CCAAT/enhancer binding protein (C/EBP) transcription factors regulate cell proliferation and differentiation in various cell types. Due to alternative initiation of translation, C/EBP alpha and beta are expressed as different protein isoforms, which may display antagonising biological functions. Disturbed isoform ratios are presumed to be involved in tumourigenesis. Recently, it was discovered that C/EBPs are expressed in bone tissue, and involved in bone-specific gene regulation. Preliminary data obtained with C/EBP beta deficient mice also imply a function in bone development and ectopic expression of the small C/EBP beta isoform suggests a role in bone tumourigenesis (osteosarcomas).
The aim of this project is to clarify the biological function of C/EBP beta in both normal bone development and in osteosarcomogenesis. Bone specific functions of C/EBP beta will be investigated by means of histological, cell biological and molecular biological comparisons of wild type and C/EBP beta deficient mice. Mesenchym al stem cells derived from C/EBP beta deficient mice will be used to delineate in which stage(s) of osteoblast differentiation C/EBP beta is involved. In order to resolve the functions of distinct C/EBP beta isoforms in osteoblast differentiation and in tu mourigenesis, they will be ectopically expressed in osteoblasts.
Knock-in mice that express only the small isoform of C/EBP beta were recently generated and will be analysed for alterations in bone biology. The advanced research training on molecular genetics in mouse models will take place at the MDC within a multidisciplinary setting where basic and clinical research meets biotechnology. The applicant, Jeske Smink, will acquire knowledge and skills in molecular genetics that are highly relevant in clinical studies. In addition, the host will benefit of Jeske Smink's expertise on bone biology. The fellowship will help to pursue her goal to become an independent and leading scientist in molecular bone biology.
Field of science
- /medical and health sciences/basic medicine/physiology/homeostasis
- /natural sciences/biological sciences/genetics and heredity
- /natural sciences/biological sciences/molecular biology/molecular genetics
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
- /medical and health sciences/medical biotechnology/cells technologies/stem cells
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