Harnessing the health-associated dermal microbiota for improving skin health.
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
The human body is associated with trillions of bacteria, which exist as sessile communities on and within tissues; principally the skin and the digestive tract. The balance of the microbial communities that comprise the human microbiome (or microbiota) is crucial to human health, yet relatively little is known about how bacterial species
interact with each other and with host cells within defined tissue niches in human health. Ageing is associated with imbalances in microbiome composition (dysbiosis) and reduced bacterial diversity. Maintaining a balanced microbiota is therefore important for our health. Our previous work indicates that changes in the populations of
bacteria within skin tissue niches are associated with inflammation and delayed wound healing. Specifically we have defined bacterial populations within the normal dermal microbiota that, independent of infection, are associated with skin healing (Stenotrophomonas and Brevibacterium) or delayed healing and excessive inflammation
(Pseudomonas aeruginosa, Peptoniphilus, Anaearococcus spp., Finegoldia and Staphylococcus aureus). Putatively commensal bacteria such as S. epidermidis are usually beneficial commensals but in certain conditions can cause inflammation thus we will also investigate their interactions with the host.
The aim of the proposed project is to define how an array of numerally important skin bacteria affect host cell function, with a major focus on defining the nature of bacterial interactions with epithelial cells (keratinocytes) and immune cells (macrophages) using in vitro and ex vivo models. Bacteria have been shown to drive proliferation and cell death of keratinocytes as well as change barrier properties (e.g. tight junction integrity). Therefore, we will analyse cell death, proliferation and barrier integrity. We will also assess epithelial cytokine production in response to bacteria. as our previous work has suggested that different bacteria can drive discrete cytokine responses.
Bacteria can drive the activation and differentiation of macrophages thus we investigate macrophage polarisation, phagocytosis, cell surface phenotype and cytokine production. Techniques will include flow cytometry, qPCR, RNAseq and microscopy. The project will also investigate the potential of candidate probiotic bacteria to rescue
damaging effects caused by pro-inflammatory bacteria since we previously showed that probiotics rescue keratinocytes from the toxic effects of S. aureus. The project will take advantage of the multidisciplinary supervisory team with expertise in microbiology, immunology, cell biology and omics analysis to dissect the nature of microbial interaction and in health and susceptibility to inflammation. All protocols are well established in the host laboratories. This project is a partnership with SkinBioTherapeutics PLC.
interact with each other and with host cells within defined tissue niches in human health. Ageing is associated with imbalances in microbiome composition (dysbiosis) and reduced bacterial diversity. Maintaining a balanced microbiota is therefore important for our health. Our previous work indicates that changes in the populations of
bacteria within skin tissue niches are associated with inflammation and delayed wound healing. Specifically we have defined bacterial populations within the normal dermal microbiota that, independent of infection, are associated with skin healing (Stenotrophomonas and Brevibacterium) or delayed healing and excessive inflammation
(Pseudomonas aeruginosa, Peptoniphilus, Anaearococcus spp., Finegoldia and Staphylococcus aureus). Putatively commensal bacteria such as S. epidermidis are usually beneficial commensals but in certain conditions can cause inflammation thus we will also investigate their interactions with the host.
The aim of the proposed project is to define how an array of numerally important skin bacteria affect host cell function, with a major focus on defining the nature of bacterial interactions with epithelial cells (keratinocytes) and immune cells (macrophages) using in vitro and ex vivo models. Bacteria have been shown to drive proliferation and cell death of keratinocytes as well as change barrier properties (e.g. tight junction integrity). Therefore, we will analyse cell death, proliferation and barrier integrity. We will also assess epithelial cytokine production in response to bacteria. as our previous work has suggested that different bacteria can drive discrete cytokine responses.
Bacteria can drive the activation and differentiation of macrophages thus we investigate macrophage polarisation, phagocytosis, cell surface phenotype and cytokine production. Techniques will include flow cytometry, qPCR, RNAseq and microscopy. The project will also investigate the potential of candidate probiotic bacteria to rescue
damaging effects caused by pro-inflammatory bacteria since we previously showed that probiotics rescue keratinocytes from the toxic effects of S. aureus. The project will take advantage of the multidisciplinary supervisory team with expertise in microbiology, immunology, cell biology and omics analysis to dissect the nature of microbial interaction and in health and susceptibility to inflammation. All protocols are well established in the host laboratories. This project is a partnership with SkinBioTherapeutics PLC.
