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香 港 大 學 - 巴 斯 德研究中心 H K U-Pasteur R es e a rc h Ce nt re Fighting infectious diseases through biological research and teaching The HKU-Pasteur Centre, Dexter HC Man building (HKU-PRC) is a non-profit organization cre- cell biologists, immunologists and chem- ated in 1999. Institut Pasteur, a world ists, the centre’s research is focused on leader in infectious disease viruses that represent a threat to public research, Hong s u r rc V a i e h Kong. The centre builds on syn- s Ne tw or k ergies between its founding partners with the goal of strengthening the Pa ste Kong, China and the greater Asian region. In its fight Courses collaborative project in Hong International create HKU-PRC as a long-term e University of Hong Kong (HKU) to health and economic stability in R teamed up with the prestigious against infectious diseases, HKU-PRC is a leading partner in ur international collaborations and networks, such as the Institut Pasteur existing pole of excellence in infectious International Network, and organizes the disease research and teaching. Equipped Pasteur-Asia Virology courses to teach and with a state-of-the-art research laboratory train a small number of outstanding Asian and an international team of virologists, students. Institut Pasteur, Paris Discovery of the Plague bacteria in Hong Kong HKU Faculty of Medicine Founded in 1887 after Louis Pasteur, the “father of modern microbiology”, had successfully developed the vaccine against rabies. Institut Pasteur is a non-profit private foundation dedicated to public health worldwide, with a long history of breakthrough discoveries, such as vaccines (diphtheria, yellow fever, poliomyelitis, hepatitis B) and identification of several etiologic agents of infectious diseases including HIV. Eight Pasteurians have been awarded Nobel prizes. In 1894, Pasteurian Alexandre Yersin, who had trained under Louis Pasteur, discovered in a groundbreaking seven days the bacteria responsible for the terrifying Black Death Plague (still known after his name as Yersinia pestis) in his mat-shed laboratory constructed in Hong Kong Island’s Kennedy Town district. Founded in 1910, the University of Hong Kong (HKU) is the oldest established tertiary education faculty in the Special Administrative Region. For over a century, HKU's Faculty of Medicine has been at the forefront of medical research. Its teams have tracked down and identified numerous pathogens responsible for locallyemerging infectious diseases, including Influenza viruses and the SARS coronavirus. Antiviral target & drug discovery research programme “ There is science and the applications of science, bound to each other like fruit to the tree that bears it.” Louis Pasteur Research: The need for new antivirals SARS-CoV: The search for a vaccine The emergence of new infectious diseases is a In 2003/2004, the centre’s activities were part of a research-driven response consequence of the increase in international of the international scientific community to the SARS outbreak. We travel, climate changes, more intensive agricul- developed a candidate vaccine against SARS which has been successfully tural practices and shifting demographics. As tested in experimental animals at the US National Institutes of Health. these factors are unlikely to change in the The centre’s research output on SARS-CoV will foster understanding of this foreseeable future, the international community must establish the new human pathogen and help the international scientific community capability to detect, contain and treat new diseases promptly in both devise strategies against SARS and related coronavirus infections. the developed and developing worlds. There is an overwhelming need for effective antiviral vaccines and therapeutics to better treat existing AIDS, Hepatitis C, Avian Influenza and Dengue Fever: and emerging viral infections. New therapeutics are needed Our fundamental and applied drug research programmes are closely Research: Our vision linked. HKU-PRC employs state-of-the-art genomic research tools, HKU-PRC’s research is designed to elucidate the fundamental biological imaging and high throughput technology to identify new small processes of the viruses which cause SARS, AIDS, Hepatitis C, Dengue molecule inhibitors of virus replication. New molecules are identified Fever and Avian Influenza. A better understanding of the biology of from synthetic compound libraries and Traditional Chinese Medicine- these viruses will reveal vulnerabilities which can be attacked through based libraries (established by our partners at SIMM in Shanghai) with a therapeutic invention. Our vision is to translate scientific discoveries single goal: to bring new antiviral compounds from the research phase into applications to benefit society. to the clinic. Intellectual property and business development of HKUPRC's discoveries are managed by Institut Pasteur in Paris, a world leader in technology transfer from academia to the private sector. Understanding the virus strategy Viruses are true parasites, needing the support of human cells to live. Despite their microscopic size, viruses hijack and manipulate complex International collaborations human cellular processes to achieve their own multiplication. Infection HKU-PRC is a leading partner in international networks and collaborations by viruses may provoke cell suffering and death, leading to the damage with France, Europe, China, Japan and the United States. of entire organs and the death of the infected patient. • Institut Pasteur, Paris, France • Institut Pasteur Asia network (China, Cambodia, Korea, New Caledonia, Vietnam) Our research provides answers to key questions: How does the virus • HKU Faculty of Medicine, Hong Kong interact with the cell, and which cell components help the virus enter? • Shanghai Institute for Materia Medica, China How does it assemble its individual building blocks to make a new • European Union networks on SARS and Dengue Fever infectious virus? Answering these questions is our scientific mission, • National Institutes of Health, Bethesda, USA which will lead to new strategies to combat viruses through vaccines • University of Tokushima, Japan and therapeutics. For more information on our research programme, please contact us at: [email protected] Meeting new infectious challenges Knowing our enemies to better combat them Genomics technology By the late 20th century, about 30 new infectious diseases had been identified, including HIV/AIDS, hepatitis C, variant Creutzfeldt-Jakob disease (vCJD), Nipah virus, several hemorrhagic fevers, avian flu and SARS. In addition to human morbidity and mortality, the economic costs of epidemics are tremendous; the 2002/2003 SARS outbreak cost an estimated US$ 30 billion. Viruses are true intracellular parasites. They need the cell’s machinery to accomplish replication. To enter host cells, viruses use surface protein projections which interact with cellular receptors — as a key fits a lock. Greater understanding of such interactions will lead to new, efficient techniques to block viral entry and therefore infection. Understanding the function of specific interactions between viral and cellular proteins is the key step to identifying new antiviral drugs. High throughput protein-interaction technologies are combined with advanced biochemistry, cell biology and virology methods to identify virus-cell interactions and characterise the specific complex mechanisms used by viruses to hijack cellular machinery. Interfering with these interactions with drugs can lead to new antiviral strategies. Institut Pasteur International Network: 10,000 staff in 29 institutes across 5 continents “The microbe is nothing, the terrain everything” Louis Pasteur St. Petersburg Bruxelles Lille Paris Sofia Rome Laval Alger Tunis Bucarest Athenes Seoul Teheran Shanghai Casablanca / Tanger Hong Kong Hanoi Dakar Niamey Pointe-à-Pitre Abidjan Cayenne Phnom Penh Bangui Yaounde Nha Trang Ho Chi Minh Ville Antananarivo Noum Institut Pasteur International Research Centres A unique organization, the Institut Pasteur International Network unites through biological research, education and public health activities. As a close to 10,000 staff from 29 institutions (including eight WHO Collab- member of the International Network, the HKU-PRC’s research is orative Centres) spread across five continents. The Network is dedicated enriched by the data and material collected by Pasteur Institutes to the surveillance, prevention and treatment of infectious disease throughout Asia. Hijacking the cells High throughput screening (HTS) Antiviral drugs Cells are the “building blocks of life”. The survival of cells in the human body is based on a delicate equilibrium of complex biological processes. During a viral infection this equilibrium is severely disturbed, eventually leading to virus-induced cell death. Through close collaboration with the Platform of Dynamic Imaging of the Institut Pasteur, HKU-PRC has access to the most advanced imaging technology to study high-speed virus protein movement through the cell. High throughput and high content screening (HTS-HCS) uses robotic technology to conduct hundreds of experiments simultaneously, which generates a large amount of experimental data in a very short time. HKU-PRC has successfully developed a target and drug discovery platform to identify the cellular genes required for viral infections and novel antiviral compounds. Discovery of new antiviral drugs will be the product of a greatly expanded understanding of viral biology combined with state-ofthe-art drug screening technology and original chemistry. At HKUPRC, an international and interdisciplinary team of highly qualified molecular and cellular biologists, virologists and chemists is working to identify new drugs from chemical libraries including Traditional Chinese Medicine. HTS image courtesy of Matrix Technologies. Our commitment to education: Pasteur-Asia Virology Courses “Chance favors only the prepared mind” Louis Pasteur The Pasteur-Asia Virology courses teach and train a small number of outstanding Asian students at the Master/MPhil and early PhD level. The courses are designed as a platform of excellence where young scientists meet, discuss and establish valuable contacts with the world’s best experts in Virology. Beyond teaching, we expect to stimulate and strengthen collaborations within the Asian Network of Institut Pasteur and other research institutes in the region, and give students orientation for their future careers. Pasteur-Asia Virology Course Meet the greatest Croucher-Pasteur exchange programme Co-organized by Institut Pasteur, HKU and HKU-PRC, the 2nd Pasteur-Asia Virology Course held in July 2005 was focused on respiratory viruses. Practical courses on state-of-the-art techniques in virus research are a key component of the teaching programme. During the course, selected students met the world’s best virologists in a master class environment, and had the rare opportunity to interact with Nobel Laureate in Physiology or Medicine Professor Rolf Zinkernagel. HKU-PRC actively promotes scientific reciprocity between Hong Kong and France through the “Croucher-Pasteur exchange programme”, to attract Hong Kong students to perform their PhD or postdoctoral research at the Institut Pasteur or the International Network. 1/F Dexter H.C. Man Building, 8 Sassoon Road, Pokfulam, Hong Kong Tel. : (852) 2816 8403 Fax : (852) 2872 5782 Email : [email protected] Website: www.hkupasteur.hku.hk Cover images: AIDS viruses : Coloured scanning electron micrograph of a T-lymphocyte blood cell (blue) infected with Human Immunodeficiency virus (HIV) (yellow), causative agent of AIDS. The surface of the T-cell has a lumpy appearance with large, irregular surface protrusions. Smaller spherical structures on the cell surface are HIV virus particles budding away from the cell membrane. The virus has infected the T-cell, and instructed the cell to reproduce many more viruses. By this viral budding the T-cell dies. Depletion of the number of T-cells in the blood is the main reason for the destruction of the immune system in AIDS. Magnification: x6,000 at 6x7cm size. x20,000 at 8x10". NIBSC / SCIENCE PHOTO LIBRARY. Antiviral molecule : Stavudine (d4T, Zerit®) is an oral medication used for the treatment of human immunodeficiency virus (HIV) infections. It is in a class of drugs called reverse transcriptase inhibitors. Stavudine is a success story of drug discovery in academia. Stavudine was first marketed in 1994, offering a new therapeutic solution for AIDS patients.