Project details

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Mimicking hibernation to preclude organ dysfunction in sepsis

Keywords:
Hibernation kidney Sepsis

Researchers:
dr. H.R. Bouma

Nature of the research:
translational, laboratory, animal, cell culture, patient material, experimental

Fields of study:
pharmacology internal medicine intensive care

Background / introduction
Sepsis is a life-threatening response to infection, which may lead to multiple organ dysfunction syndrome and, potentially, death of the patient. Induction of a persistent hypermetabolic state by sepsis provokes mitochondrial dysfunction, which plays an important role in the pathogenesis of organ injury. Mitochondrial dysfunction plays a central role in the pathophysiology of organ dysfunction during sepsis. Yet, no therapy is available to preclude mitochondrial dysfunction in sepsis. Hibernators also face such hypermetabolic state in the repetitive, brief phases of normothermy intersecting hibernation, during which they however maintain mitochondrial homeostasis. As compared to non-hibernators, hibernating animals have a superior resistance to oxidative stress and are able to maintain mitochondrial homeostasis despite extreme physiological conditions associated with hibernation. H2S governs cytoprotective effects by preserving the production of ATP and upregulating anti-oxidant, anti-apoptotic and anti-inflammatory pathways. In this project, we will assess whether mimicking protective mechanisms of hibernators and precludes mitochondrial injury and preserves renal function during sepsis. Translating the mechanisms of hibernators into clinical applications, might have major relevance for patients with sepsis.
Research question / problem definition
Can protective mechanisms of hibernating animals be exploited for patient care?
Workplan
The project is run by MD/PhD-students, master students medicine and biomedical science, technical medicine and bachelor students medicine. We have opportunities for JSM pilot projects, scientific internships and MD/PhD projects. The workplan will be made together with the supervisor(s) in this project and may consist of animal and/or cell culture experiments, and molecular analysis of these samples and samples derived from patients with sepsis. As such, the student will learn to perform translational, experimental research with a focus on state-of-the-art molecular techniques in an experimental laboratory.
References
http://www.mitochondrialresearch.nl
http://hibernation.sepsis.science
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