Index: Karolinska Institutet: KI North: Department of Medicine, Solna
Endoplasmic Reticulum Stress: friend or enemy of skin wound healing process?
Background Skin wound healing is the interaction of a complex cascade of cellular events that is activated as a response to tissue injury. Wounds that do not heal within three months are considered chronic and cause significant morbidity. Wound-related costs are estimated to be 2-4% of healthcare budgets in the industrialized world. Thus, there is major need of improving chronic wound treatments. During tissue regeneration, such as wound healing, cells show a high demand of protein synthesis. The endoplasmic reticulum (ER) is the largest organelle in eukaryotic cells and performs multiple essential cellular tasks including lipid synthesis, protein folding and calcium storage. Several cellular stress conditions that are common in the wound milieu lead to the accumulation of unfolded or misfolded proteins in the ER, causing “ER stress”. Eukaryotic cells have a signaling system to manage ER stress, which is termed the unfolded protein response (UPR). We previously studied the role of ER stress in human skin wound healing process using a transcriptomics analysis. This analysis, revealed alterations of several UPR genes, suggesting that ER stress is involved in human wound healing process. Aims Aim 1: Determine the level of ER stress in human acute and chronic wounds Aim2: Investigate the role of UPR in wound healing in vitro. Methods Methods 1: Human skin biopsies from intact skin, acute wounds and chronic wounds will be examined with different techniques. Expression of gene associated with ER-stress will be measured by qPCR. Levels of ER-stress markers will be quantified by western blotting and observed by immunohistochemistry. Methods 2: Primary dermal fibroblasts will be genetically manipulated or treated with drugs modifying the UPR. Then we will perform in vitro scratch assay to evaluate the role of UPR in fibroblast migration. We are looking for a highly motivated master student that is willing to dedicate a significant effort to this project. In return we will provide both hands-on and theoretical mentorship. The lab is well funded. |