This project will address the hypothesis that the development of epigenetic changes in muscle may contribute to the long-term persistence of weakness in ICU survivors, which in turn may provide a new target for therapeutic intervention.
Epigenetic mechanisms lead to functionally relevant changes in gene expression without altering the genetic code and have been implicated in permanent effects of transient environmental hazardous exposures/stressors on health. The most stable epigenetic change is DNA (de)methylation, which can persist for years and has been associated with long-lasting alterations in gene expression. Others include histone modification and expression of non-coding RNAs. We recently identified that critically ill patients in the ICU present with a different DNA methylation signature in skeletal muscle as compared with healthy controls, with many of the associated genes being highly relevant for muscle structure and function/weakness.
In precious muscle biopsies collected from ICU survivors years after the critical illness and from matched controls, we will now investigate in a genome-wide approach whether critical illness may lead to abnormal DNA methylation, accelerated biological ageing and/or altered expression of non-coding RNAs in the long term after ICU discharge, and how this relates to long-term gene expression, muscle damage and weakness. When relevant long-term epigenetic changes are identified, we will document the time course of these changes in muscle during ICU stay in relation to morphological, molecular and functional changes during critical illness, aiming to identify a window of opportunity for potential future intervention.
The project will be conducted under supervision of Prof. Dr. Ilse Vanhorebeek (Bio-Engineer), Prof. Dr. Greet Van den Berghe (Medical Doctor) and Dr Fabian Güiza (Engineer and Master in Artificial Intelligence).
The PhD candidate will become part of a multidisciplinary research team that is internationally recognized as the expert in research integrating Intensive Care Medicine and Endocrinology/Metabolism/Nutrition. The group’s landmark clinical/translational studies worldwide initiated major changes in the care for critically ill patients. We unraveled several mechanisms involved in persistent organ failure and in effects observed in randomized clinical studies, which identified new targets for intervention. The symbiosis between people of different educational background offers a unique stimulating environment to learn from each other.
We offer a full-time scholarship for 4 years. The position is initially offered for 1 year, renewable after a positive evaluation up to a total of 4 years, and is expected to result in the completion of a PhD.
For more information please contact Prof. dr. Ilse Vanhorebeek, tel.: +32 16 33 05 32, mail: ilse.vanhorebeek@kuleuven.be or Prof. dr. Greet Van den Berghe, tel.: +32 16 34 40 21, mail: greet.vandenberghe@kuleuven.be.