Distributions and biogeochemical cycles of platinum in estuaries, the western North Pacific and its marginal seas.

学位の種別: 課程博士審査委員会委員 : (主査)東京大学准教授 小畑 元, 東京大学教授 須貝 俊彦, 東京大学准教授 芦 寿一郎, 東京大学准教授 小川 浩史, 東京大学教授 植松 光夫University of Tokyo(東京大学

Asymmetric parental genome engineering by Cas9 during mouse meiotic exit

Mammalian genomes can be edited by injecting pronuclear embryos with Cas9 cRNA and guide RNA (gRNA) but it is unknown whether editing can also occur during the onset of embryonic development, prior to pronuclear embryogenesis. We here report Cas9-mediated editing during sperm-induced meiotic exit and the initiation of development. Injection of unfertilized, mouse metaphase II (mII) oocytes with Cas9 cRNA, gRNA and sperm enabled efficient editing of transgenic and native alleles. Pre-loading oocytes with Cas9 increased sensitivity to gRNA ~100-fold. Paternal allelic editing occurred as an early event: single embryo genome analysis revealed editing within 3 h of sperm injection, coinciding with sperm chromatin decondensation during the gamete-to-embryo transition but prior to pronucleus formation. Maternal alleles underwent editing after the first round of DNA replication, resulting in mosaicism. Asymmetric editing of maternal and paternal alleles suggests a novel strategy for discriminatory targeting of parental genomes

Switchable genome editing via genetic code expansion

Multiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation and Cas9 variants have accordingly been generated whose activity responds to small ligands, temperature or light. However, these approaches are often impracticable, for example in clinical therapeutic genome editing in situ or gene drives in which environmentally-compatible control is paramount. With this in mind, we have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by the cheap lysine derivative, Lys(Boc) (BOC). Genetic code expansion permitted non-physiological BOC incorporation such that Cas9 (Cas9BOC) was expressed in a full-length, active form in cultured somatic cells only after BOC exposure. Stringently BOC-dependent, heritable editing of transgenic and native genomic loci occurred when Cas9BOC was expressed at the onset of mouse embryonic development from cRNA or Cas9BOC transgenic females. The tightly controlled Cas9 editing system reported here promises to have broad applications and is a first step towards purposed, spatiotemporal gene drive regulation over large geographical ranges

Evidence-based Tool for Triggering School Closures during Influenza Outbreaks, Japan

Guidelines available to school administrators to support school closure decisions during influenza outbreaks are usually not evidence-based. Using empirical data on absentee rates of elementary school students in Japan, we developed a simple and practical algorithm for determining the optimal timing of school closures for control of influenza outbreaks