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Pathogen Recognition and Signaling in Innate Immunity

CIT ID: 6222
Program date: Wednesday, May 07, 2008, 3:00:00 PM
Presented by: Shizuo Akira, Osaka University, Japan

Abstract:

Mammalian Toll-like receptors (TLRs) play a critical role in detection of invading pathogens as well as triggering of subsequent inflammatory and immune responses. Dr. Shizuo Akira's research has been instrumental in shaping our understanding of innate recognition by these receptors. Amongst the many major discoveries from his laboratory, his research has uncovered the role of TLR4 in the recognition of LPS; identified differential signaling by TLRs though selective use of adaptor proteins, such as MyD88 and TRIF; and described the ability of TLR9 to recognize bacterial DNA containing unmethylated CpG dinucleotides (pathogen-derived DNA) and TLR7 to recognize a derivative of imidazoquinoline, an antiviral chemical compound that is now used for treatment of genital warts caused by papilloma virus as well as single-stranded RNA of viruses, including influenza virus.

Furthermore, he recently demonstrated the role of two DExD/H box RNA helicases --- retinoic acid inducible protein-I (RIG-I) and melanoma differentiation-associated gene 5 (mda-5) --- in anti-viral responses by recognizing RNA in the cytoplasm in a TLR independent manner. Research from Dr. Akira's laboratory continues to be at the forefront of studies on recognition pathways for the induction of innate and adaptive immunity. Don't miss the opportunity to hear from this remarkable scientist.

Dr. Akira has been studying the role of Toll-like receptors (TLRs) and their signaling pathways mainly by gene targeting. He studied the molecular mechanisms of immunoglobulin gene rearrangement as a graduate student at Osaka University and for two years as a postdoctoral fellow at the University of California at Berkeley with Hitoshi Sakano. After returning to Japan, he studied IL-6 gene regulation and IL-6 signaling pathways in the laboratory of Tadamitsu Kishimoto, who discovered interleukin-6. Among his contributions, he cloned two important transcription factors involved in IL-6 signaling, NF-IL6 (also called C/EBP beta) and STAT3. In 1996, Dr. Akira left Dr. Kishimoto’s lab to become a professor of biochemistry at Hyogo College of Medicine. At that time he made the seminal observation that mice lacking the adaptor protein MyD88 were unresponsive to lipopolysaccharide (LPS), a major immunostimulatory component in the cell wall of Gram-negative bacteria, indicating that the LPS receptor uses MyD88 for signaling. MyD88 harbors a domain homologous to the cytoplasmic portion of IL-1 receptors and TLR family members. Therefore, he hypothesized that a member of the Toll-like receptor family was a candidate LPS receptor, and began making mice deficient in each of all members of the of TLR family. Together with Dr. Bruce Beutler’s findings with LPS unresponsive natural mutant mice, Dr. Akira demonstrated that TLR4 is essential for LPS responsiveness.

Dr. Akira went on to identify ligands of other TLR members using the TLR-deficient mice he had generated. In particular, he made the seminal discovery that bacterial DNA containing unmethylated CpG dinucleotides (pathogen-derived DNA) signaled via TLR9. Furthermore, he demonstrated that TLR7 recognizes a derivative of imidazoquinoline, an antiviral chemical compound that is now used for treatment of genital warts caused by papilloma virus as well as single-stranded RNA of viruses, including influenza virus.

Dr. Akira has subsequently been at the forefront of research that has resulted in major discoveries of TLR signaling and function. These include his demonstration for the first time that the signaling pathways by which individual TLRs signal differ from one another, thereby resulting in different gene expression and biological responses. Furthermore, he showed that the difference in signaling pathways among TLRs is due to selective usage of adaptor molecules, such as MyD88 and TRIF. Finally, he recently demonstrated that pathogen-derived DNA and RNA can be recognized in the cytoplasm in a TLR-independent manner, by signaling through RNA-helicases.

More information available at
http://www.jst.go.jp/erato/project/asm_P/asm_P.html

The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.

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Enhanced Audio Podcast 1:04:37   Enhanced Video Podcast 1:04:37



LaMontagne Lecture - Vaccines: The Health Insurance of the 21st Century

CIT ID: 6512
Program date: Tuesday, May 06, 2008, 2:00:00 PM
Presented by: Rino Rappuoli, Ph.D., Novartis, Siena, Italy

Abstract:

John R. LaMontagne Memorial Lecture

Poster

Rino Rappuoli, Ph.D., currently serves as Global Head Vaccines Research for Novartis Vaccines & Diagnostics (Siena, Italy), a position he has held since 2006.

Dr. Rappuoli’s research career has focused primarily on disease-causing bacteria, including the microbes that cause diphtheria, pertussis, cholera, and meningococcal meningitis. He has improved the scientific understanding of the molecular mechanisms by which these pathogens cause disease and applied this knowledge to the rational design of innovative tools to prevent infection and disease.

After receiving his Ph.D. from the University of Siena, Dr. Rappuoli conducted postgraduate research at Rockefeller University and at Harvard Medical School.

In the mid-1980s, while at the Sclavo Research Center in Siena, Dr. Rappuoli began heading a research project on Bordetella pertussis that led to the first recombinant bacterial vaccine against whooping cough. The mutant form of pertussis toxin used in the whooping cough vaccine was the first protein constructed by rational drug design to be approved for use in humans. His work at Sclavo also led to the development of a licensed conjugate vaccine against meningococcus C. Currently, Dr. Rappuoli is developing a vaccine against group B meningococcus using a genome-based approach termed reverse vaccinology. He also is leading research to develop new and improved influenza vaccines, including cell culture-based influenza vaccines and pandemic H5N1 influenza vaccines formulated with the novel MF59 adjuvant.

Dr. Rappuoli is co-founder of the field of cellular microbiology, a discipline that merges cell biology and microbiology. The scientific community adopted this new discipline after he and his colleagues published a review paper titled “Cellular Microbiology Emerging” in the journal Science in 1996.

Dr. Rappuoli has received numerous awards and honors throughout his career. He was elected to the U.S. National Academy of Sciences 2005, and also is an elected member of the European Molecular Biology Organization (EMBO). In 2005 he also was awarded the Gold Medal by the President of the Italian Republic for his contributions to public healthcare.

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Enhanced Video Podcast 1:09:55   Enhanced Audio Podcast 1:09:55



Challenges and Promise of Cell-Based Therapies

CIT ID: 6729
Program date: Tuesday, May 06, 2008, 8:00:00 AM
Presented by: NIH

Abstract:

The goal of the symposium is to understand the current state of basic and clinical pluripotent stem cell biology to help the National Institutes of Health (NIH) prioritize research with the greatest potential for clinical benefit. The symposium will enable NIH to determine which areas of high-priority research need to be emphasized and to develop additional Funding Opportunity Announcements to increase research in these areas.

For more information, visit
http://guest.cvent.com/EVENTS/Info/Summary.aspx?e=40331195-f7f7-44cb-80c9-4a4a87330300

Audio Podcasts   Video Podcasts
  Description Runtime     Description Runtime
Enhanced Audio Podcast - Part 1 1:58:56   Enhanced Video Podcast - Part 1 1:58:56
Enhanced Audio Podcast - Part 2 2:19:51   Enhanced Video Podcast - Part 2 2:19:51
Enhanced Audio Podcast - Part 3 2:25:49   Enhanced Video Podcast - Part 3 2:25:49



Ensemble Coding of Visual Information in Primate Retina

CIT ID: 6189
Program date: Monday, May 05, 2008, 12:00:00 PM
Presented by: E.J. Chichilnisky, Ph.D., The Salk Institute

Abstract:

Dr. Chichilnisky is an associate professor in the Systems Neurobiology Laboratories at the Salk Institute for Biological Studies. His laboratory focuses on how the retina processes visual information and transmits this information to the brain. This is accomplished by using a state-of-the-art 512-electrode recording system that allows the monitoring of hundreds of cells at once while stimulating the retina with spatial and temporal patterns of light. A key current area of interest is how retinal neurons collectively communicate visual motion information to areas of the brain responsible for motion perception and behavior guided by motion. A long-term goal of the research is to contribute to development of visual prosthetics, devices that could be implanted in the eye and substitute for retinal tissue damaged by disease or other trauma.

NIH Neuroscience Seminar Series

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  Description Runtime     Description Runtime
Enhanced Audio Podcast 1:06:10   Enhanced Video Podcast 1:06:10



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