学术报告1： Replication Stress Reduces the Fidelity of Nucleosome-mediated Epigenetic Inheritance
报告人：Xiangwei He, Ph.D.
Assistant Professor
Department of Molecular and Human Genetics, Baylor College of Medicine
主持人：朱永群 教授
讲座摘要：
Inheritance of epigenetic status is critical for maintaining gene expression profile and cell identity through cell generations. During cell cycle, the chromatin structure, a major carrier of epigenetic information, is duplicated in tight conjunction with DNA replication through the process called replication coupled nucleosome assembly. However, it is unclear how the fidelity of epigenetic inheritance is achieved. Here, we present evidence in fission yeast that replication stalling may directly cause reduction in the fidelity of nucleosomal inheritance. Using variegated gene expression (positional effect variegation, PEV) as the readout, we observed that replication stalling reduced the fidelity of chromatin structure inheritance at multiple loci in the genome. We are testing the mechanistic model that excessive amount of single-strand DNA (ssDNA) caused by replication stalling results in reduced fidelity of nucleosome inheritance coupled with replication. Our results suggest that replication stalling not only represents a threat to genome stability, but also increases epigenetic instability during cell divisions.
学术报告2：The Biology of Hiding the Corpse Clearance of Apoptotic Cells in C. elegans
Associate Professor
Verna & Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine
主持人：佟超 教授
讲座摘要：
Cells undergoing apoptosis during animal development or in adulthood are rapidly engulfed and degraded by phagocytes. The removal of apoptotic cells provides a safe means for eliminating unwanted and harmful cells from the body; furthermore, it prevents tissue injury, inflammatory responses, and auto-immune responses that could be induced by the content of dead cells. Despite the recent burst of the understanding of cell death, the mechanisms behind the removal of dying cells remain largely unknown. My laboratory is interested in understanding the recognition, engulfment, and degradation of apoptotic cells. We use the nematode Caenorhabditis elegans as a model organism to identify genes and delineate the pathways controlling these events, with the belief that what we learn from C. elegans will be translated to humans.
Previously, the maturation of phagosomes containing apoptotic cells, which results in their degradation, had not been systematically studied. We have established novel real-time imaging techniques in C. elegans, using which we quantitatively monitored the dynamic localization of multiple protein and lipid molecules during phagosome maturation in living embryos. Using these techniques, in combination with genetic approaches, we have identified the novel roles of a number of molecules in the maturation of phagosomes containing apoptotic cells and have delineated a signaling pathway led by the phagocytic receptor CED-1. Recently, we have focused on understanding the function and regulation of the lipid second messenger PtdIns(3)P for driving phagosome maturation. We have found that PtdIns(3)P triggers the initiation of phagosome maturation through recruiting sorting nexins SNX-9, SNX-1, and SNX-6 to phagosomal surfaces. These effectors promote the docking and fusion of intracellular vesicles to phagosomes using two distinct mechanisms. Furthermore, we have discovered that the level of PtdIns(3)P oscillates in two waves during phagosome maturation. This cyclic wave pattern, which is crucial for driving phagosome maturation, is programmed by a regulatory system composed of two PI 3-kinases (PIKI-1 and VPS- 34) and one PI 3-phosphatase (MTM-1). Our work sheds light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events.
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地点：医学院综合楼205报告厅
