A role for the microbiota in the response of skin to ultraviolet radiation?
A role for the microbiota in the response of skin to ultraviolet radiation?
批准号:
BB/V007734/1
负责人:
Catherine O'Neill
金额:
$81.76万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2021
资助国家:
英国
项目状态:
未结题
起止时间:
2021 至 --
中文摘要
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英文摘要
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.
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