报告题目一
时间：2017年12月30日13:40～14:10
Dicer functions at sites of replication-transcription collisions to protect genome integrity
报告人：任捷
Fellow，Cold Spring Harbor Laboratory，USA
报告摘要
Maintaining genome stability and faithfully inheriting the epigenetic information are major challenges in all eukaryotes. Nuclear RNA interference (RNAi) is an important regulator of transcription and epigenetic modifications, however, its function in response to these challenges and the underlying mechanisms remain elusive.
I have found a novel role for the RNAi protein Dicer in resolving replication-transcription collisions via the release of RNA polymerase II (Pol II). This allows Dicer to couple the spreading of heterochromatin with replication fork progression, providing a mechanistic link between heterochromatin inheritance by RNAi and DNA replication. Using genome-wide approaches, I have also revealed that the role of Dicer in managing collisions is not limited to heterochromatin, but is also important at highly transcribed genes, rDNA and tDNA. These novel Dicer-regulated sites strongly correlates with replication stress, DNA damage and genome instability. A striking example of this is at the subtelomeric rDNA repeats, where Dicer is required to release Pol II to facilitate DNA replication and to prevent homologous recombination, which would otherwise lead to loss of rDNA repeats during mitosis and meiosis. These results now provide a paradigm for Dicer action at transcription-replication collisions in various genomic contexts. Such collisions have a profound impact in genome and epigenome stability, and contribute to the molecular basis of cancer and ageing.
报告题目二
时间：2017年12月30日14:25～14:55
Structure Study: from Notch regulation to macromolecular machines
报告人：于洪军
Research Scientist，Van Andel研究所，USA
报告摘要
Notch pathway plays essential roles in metazoan development and tissue homeostasis, and its dysfunction is involved in tumorigenesis and other human diseases. Finer characterization of the complicated signaling and regulating network of Notch signaling is of growing clinical interest. Notch signaling can be regulated by differential O-linked glycosylation of Notch extracellular domain (NECD). We systematically characterized two key components-Rumi and XXYLT1-in Notch O-glucosylation pathway and revealed the molecular basis of these three Notch-modifying enzymes, including substrate recognition and chemical-biology mechanism. This gives a detailed view of how Notch NECD is O-glucosylated and also provides novel basis to modulate Notch signaling. Moreover, we identified multiple NOTCH pathway gene alterations that may compromise Notch function in cancers and genetic disorders, emphasizing the dysfunction of Notch signaling in these diseases, especially in squamous cell carcinomas. These functional and mechanistic insights will help to probe the role of Notch in human diseases and facilitate the development of novel Notch modulators.
We also used the cryoEM single particle analysis to characterize several macromolecular machines by solving their near-atomic structures. These efforts target the bacterial protein quality control system: AAA ATPase ClpB and an Archaea membrane-bound complex for energy-converting.
报告题目三
时间：2017年12月30日15:10～15:40
Fighting Superbugs
报告人：苏致嘉
Research Scientist，Case Western Reserve University，USA
报告摘要
Superbugs are strains of bacteria that are resistant to several types of antibiotics. Each year these drug-resistant bacteria infect more than 2 million people nationwide and kill at least 23,000 in the United State, according to the U.S. Centers for Disease Control and Prevention (CDC). Multidrug efflux transporters—a common and powerful resistance mechanism—are capable of extruding a number of structurally unrelated antimicrobials from the bacterial cell facilitating their survival in noxious environments. My current research is focused on elucidating the structure, assembly and fundamental mechanisms that give rise to multiple drug recognition and extrusion in these multi-drug transporters. Based on the structural information, therapies that inhibit multidrug efflux transporter activity have been rationally designed and developed. My major research approaches include X-ray crystallography, electron microscopy, microbiology, single-molecule FRET and library screening.
报告题目四
时间：2017年12月30日15:55～16:25
Innovative drug discovery
报告人：常炳圣
Principal Scientist，Pfizer（辉瑞制药公司）， USA
具体日程安排见链接：http://today.hit.edu.cn/news/2017/12-26/6441315121RL0.htm
