Vol. 9 No.1 BIOTECH SCHOOL’S IN FOR SUMMER ho do you call when a new research course. It was a course in DNA manipulation, and technique debuts on the scientific stage we offered it because many people had gone W and you want to learn it fast? through school before these new tech- niques were taught. We had mostly faculty in the first classes—biochemists and physiologists who were trying to catch up on the new technology.” McGloughlin realized the initial DNA manipulation course targeted a finite audience since the techniques would now be part of a student’s education. There- UC Davis Biological Sciences fore, in 1990, the program offered a DNA is sent to division alumni, sequencing class. “When we offered the both graduate and class, people didn’t have automatic DNA undergraduate, and parents sequencers,” says McGloughlin. of current division students. Debbie Aldridge Once automatic sequencers supplanted We welcome news from During the summer, the UC Davis Biotechnology Program offers a series of intensive the do-it-yourself method the sequencing alumni for the “People” courses that focus on a particular biotechnology research technique. “We teach the class became obsolete. section; please protein analysis class (above) in conjunction with the UC Davis Molecular Structure Facility,” says Biotechnology Program Director Martina McGloughlin. “The students in the e-mail the editor at McGloughlin mentions another example class are exposed to techniques that make them aware we’re heading into an era during [email protected]. which we’ll be exploring areas beyond proteomics.” (continued on page 6) Or visit the alumni Web site at www.dbs.ucdavis.edu/ Hundreds of scientists, with backgrounds in THE BIG PICTURE academia and industry, have turned to the alumni/postcards/ hink big is the message Pete Smietana, UC Davis Biotechnology Program. and send us a postcard. Ph.D., Biophysics, 1979, hopes students Since 1988, the Biotechnology Program has offered Ttook away from the bioinformatics courses he two- to five-day intensive courses, open to the taught for UC Davis’ Biotechnology Program. public, that combine lectures with laboratories “The amount of information currently being designed to give participants hands-on experience generated in the life sciences is mind boggling,” with a particular research technique. says Smietana. “For example, in the company I’m Research News .............. 2 currently with, LumiCyte, Inc., we don’t run one Martina McGloughlin, director of the Biotechnol- microarray chip, think about the results for awhile, Solid as an Oak .............. 4 ogy Program, is aware of only a few other places in then run another. We run one microchip every Focus on Faculty ............. 7 the United States where people can take classes day—that’s about 10,000 data points a day, every similar to the ones her program offers. day. This quantity of information needs to be in People ........................... 8 The courses change to keep pace with and reflect electronic form. Most students coming out of In Memoriam ................. 9 developments in biotechnology. universities are not prepared for that.” While pursuing his doctoral studies in biophysics, ONTENTS Says McGloughlin, “In 1989 the Biotechnology Program offered its first intensive summer short (continued on back page) C WINTER 2001 1 precise control over the very fabric of various inheritable diseases, sensitivity to R ESEARCH NEWS matter. The techniques used in the sunlight and certain forms of cancer. UC Davis experiments might ultimately It has been difficult to figure out how the WATCH DNA UNZIP be developed to repair DNA in patients enzymes go about their routine business with genetic illnesses. IN MICROMOVIE in a molecular world too small to be glimpsed directly. Now, BY CARL T. H ALL Kowalczykowski and Reprinted with permission from the San his colleagues are Francisco Chronicle hoping to harness the process for medical sing some extraordinary camera purposes, including tricks, scientists at the University gene therapy and ultra- of California at Davis have pro- U precise delivery of duced Lilliputian action shots of molecu- DNA-repairing drug lar “motors” unwinding strands of DNA. payloads. Close to four years in the making, the “Our very simple goal grainy black-and-white movie stars an was to see in real time a enzyme called helicase, chugging along molecular motor running brightly lit tracks of fluorescent-dyed along a strand of DNA, microbial DNA. Jim von Rummelhoff something that has never The footage lasts only about a minute, Clip zips to No. 1. Professor of microbiology Stephen Kowalczykowski (above); Ronald been visualized before,” but it’s already attracting attention from Baskin, professor of molecular and cellular biology, and post-doctoral researcher Piero Kowalczykowski said. other researchers who are trying to peer Bianco produced a film that shows the enzyme helicase unwinding strands of DNA. In late It took a combination into the excruciatingly tiny realm of January, when the film was placed on the San Francisco Chronicle’s Web site, of sophisticated tools molecular motion. www.sfgate.com, it was clicked on more times than any other picture or video file. and custom engineer- “I have seen the movie,” said Ron Vale, ing to make the DNA a biochemist at UC San Francisco. “It’s stretch out sufficiently striking, and it’s completely clear.... It’s A report on the experiments appeared and hold still long enough to be photo- in the January 18 issue of the journal graphed while the enzyme molecules Nature. Authors include microbiologist were attached. Stephen Kowalczykowski; Ronald Baskin, Lighting was provided by special fluores- professor of molecular and cellular cent dyes that make DNA glow when it is biology, and post-doctoral researcher in its typical double-stranded form, but Piero Bianco, all of UC Davis, collaborat- not when the molecule has been un- ing with physicist Laurence Brewer and zipped into two single strands. colleagues at Lawrence Livermore National Laboratory. Glowing polystyrene beads were attached to one end of each piece of DNA to help The experiments described in Nature anchor them down. The researchers also build on earlier work—also led by UC Davis wielded laser beams as pairs of high- researchers—that showed how the precision “optical tweezers” to help keep helicase enzyme, called RecBCD—moves things under control. along in the fashion of an inchworm, jumping with each step 23 base pairs, the A single helicase molecule, attached to a chemical units that make up the message- DNA molecule, was then loaded into one (above) A series of "stills" taken from video tape of the encoding parts of the DNA double helix. channel of a Y-shaped micromachined enzyme helicase (large round spot) unwinding DNA. The film “flow cell.” The action began when the took nearly four years to complete. Powered by ATP, the same energy source ATP was added as fuel through the other that fuels our muscles, the enzyme roars arm of the “Y.” along at an astonishing speed—the At that point, the video camera began really amazing that you can now see equivalent of about 1,500 miles an hour, recording the scene through an optical single protein molecules in motion doing if DNA were scaled up to the width of a microscope, capturing the glowing DNA their work.” highway. as the enzyme molecules marched along The images underscore recent dramatic In its natural setting, this movement is a toward the polystyrene anchors. advances in the field of nanotechnology, a key part of natural DNA-repair processes. The enzyme molecules are too small to be discipline that scientists hope will allow Defects in this system are linked to seen one at a time, even under the 2 WINTER 2001 microscope. And technical problems made Teams of scientists examined the DNA leads the research. it impossible to use more advanced sequence for genes with particular The team uses a remote operated nanotech imaging methods that make functions. Britt, in collaboration with pictures by recording subtle atomic forces. Jonathan Eisen of The Institute for vehicle (ROV) owned and operated by Genome Research, looked for genes that the Monterey Bay Aquarium Research So the researchers had to settle for the repair damaged DNA. Institute (MBARI). The ROV Ventana indirect strategy of the special dye. As the is equipped with high-definition enzyme unzipped the DNA into its two “Twenty-seven genes were identified in cameras and laser measuring equip- separate strands, the light appears to Arabidopsis that were closely related to ment, and its arms can be fitted with blink out in the enzyme’s wake. The human disease genes,” said Britt. Of a variety of collecting and sampling pictures show the DNA strands seem- these, a third were DNA repair genes, equipment. ingly growing shorter and shorter. including genes linked to some types of Because of their strange and In the end, only the polystyrene bead is hostile habitat, deep-sea still visible, even though the unlit DNA bacteria have evolved still dangles in place. survival strategies found Kowalczykowski said additional experi- nowhere else on Earth. Far ments are planned to better understand from the sun, they live on how the enzymes work at the level of hydrogen sulfide seeping individual molecules—activity that from cracks in the seafloor biochemists traditionally have studied by and use nitrate in seawater mixing test tubes and beakers containing instead of oxygen. molecules by the millions. One example is Thiomargarita Looking at a single molecule as it namibiensis, giant bacteria that changes form is “a very powerful Jim von Rummelhoff grows to almost a millimeter approach,” Kowalczykowski said. “If you in size—100 times the size of want to know how a car works, you can The first complete genome sequence for a flowering plant, Arabidopsis thaliana, any other known bacterium.