INFECTIOUS DISEASES SEMINAR SERIES
Dr. Xiaolin Nan
Assistant Professor
Department of Biomedical Engineering
School of Medicine
Oregon Health and Science University
Topic: “Single Molecule Super-resolution Imaging Reveals a Dimeric Ras/Raf Signaling Module”
Abstract:
The Ras/Raf signaling module regulates cell proliferation and other essential cellular functions, and deregulated activation of this module is frequently linked to human cancers. Despite extensive research, efforts on targeting Ras and Raf for cancer therapeutics have only had limited success, urging a thorough re-examination of the molecular mechanisms by which these oncoproteins are regulated. We have employed photoactivated localization microscopy (PALM), a powerful single-molecule imaging technique that delivers nanometer spatial resolution and single-protein counting capability, to study Ras and Raf signaling in intact mammalian cells. We first demonstrate that when combined with quantitative image analysis, PALM is capable of directly resolving individual proteins and protein complexes such as dimers and oligmers in intact mammalian cells. With this quantitative imaging approach, we show that Raf forms dimers under various activation conditions including the presence of Ras-GTP and treatment with small molecule Raf inhibitors. These observations provide direct evidence for Raf dimerization and its involvement in cell signaling. More interestingly, quantitative single molecule imaging of cells expressing tunable levels of mutant Ras revealed that Ras-GTP also acts as dimers in activating Raf/MAPK. Biochemical assays further confirmed Ras-GTP dimer formation is both necessary and sufficient to activate MAPK signaling. Taken together, these findings suggest that the Ras/Raf acts as a dimeric signaling module of which the basic functional unit consists of two copies of Ras and Raf proteins. This important discovery calls for revisions to textbook models of Ras/Raf signaling, and provides the molecular basis for alternative and potentially more effective therapeutic strategy against Ras-driven tumors.
Time: 16:00, April 9 (Tuesday)
Place: Medical Science Building B301
Host: Dr. Ye Xiang
Light Refreshments will be served!!!
Background
The Centre for Infectious Diseases Research is holding a weekly seminar series. The seminars will be a great opportunity to hear speakers from both within and outside China speaking on a variety of subjects of interest to all those engaged in microbiology/immunology and allied disciplines. The coordinator of the seminar series is Babak Javid, and he would be delighted for fellow faculty to get in touch with regards to possible speakers to invite.
The seminars will also be of great interest to graduate students in life sciences, so we would appreciate PIs encouraging their students and post-docs to attend. By way of encouragement, we will be providing light refreshments to attendees.
If you are interested in meeting with the speaker, please email Babak Javid at bjavid@gmail.com.
We hope that this seminar series will prove to be a valuable addition for both training and scientific dialogue at Tsinghua, and look forward to seeing you there.
