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search