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Gewählte Doctoral Thesis:

Sarah Kerschbaum (2021): Investigation of HSF1 inducers and the establishment of a burn wound model.
Doctoral Thesis - Institut für Pflanzenbiotechnologie und Zellbiologie (IPBT), BOKU-Universität für Bodenkultur, pp 90. UB BOKU obvsg

Data Source: ZID Abstracts
The heat shock response (HSR) is one of the major stress response pathways of the cell, that is tasked with restoring cellular protein homeostasis after stress injuries through upregulation of the heat shock proteins. However, after a severe but not lethal heat injury the activation of the HSR is delayed and the heat shock protein expression is not upregulated. Burn wound healing is further complicated by a process termed ‘burn wound progression’, during which so far viable tissue becomes necrotic, resulting in delayed wound healing, increased scarring, and mortality. I hypothesised that a controlled moderate activation of the HSR immediately after a heat injury could improve cell survival. Since the heat shock factor 1 (HSF1) is the key regulator of the HSR, I used a dual-luciferase reporter cell line to accurately measure HSF1 activity. Additionally, I measured the expression of the natural target genes of the HSR, the heat shock proteins and cell viability. Several inducer substances were found to upregulate HSR activity without influencing cell viability. Other inducer substances showed significant differences between previously reported and measured HSR activation, indicating tissue specific differences in the regulation of HSF1. Further, I studied the HSR kinetics, cell viability and general condition of the cells after short but powerful heat shocks in human fibroblasts. This led to the discovery of a non-proliferating cell population that showed a senescent phenotype. Senescent cells display several characteristics that could account for processes associated with burn wound progression. Among other things, senescent cells develop a specific senescence-associated secretory phenotype that includes many cytokines and immunomodulatory factors, possibly contributing to the persistent pro-inflammatory response associated with burn wound progression. Additionally, senescent cells can spread the senescent phenotype contributing to the loss of proliferating cells.

Betreuer: Mach Lukas
1. Berater:

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