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Title Hibernation: the natural model of safeguarding organs from damage Winterslaap: het natuurlijke model om organen tegen schade te wapenen
Keywords transplantation Hibernation organ preservation
Researchers Prof. dr. R.H. Henning
Nature of the research Analysis of the mechanisms deployed by hibernators to protect from organ damage involves an array of molecular, functional and biochemical techniques, ranging from the basic ones (PCR, Western blot) to sophisticated cutting-edge technology (dual photon microscopy, intravital microscopy, Cre-lox knock-out models, single cell sequencing, metabolism studies).
Fields of study anesthesiology cell biology pharmacology
Background / introduction
Hibernation is characterized by a temporary lowering of metabolism and body temperature, which limits energy expenditure and provides an excellent strategy for survival. Small hibernators, such as hamster and mouse, alternate between periods of suppression of metabolism (from 75-99%) called torpor and shorter arousal periods with rapid and full restoration of metabolism and physiological functions. Remarkably, these repetitive swings between the extremes of physiology, with excess production of oxygen radicals, do not precipitate organ damage. Absence of organ damage is in sharp contrast to organs of humans that suffer considerably, e.g. during cooling and rewarming procedures as used in transplantation and major surgery.
In recent years, we have identified protective mechanisms, rooted in maintenance of endogenous H2S production and mitochondrial function. Based on these insights, we developed a whole new drug class, not only offering protection in cooling, but also in animals models of other diseases with excess oxidative stress, including type 2 diabetes and COPD.
Research question / problem definition
What is the role of endogenous H2S production in the induction of torpor and in precluding organ damage in hibernators and non-hibernators.
The project involves analysis of tissue from hibernators that lack H2S activity compared to normal animals. Depending on the interest and experience of the student, various tissues or cell models will be analysed starting with basic techniques.
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