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The NIH Catalyst from the Deputy Director for Intramural Research — Fostering Communication and Collaboration The nihCatalyst A Publication fob NIH Intramural Scientists National Institutes of Health i Office of the Director Volume 8, Issue 6 November-December 2000 NIH Research Festival Translational Research Running with the Genome: Jean Li d Cadet: NIH Gets To Work with the ‘Working Draft’ A Bridge at NIDA by Cynthia Delgado by Fran Pollner he “working draft” se- r ean Lud Cadet is equally at home quence of the human I upstairs and downstairs in the genome, delivered to building that houses the NIDA in- T | the desktops of the biomedi- Jamural research program at the cal community this summer, Johns Hopkins University Bayview may become the most “dog- campus in Baltimore. eared” work-in-progress the On the fourth floor, Cadet runs the world has ever known. four labs that make up the Molecu- Unlike the first draft of a lar Neuropsychiatry Unit, of which medical text that requires cor- he is chief; and on the first floor, he rections and updates before directs NIDA’s clinical research pro- it is finally printed, the gram, overseeing the inpatient re- genome’s first draft is out search unit, the outpatient research there, and some NIH investi- program, an adolescent clinic that fo- gators are using it to make cuses on smoking new discoveries while oth- cessation, and the — ers are arranging the data to 70 currently active make the material even more clinical protocols meaningful as a resource to all of which are the research community. strategic use of the HGP’s data aided conducted on-site. Simultaneously, the working draft is the discovery of a new family of recep- Upstairs, research- constantly growing, as sequencing data Taste,” ers are charting tors (see “An Acquired page 6). pours in, nonstop, from centers around and figuring out the world. The working draft—which The ABCs of Sequencing ways to prevent—the neurodegen- was 85-90 percent complete when it was Stage 1 of the HGP involved studying erative effects of illicit daigs in the announced in June should be entirely organizing the from each chro- brains of mice. Downstairs, they are — and DNA filled in by year’s end. The finished prod- in a process as map- documenting cognitive and hemody- mosome known uct (see description below) is anticipated ping. For physical mapping, each chro- namic deficits induced by these drugs in the year 2003, Eric Green said at the mosome is broken up into larger or in the brains of long-term human us- NIH Research Festival plenary session smaller pieces and isolated as DNA ers—and the persistence of these on “The Utility of Whole Genome Se- continued on page 6 effects, thus far, despite up to one quences: Early Glimpses of the Se- month’s abstinence. quence-Based Era.” CONTENTS The paths between the first and Calling the human genome a “24-vol- fourth floors are well traveled, and 1 6 ume encyclopedia set volumes 1-22, Running Sequencing when Cadet’s working in one loca- — X, and Y,” Green, chief of NHGRI’s Ge- With the Genome anid an AcqiAcquired Taste tion, he’s never far from the other, nome Technology Branch and director either physically or mentally. The Jean Lud Cadet: 8-9 of the NIH Intramural Sequencing Cen- A Bridge at NIDA Eureka: hope is that the cellular and molecu- ter, presented an overview of the fun- Hepatitis A Vaccine lar mechanisms of toxicity unraveled Thioether Bond damentals of the Human Genome Project in the lab will be brought to bear on From the DDIR: Cyclodextrins (HGP). the prevention and treatment pro- Planning for Change Rounding out the session, NCBI’s Greg White Knights grams in the clinic. Schuler described the computational pro- 3 When he arrived at NIDA, in 1992, Awards and Events 10-15 grams rapidly being developed to tackle Cadet had an agenda: to identify the Recently Tenured the task of assimilating and utilizing the long-term neurological effects of data—and Nick Ryba, chief of the NIDCR Prion Profiler 16 continued on page 4 Reed Wickner Catalytic Questions Taste and Smell Unit, reported on how The NIH Catalyst From the Deputy Director for Intramural Research Planning for Change in Biomedical Research unning the NIH has been described as equiva- tegrate into tissues and organs, and how these or- lent to steering an aircraft carrier—you can- gans produce organisms that interact with their en- Rnot turn on a dime and you have to think vironments. way ahead to keep from running aground. Bio- To satisfy these scientific imperatives, we need medical research is entering an era of enormous resources to allow creation of new animal mod- change, and we all need to start thinking about els—housing transgenic mice alone is a major re- how these changes will affect how we will do re- source commitment—and the requirements for search in—the future. Scientists are by nature con- zebrafish and large animal models will be substan- servative “If it ain’t broke, don’t fix it!” is a favor- tial. We are currently planning a new central vi- ite phrase of many bench scientists in describing varium on campus that will provide the space and their experimental approaches. But even the most flexibility to support these models and resources conservative of us realize that the future will not for histopathology, genetic manipulation, behav- look like the present. What should the intramural ioral analysis, and special surgery. program at NIH be doing to stay one step ahead of We will also need resources to support high-reso- new developments in biomedical research? lution structural studies. Currently, the NIH intra- We will undoubtedly need to deal with the enor- mural program supports a dedicated X-ray beam mous quantities of data currently being loaded into line at Brookhaven and one at Argonne for our central databases: genome sequences; microarray crystallographers. We have also upgraded our high- gene expression analyses as a function of develop- resolution electron microscope facilities, which will ment, disease, tissue type, etc.; complete medical be housed in Building 50, and we are planning for records, including radiological and pathological im- larger and larger magnets for high-resolution NMR ages; and the entire world’s literature at our finger- studies of molecular structure. For clinical imaging tips. We need networks that allow quick and easy research, we have a shared in vivo NMR center, access to this information, soft- and the new animal imaging fa- ware that predigests information cility will open in 2001. These or displays it in ways that are What should the facilities will put intramural NIH meaningful to us, and appropri- at the forefront of the technol- ate computer terminals for all INTRAMURAL PRO- ogy needed to support our re- scientists at NIH. The leadership search. of NIH has been working with GRAM AT NIH BE The design of our new labora- Al Graeff, the director of the tory buildings reflects the chang- Center for Information Technol- DOING TO STAY ONE ing nature of biomedical re- ogy, and with IT staff in the In- STEP AHEAD OF NEW search. Each of the new build- stitutes and Centers to be sure ings on campus has a basic in- that the most flexible infrastruc- DEVELOPMENTS IN terstitial design, which means ture exists to support these sci- that all of the support utilities for entific demands. The Clinical BIOMEDICAL RE- the labs are on floors layered be- tween the lab floors. This will Center has taken the lead in de- SEARCH? veloping a state-of-the-art Clini- make it easy in the future to cal Research Information System change and maintain plumbing, (CRIS) to replace our outmoded electrical, and air supplies to the Medical Information System (MIS). This develop- labs without disrupting the laboratories themselves. ment takes money and talented individuals, and Other elements of new lab design include com- we are making good progress on both fronts. puter networking, electrical supply that meets the The scale of many of our laboratory activities is high energy needs of current equipment, and more also undergoing great change. For example, in the efficient heating and cooling systems. And all of 1940s and 1950s, we were content to purify an the new buildings bring natural light and more space enzyme and demonstrate an activity; in the 1960s to our researchers. The NIH Master Planning pro- and 1970s, we wanted to clone and sequence the cess has provided a mechanism for rational growth enzyme; in the 1980s and 1990s, we expected to and renovation of our campus, and we are cur- do all of these and also crystallize it to determine rently considering other ways to meet our burgeon- structure, map the gene, and create a genetic model ing space needs. lacking or mutating the enzyme to determine its Finally, the vast power that these new research function. In the new millennium, no one is satis- tools give us also brings new responsibilities. Cur- fied with one enzyme—we want to characterize rent ethical concerns about clinical research are a the complete family of such enzymes, its whole direct result of our increasing ability to restructure evolutionary tree, and perhaps the entire pathway human genes and human bodies. Our planning for in which the enzyme resides. the future must include oversight systems to reas- In the not too distant future, we will be combin- sure both ourselves and the public that we are tak- ing physiological and molecular information to gain ing the right approaches and continuing to serve insight into how cells actually work, how they in- humanity.
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