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I have experience on the development of new strategies to generate transgenic bovine and porcine embryos for biotechnological applications by nuclear transfer NT , Intracytoplasmic sperm injection ICSI and in vitro fertilization IVF. The current project is oriented towards embryology in human, mouse and bovine models. I will have the opportunity to develop genomics skills single cell RNA sequencing as well as fluorescence microscopy.
I am also expected to take on training others in the methodologies to carry out at least the basic aspects of embryonic gene editing research. Lanner, his group and the facility scientists at the Chair will provide me the training in both the experimental procedures and the state of the art data analysis. This will enable me to successfully develop my project and generate improved bovine models with a series of genetic modifications to elucidate X-chromosome inactivation as well as how lineage specification and pluripotency is controlled in the early embryo.
Cells undergo an intermediate state of co-expression of lineage-specific genes, followed by a concurrent establishment of the trophectoderm, epiblast, and primitive endoderm lineages, which coincide with blastocyst formation.
Another elusive facet of early human development is X chromosome dosage compensation. In mouse, imprinted inactivation of the paternal X chromosome initiates around the 4-cell stage and is mediated by cis coating of the silenced X chromosome with the long non-coding RNA Xist. Female cells of all three lineages achieve dosage compensation of X chromosome RNA levels prior to implantation. However, in human, XIST is transcribed from both alleles throughout the progression of this expression dampening, and X chromosome genes maintain biallelic expression while dosage compensation proceeds.
Similar insights into the early bovine development are severely limited. The combination of recent discoveries in genetic engineering, particularly gene editing and the latest improvement in bovine reproduction technologies e. We will initiate genome editing in bovine embryos to elucidate how lineage specification and pluripotency is controlled in the early embryo, and how does X chromosome dosage compensation occurs.