Activation of the Inflammasome in Skin by Malassezia fungal species
Lead Research Organisation:
University of Glasgow
Department Name: College of Medical, Veterinary, Life Sci
Abstract
Studentship strategic priority area:Basic Bioscience Underpinning Heath
Keywords: Inflammasome Dermatitis Innate Immunity
Abstract:
Inflammation underlies many important skin conditions. Recent work has highlighted the importance of inflammation in driving the extremely common scalp condition of dandruff. Although inflammation can act initially to help repair damaged skin, a persistent inflammatory response can perpetuate damage, leading to increased epithelial turnover and decreased epithelial permeability barrier function that characterises the abnormal skin function in dandruff. Triggers to this inflammatory response are not clear, but much evidence shows the importance of the fungal skin commensal of the genus Malassezia in initiating and perpetuating this condition. One mechanism by which Malassezia could produce an inflammatory response in skin is through activation of the inflammasome. The inflammasome is a multisubunit protein platform that leads to processing and activation of the cytokine interleukin-1beta (IL-1beta). IL-1beta is detected in increased amounts in dandruff sufferers and thus may play an important role in the development of this condition. We hypothesise that activation of the inflammasome by Malassezia spp. is an important factor in initiating and propagating inflammatory responses in dandruff. We have the following aims:
1. To define the ability of Malassezia globosa and restricta to activate the inflammasome in human keratinocytes.
2. To determine the composition of the inflammasome activated by these fungi.
3. To explore the interactions of sebum lipids and fungal metabolites on inflammasome activation.
The student will receive training in the following:
. Tissue culture of primary macrophages and other cells derived for wild type and select knockout mice
. Western blotting, and immunological methods
. CRISPR/Cas9 gene editing
. Single cell flow cytometry
. Cryoelectron microscopy for ultrastructural analysis of the inflammasome
. Systems biology approaches to understand the factors that tip the cell to activate the inflammasome.
Keywords: Inflammasome Dermatitis Innate Immunity
Abstract:
Inflammation underlies many important skin conditions. Recent work has highlighted the importance of inflammation in driving the extremely common scalp condition of dandruff. Although inflammation can act initially to help repair damaged skin, a persistent inflammatory response can perpetuate damage, leading to increased epithelial turnover and decreased epithelial permeability barrier function that characterises the abnormal skin function in dandruff. Triggers to this inflammatory response are not clear, but much evidence shows the importance of the fungal skin commensal of the genus Malassezia in initiating and perpetuating this condition. One mechanism by which Malassezia could produce an inflammatory response in skin is through activation of the inflammasome. The inflammasome is a multisubunit protein platform that leads to processing and activation of the cytokine interleukin-1beta (IL-1beta). IL-1beta is detected in increased amounts in dandruff sufferers and thus may play an important role in the development of this condition. We hypothesise that activation of the inflammasome by Malassezia spp. is an important factor in initiating and propagating inflammatory responses in dandruff. We have the following aims:
1. To define the ability of Malassezia globosa and restricta to activate the inflammasome in human keratinocytes.
2. To determine the composition of the inflammasome activated by these fungi.
3. To explore the interactions of sebum lipids and fungal metabolites on inflammasome activation.
The student will receive training in the following:
. Tissue culture of primary macrophages and other cells derived for wild type and select knockout mice
. Western blotting, and immunological methods
. CRISPR/Cas9 gene editing
. Single cell flow cytometry
. Cryoelectron microscopy for ultrastructural analysis of the inflammasome
. Systems biology approaches to understand the factors that tip the cell to activate the inflammasome.
People |
ORCID iD |
| Tom Evans (Primary Supervisor) | |
| Lizette Abraham (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/S50693X/1 | 01/10/2018 | 30/09/2022 | |||
| 2159522 | Studentship | BB/S50693X/1 | 01/10/2018 | 31/01/2023 | Lizette Abraham |