Epigenetic Engineering Personal Statement

I have more than 15 years of experience working on embryonic development and assisted reproductive technologies. I consider myself an “embryology epigeneticist” who study epigenetics including DNA methylation, histone modifications, and histone variants on early embryos. My major interest is the cellular reprogramming processes.

I obtained my Bachelor (1996-2000) and Master degrees (2000-2002) in the Department of Animal Science, National Taiwan University, Taiwan. As a sophomore in 1997, I was amazed by the breaking news of Dolly, the sheep, the first cloned mammal created by somatic cell nuclear transfer (SCNT). I then joined my first mentor Prof Winston T-K Cheng’s lab (he is renowned as the world's first scientist to produce test-tube

It didn’t take me very long time to discover my hidden talents of micromanipulation once starting bench work and learning embryology. I generated my first batch of transgenic mice within few weeks during summer internship. During the last three undergrad semesters, I received a GPA of 3.6. Bearing this sheer passion about reproductive biotechnology, I motivated myself to apply for the Master of Science program. Continually focusing my research on transgenic animals and recombinant pharmaceutical medicine production, I accomplished my thesis “Generation and Analysis of Transgenic Mice and Dairy Goat Harboring the LA-hFVIII Gene.” Simultaneously, I created the first germline transmitted transgenic dairy goats in Taiwan. In addition, I received the scholarship of the Alumni of the Department of Animal Husbandry, NTU (overall GPA during the master program was 3.8) and won the Young Scientist Poster Award of the Chinese Society of Animal Science,

I investigated the roles of the histone variant H3.3 during oocyte-to-egg transition. I reveal that H3.3 mediates a balance between open and condensed chromatin that is crucial for the fidelity of chromosome segregation during early mouse development. Knocking down of H3.3 in fertilised mouse zygotes leads to developmental arrest at the morula stage. Loss of H3.3 leads to over-condensation and mis-segregation of chromosomes with corresponding high levels of aneuploidy. H3.3-deficient embryos have significantly reduced levels of markers of open chromatin, such as H3K36me2 and H4K16Ac. In addition, H3.3 KD embryos have increased incorporation of linker H1(Lin et al Development 2013). In addition, I have recently shown that Hira (an H3.3 chaperone) mediated H3.3 incorporation is involving the nucleosome assembly in the male genome to form a male pronucleus. Additionally, I overturned a long-lasting dogma that transcription of the mouse zygotic genome is minor and not required for development by demonstrating that instead of RNA Polymerase II (mRNAs), RNA Polymerase I (rRNAs) function is required for zygotic cleavage to 2-cells (Lin et al Developmental Cell 2014). On the basis of this work, I was selected for an oral presentation at the Cell Transcriptional Regulation in Development, Cell Symposium in July