Muscle epigenetics and long-term physical outcome after critical illness (ref. BAP-2023-268)
The Intensive Care Medicine Research Group is part of the department of Cellular and Molecular Medicine at the University of Leuven (Belgium). We are a highly successful, multidisciplinary, translational basic/clinical research team that combines a research laboratory with a large intensive care unit (ICU). This unique combination allows effective cross-talk between knowledge generated from patient studies and from animal and molecular studies in the laboratory. Our research focuses on critical illness, which is any disease state in which the function of one or more organ systems is impaired to the extent that the patient would die shortly when not receiving intensive medical care in the ICU to support the failing organs. Our overall objective is to unravel key pathways involved in critical illness-induced organ failure and long-term debilitating consequences after critical illness that may persist up to years after hospital discharge.
One of the severe complications that many patients are confronted with is the development of muscle weakness in the ICU. This ICU-acquired weakness has not only been associated with increased risk of acute morbidity and mortality, but also with worse long-term outcome. These patients may indeed continue to suffer from physical impairments up to years after the critical illness, compromising independency to perform activities of daily living and quality of life. The molecular mechanisms underlying these long-term functional impairments currently remain to be unravelled.Website unit
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).
- We are looking for a highly motivated, enthusiastic, critical, and creative person with a master degree or equivalent in a relevant field, such as Medicine, Biomedical Sciences, Bioscience Engineering, Biomedical Engineering, Bioinformatics, Biostatistics, Biochemistry, Biology, (Epi)genetics, … (or will obtain this degree in 2023)
- You are interested in "big data analysis" in the biomedical field and have (basic) experience in relevant statistical programming (preferably language R, or Python)
- You have good social and communicative skills and can work both independently and as a team player
- You have solid knowledge of English
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: email@example.com or Prof. dr. Greet Van den Berghe, tel.: +32 16 34 40 21, mail: firstname.lastname@example.org.You can apply for this job no later than June 28, 2023 via the online application toolKU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be.
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