(ref. BAP-2019-765)Laatst aangepast : 8/01/2020
Embryonic cells in the earliest stages of development can generate the entire fetal body, a feature known as pluripotency. In mammals, this process involves dynamic changes in the removal and addition of methyl groups at specific positions in DNA. Changes in DNA methylation regulate gene expression and phenotype without altering the DNA sequence, constituting an important part of “epigenetics” research. The TET DNA dioxygenases erase DNA methylation by reiterative oxidation of 5-methylcytosine via 5-hydroxymethylcytosine and have major roles as epigenetic regulators in development and disease. As co-discoverer of the TET family, Prof. Kian Koh at KU Leuven studies the regulation of TET in pluripotency and early embryonic differentiation. Recent work by the group has opened new lines of investigation of TET1’s interesting roles in both embryonic and extra-embryonic lineages of the early post-implantation mouse embryo: www.news-medical.net/news/20170518/KU-Leuven-researchers-identify-vital-role-of-TET1-protein-in-earliest-stages-of-embryonic-development.aspx. PROJECT Using transgenic mouse strains generated in the laboratory, projects are available to investigate distinct epigenetic mechanisms regulating chromatin accessibility, gene expression and DNA methylation in lineage-specific embryonic versus extra-embryonic development, neurulation and cell fate reprogramming. The candidate will complement in vivo work conducted in mice with in vitro studies using stem cell cultures, to understand how gene expression are controlled by TET proteins in possibly different ways in different cell lineages. Ultimately, the studies will provide important information of how proper regulation of DNA methylation in early development can tip the balance between health and disease later in life, with a focus on aging-related neurological disorders, neurodegeneration and cancer. Selected Publications: * Khoueiry R, Sohni A, Thienpont B, Luo XL, Vande Velde J, Bartoccetti M, Boeck B, Zwijsen A, Rao A, Lambrechts D, Koh KP (2017). Lineage-specific functions of TET1 in the post-implantation mouse embryo. Nature Genetics 49, 1061-1072. * Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer CA, Mostoslavsky G, Lahesmaa R, Orkin SH, Rodig SJ, Daley GQ, Rao A (2011). Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8, 200-213.
• You will conduct independent research using techniques including mouse embryo dissection, cell culture and differentiation, genome editing, immunoprecipitation, ChIP-seq/RNA-seq and DNA methylation analysis.
• You will help to supervise PhD and Master students.
• You have good command of written and spoken English and are motivated to read and write manuscripts and research proposals.
• You have completed a PhD degree in molecular and cellular biology, biochemistry or a related biomedical field, within the past 3 years.
• You have a strong background in molecular/cell biology and in epigenetics and are motivated to learn and/or develop new techniques.
• Previous experience with bioinformatics data analysis will be an advantage.
• You desire international mobility and thrive in a multidisciplinary environment.
You will be paid salary and benefits based on KU Leuven employment guidelines. Postdoctoral fellows will receive contracts with yearly renewal; longer-term contracts are available upon successful competition for European or Belgian national fellowships.
For more information please contact Christina Vochten, (firstname.lastname@example.org).
The application file must include:
Cover letter containing statement of motivation
CV (summarizing education, positions, academic work and scientific publications)
Name and contact details of 3 referees.
KU 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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