Rising Stars 2024 #2


Using single-cell transcriptomics to understand ovulation and drive contraceptive discovery

Dr. Britt Goods, Dartmouth College, USA

Description: Single-cell methods have revolutionized our ability to understand complex processes. My research leverages these methods, including single-cell RNA-sequencing, to better understand ovulation and inform drug discovery. Here, I will discuss some recent work we have performed to understand factors that drive ovulation over time with spatial transcriptomics datasets and how we have used this, plus data integration methods, to nominate novel drug targets.

Bio: Dr. Goods is currently an Assistant Professor of Engineering at The Thayer School of Engineering. She received her PhD in Biological Engineering from MIT and completed her postdoctoral training at the Broad Institute, the Ragon Institute, and the Institute for Medical Engineering and Sciences at the Massachusetts Institute of Technology. Her work is broadly focused in creating tools, approaches, and the requisite biological knowledge to address clinical problems in reproductive health. Current focus areas in the lab include investigating the role of immune cells in reproductive tissues, facilitating the discovery of non-hormonal contraceptives with bioinformatic and transcriptomic approaches, and the modeling of reproductive tissues ex vivo with culture and organoid systems. The long-term goal of Dr. Goods’ research is to improve the lives of people by building a better understanding of immunology and reproductive tissues, and translating those insights into therapeutics, diagnostics, and novel ways of both studying and monitoring reproductive and overall health.

Genomic imprinting mediated by maternal histone modifications

Dr. Azusa Inoue, RIKEN, Yokohama, Japan

Bio: I am studying how maternal proteins stored in mammalian oocytes regulate embryonic development. During my PhD training at the University of Tokyo, I found that NPM2, a maternal protein stored in nucleolus-like bodies of oocytes, contributes to sperm chromatin decondensation upon fertilization in mice (FASEB J 2010, Biol Reprod 2011). During postdoc training at the Zhang lab, I found that DNA methylation of the sperm genome is erased by Tet3-mediated oxidation followed by DNA replication-coupled dilution of oxidative forms of 5-methylcytosines during preimplantation development (Science 2011, Cell Res 2011, Cell Res 2012, Cell Rep 2015). Furthermore, I found that a histone chaperone HIRA is responsible for maternal histone incorporation into the paternal chromatin after fertilization, and that its inhibition results in the formation of nucleosome-free paternal pronucleus that curiously have a nuclear envelope without nuclear pore complexes (Nat Struct Mol Biol 2014). Moreover, I revealed that a repressive histone modification, H3K27me3, is transmitted from oocytes to embryos and regulate genomic imprinting in a germline DNA methylation-independent manner (Nature 2017, Genes Dev 2017, Genes Dev 2018). This new form of genomic imprinting is now termed “non-canonical imprinting”. Since I started own lab in 2018, we are studying how histone modifications are established in oocytes (Nat Genet 2021), how they are inherited by embryos, what functions they have (Genes Dev 2022), and how they are influenced by maternal environment.

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