Cell reprogramming, embryo development and genome integrity

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Cell differentiation and reprogramming are important research topics for the study of disease mechanisms and development of new cell-based therapies. Somatic cell nuclear transfer (SCNT) into enucleated oocytes was the original method used to confirm that differentiated somatic cells retain capacity for totipotency and can be completely reprogrammed through a second round of development. Genome damage and ER stress can be caused by a number of endogenous and exogenous factors, including reactive oxygen species, altered cell metabolism, xenobiotics and radiation. In response to DNA damage or ER stress cells activate reaction mechanisms that will lead to cell recovery, cell adaption or cell arrest/death. Although these mechanisms have been systematically investigated in somatic cells they are not well known in early developing embryos and during cell reprograming after nuclear transfer. There is evidence from studies in somatic cells indicating that genome damage and ER stress mechanisms are interdependent. However, their effects on development and cell reprogramming after nuclear transfer were not studied. Our research program will investigate the molecular pathways involved in the repair of DNA double-strand breaks during early embryo development and cell reprogramming after SCNT. We will also study how genome damage and ER stress mechanisms are interrelated in early developing embryos and explore their effects on cell reprogramming and differentiation. The proposed research will reveal the link between DNA damage and/or ER stress in early embryo development, cell reprogramming after SCNT, and embryo cell homeostasis, fate and differentiation. The proposed research program will also support student training and graduation of Highly Qualified Personnel (HQPs) in basic and applied sciences, and cutting edge technology.