vol. 9 nomicrobiology.ucdavis.edu/kowalczykowski/pdf_files/dbs...the first complete genome sequence...

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WINTER 2001 1 Research News .............. 2 Solid as an Oak .............. 4 Focus on Faculty ............. 7 People ........................... 8 In Memoriam ................. 9 C ONTENTS BIOTECH SCHOOL’S IN FOR SUMMER Vol. 9 No.1 (continued on page 6) (continued on back page) UC Davis Biological Sciences is sent to division alumni, both graduate and undergraduate, and parents of current division students. We welcome news from alumni for the “People” section; please e-mail the editor at [email protected]. Or visit the alumni Web site at www.dbs.ucdavis.edu/ alumni/postcards/ and send us a postcard. W ho do you call when a new research technique debuts on the scientific stage and you want to learn it fast? Hundreds of scientists, with backgrounds in academia and industry, have turned to the UC Davis Biotechnology Program. Since 1988, the Biotechnology Program has offered two- to five-day intensive courses, open to the public, that combine lectures with laboratories designed to give participants hands-on experience with a particular research technique. Martina McGloughlin, director of the Biotechnol- ogy Program, is aware of only a few other places in the United States where people can take classes similar to the ones her program offers. The courses change to keep pace with and reflect developments in biotechnology. Says McGloughlin, “In 1989 the Biotechnology Program offered its first intensive summer short course. It was a course in DNA manipulation, and we offered it because many people had gone 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- fore, in 1990, the program offered a DNA sequencing class. “When we offered the class, people didn’t have automatic DNA sequencers,” says McGloughlin. Once automatic sequencers supplanted the do-it-yourself method the sequencing class became obsolete. McGloughlin mentions another example THE BIG PICTURE T hink big is the message Pete Smietana, Ph.D., Biophysics, 1979, hopes students took away from the bioinformatics courses he taught for UC Davis’ Biotechnology Program. “The amount of information currently being generated in the life sciences is mind boggling,” says Smietana. “For example, in the company I’m currently with, LumiCyte, Inc., we don’t run one microarray chip, think about the results for awhile, then run another. We run one microchip every day—that’s about 10,000 data points a day, every day. This quantity of information needs to be in electronic form. Most students coming out of universities are not prepared for that.” While pursuing his doctoral studies in biophysics, During the summer, the UC Davis Biotechnology Program offers a series of intensive courses that focus on a particular biotechnology research technique. “We teach the protein analysis class (above) in conjunction with the UC Davis Molecular Structure Facility,” says Biotechnology Program Director Martina McGloughlin. “The students in the class are exposed to techniques that make them aware we’re heading into an era during which we’ll be exploring areas beyond proteomics.” Debbie Aldridge

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Page 1: Vol. 9 Nomicrobiology.ucdavis.edu/kowalczykowski/PDF_files/DBS...The first complete genome sequence for a flowering plant, Arabidopsis thaliana, was published on Dec. 14 in the journal

WINTER 2001 1

Research News .............. 2

Solid as an Oak .............. 4

Focus on Faculty ............. 7

People ........................... 8

In Memoriam ................. 9

CO

NT

EN

TS

BIOTECH SCHOOL’S IN FOR SUMMER

Vol. 9 No.1

(continued on page 6)

(continued on back page)

UC Davis Biological Sciencesis sent to division alumni,both graduate andundergraduate, and parentsof current division students.We welcome news fromalumni for the “People”section; pleasee-mail the editor [email protected] visit the alumni Web siteat www.dbs.ucdavis.edu/alumni/postcards/and send us a postcard.

Who do you call when a new researchtechnique debuts on the scientific stageand you want to learn it fast?

Hundreds of scientists, with backgrounds inacademia and industry, have turned to theUC Davis Biotechnology Program.

Since 1988, the Biotechnology Program has offeredtwo- to five-day intensive courses, open to thepublic, that combine lectures with laboratoriesdesigned to give participants hands-on experiencewith a particular research technique.

Martina McGloughlin, director of the Biotechnol-ogy Program, is aware of only a few other places inthe United States where people can take classessimilar to the ones her program offers.

The courses change to keep pace with and reflectdevelopments in biotechnology.

Says McGloughlin, “In 1989 the BiotechnologyProgram offered its first intensive summer short

course. It was a course in DNA manipulation, andwe offered it because many people had gone

through school before these new tech-niques were taught. We had mostly facultyin the first classes—biochemists andphysiologists who were trying to catch upon the new technology.”

McGloughlin realized the initial DNAmanipulation course targeted a finiteaudience since the techniques would nowbe part of a student’s education. There-fore, in 1990, the program offered a DNAsequencing class. “When we offered theclass, people didn’t have automatic DNAsequencers,” says McGloughlin.

Once automatic sequencers supplantedthe do-it-yourself method the sequencingclass became obsolete.

McGloughlin mentions another example

THE BIG PICTURE

Think big is the message Pete Smietana,Ph.D., Biophysics, 1979, hopes studentstook away from the bioinformatics courses he

taught for UC Davis’ Biotechnology Program.

“The amount of information currently beinggenerated in the life sciences is mind boggling,”says Smietana. “For example, in the company I’mcurrently with, LumiCyte, Inc., we don’t run onemicroarray chip, think about the results for awhile,then run another. We run one microchip everyday—that’s about 10,000 data points a day, everyday. This quantity of information needs to be inelectronic form. Most students coming out ofuniversities are not prepared for that.”

While pursuing his doctoral studies in biophysics,

During the summer, the UC Davis Biotechnology Program offers a series of intensivecourses that focus on a particular biotechnology research technique. “We teach theprotein analysis class (above) in conjunction with the UC Davis Molecular StructureFacility,” says Biotechnology Program Director Martina McGloughlin. “The students in theclass are exposed to techniques that make them aware we’re heading into an era duringwhich we’ll be exploring areas beyond proteomics.”

Debb

ie Ald

ridge

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2 WINTER 2001

R E S E A R C H N E W S

WATCH DNA UNZIPIN MICROMOVIE

BY CARL T. HALL

Reprinted with permission from the SanFrancisco Chronicle

U sing some extraordinary cameratricks, scientists at the Universityof California at Davis have pro-

duced Lilliputian action shots of molecu-lar “motors” unwinding strands of DNA.

Close to four years in the making, thegrainy black-and-white movie stars anenzyme called helicase, chugging alongbrightly lit tracks of fluorescent-dyedmicrobial DNA.

The footage lasts only about a minute,but it’s already attracting attention fromother researchers who are trying to peerinto the excruciatingly tiny realm ofmolecular motion.

“I have seen the movie,” said Ron Vale,a biochemist at UC San Francisco. “It’sstriking, and it’s completely clear.... It’s

really amazing that you can now seesingle protein molecules in motion doingtheir work.”

The images underscore recent dramaticadvances in the field of nanotechnology, adiscipline that scientists hope will allow

precise control over the very fabric ofmatter. The techniques used in theUC Davis experiments might ultimatelybe developed to repair DNA in patientswith genetic illnesses.

A report on the experiments appearedin the January 18 issue of the journalNature. Authors include microbiologistStephen Kowalczykowski; Ronald Baskin,professor of molecular and cellularbiology, and post-doctoral researcherPiero Bianco, all of UC Davis, collaborat-ing with physicist Laurence Brewer andcolleagues at Lawrence LivermoreNational Laboratory.

The experiments described in Naturebuild on earlier work—also led by UC Davisresearchers—that showed how thehelicase enzyme, called RecBCD—movesalong in the fashion of an inchworm,jumping with each step 23 base pairs, thechemical units that make up the message-encoding parts of the DNA double helix.

Powered by ATP, the same energy sourcethat fuels our muscles, the enzyme roarsalong at an astonishing speed—theequivalent of about 1,500 miles an hour,if DNA were scaled up to the width of ahighway.

In its natural setting, this movement is akey part of natural DNA-repair processes.Defects in this system are linked to

various inheritable diseases, sensitivity tosunlight and certain forms of cancer.

It has been difficult to figure out how theenzymes go about their routine businessin a molecular world too small to be

glimpsed directly. Now,Kowalczykowski andhis colleagues arehoping to harness theprocess for medicalpurposes, includinggene therapy and ultra-precise delivery ofDNA-repairing drugpayloads.

“Our very simple goalwas to see in real time amolecular motor runningalong a strand of DNA,something that has neverbeen visualized before,”Kowalczykowski said.

It took a combinationof sophisticated toolsand custom engineer-ing to make the DNAstretch out sufficiently

and hold still long enough to be photo-graphed while the enzyme moleculeswere attached.

Lighting was provided by special fluores-cent dyes that make DNA glow when it isin its typical double-stranded form, butnot when the molecule has been un-zipped into two single strands.

Glowing polystyrene beads were attachedto one end of each piece of DNA to helpanchor them down. The researchers alsowielded laser beams as pairs of high-precision “optical tweezers” to help keepthings under control.

A single helicase molecule, attached to aDNA molecule, was then loaded into onechannel of a Y-shaped micromachined“flow cell.” The action began when theATP was added as fuel through the otherarm of the “Y.”

At that point, the video camera beganrecording the scene through an opticalmicroscope, capturing the glowing DNAas the enzyme molecules marched alongtoward the polystyrene anchors.

The enzyme molecules are too small to beseen one at a time, even under the

Clip zips to No. 1. Professor of microbiology Stephen Kowalczykowski (above); RonaldBaskin, professor of molecular and cellular biology, and post-doctoral researcher PieroBianco produced a film that shows the enzyme helicase unwinding strands of DNA. In lateJanuary, when the film was placed on the San Francisco Chronicle’s Web site,www.sfgate.com, it was clicked on more times than any other picture or video file.

(above) A series of "stills" taken from video tape of theenzyme helicase (large round spot) unwinding DNA. The filmtook nearly four years to complete.

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WINTER 2001 3

FIRST FLOWERING PLANTGENOME SEQUENCED

The first complete genome sequencefor a flowering plant, Arabidopsisthaliana, was published on Dec. 14

in the journal Nature. Anne Britt,professor in the Section of Plant Biology,contributed to the report.

Arabidopsis is a small, fast-growing plantwidely used in plant biology research.The completed genome sequence mayopen up ways to study human diseasesusing plants.

The researchers found unexpectedsimilarities to, and differences from, otherorganisms that have been sequenced,such as the yeast Saccharomyces cerevisiae,the fruitfly Drosophila, and the soilroundworm Caenorhabditis elegans.

microscope. And technical problems madeit impossible to use more advancednanotech imaging methods that makepictures by recording subtle atomic forces.

So the researchers had to settle for theindirect strategy of the special dye. As theenzyme unzipped the DNA into its twoseparate strands, the light appears toblink out in the enzyme’s wake. Thepictures show the DNA strands seem-ingly growing shorter and shorter.

In the end, only the polystyrene bead isstill visible, even though the unlit DNAstill dangles in place.

Kowalczykowski said additional experi-ments are planned to better understandhow the enzymes work at the level ofindividual molecules—activity thatbiochemists traditionally have studied bymixing test tubes and beakers containingmolecules by the millions.

Looking at a single molecule as itchanges form is “a very powerfulapproach,” Kowalczykowski said. “If youwant to know how a car works, you cantake an aerial view of Interstate 80 andsee thousands of cars at once, which cantell you something,” he said. “But if youreally want to understand how a carworks, eventually you have to take aclose look at a single car.”

Teams of scientists examined the DNAsequence for genes with particularfunctions. Britt, in collaboration withJonathan Eisen of The Institute forGenome Research, looked for genes thatrepair damaged DNA.

“Twenty-seven genes were identified inArabidopsis that were closely related tohuman disease genes,” said Britt. Ofthese, a third were DNA repair genes,including genes linked to some types of

breast and colon cancer, and to thehereditary disease xeroderma pigmentosa,which makes children extremely suscep-tible to skin cancer.

“Arabidopsis has a similar distribution ofrepair genes to humans. Arabidopsismight turn out to be a very good modelfor the study of DNA repair in mam-mals,” said Britt.

UC Davis has established a nationalpresence in the study of DNA repair andchromosome biology, according toStephen Kowalczykowski, director of theCenter for Genetics and Development.

MICROBIOLOGISTSPLUMB THE DEPTHS

A remote-controlled submarine isbeing used to study mysteriousbacteria living half a mile below

the surface of Monterey Bay. UC Davismicrobial ecologist Doug Nelson,professor in the Section of Microbiology,

The first complete genome sequence for a flowering plant, Arabidopsis thaliana,was published on Dec. 14 in the journal Nature. Anne Britt (above), professorin the Section of Plant Biology, contributed to the report.

leads the research.

The team uses a remote operatedvehicle (ROV) owned and operated bythe Monterey Bay Aquarium ResearchInstitute (MBARI). The ROV Ventanais equipped with high-definitioncameras and laser measuring equip-ment, and its arms can be fitted witha variety of collecting and samplingequipment.

Because of their strange andhostile habitat, deep-seabacteria have evolvedsurvival strategies foundnowhere else on Earth. Farfrom the sun, they live onhydrogen sulfide seepingfrom cracks in the seafloorand use nitrate in seawaterinstead of oxygen.

One example is Thiomargaritanamibiensis, giant bacteria thatgrows to almost a millimeterin size—100 times the size ofany other known bacterium.Thiomargarita was discoveredin 1999 in deep water off thecoast of Namibia in southern

Africa, by a team led by German scientistHeide Schulz.

This year, Schulz will join the UC Davisresearchers studying bacteria aroundsulfide seeps in Monterey Canyon.Nelson’s lab is particularly interested inBeggiatoa, bacteria that grow in longfilaments on the seafloor mud.

Although these bacteria are deep in theocean, they can be affected by fertilizerrunoff, aquaculture and dumping ofwaste at sea, said Nelson.

“If you insult the ocean in a significantway, it will result in a die-off,” saidNelson. That could lead to a release ofhydrogen sulfide from the seafloor, whichcould affect fish and other marineanimals and plants.

Website: http://www.mbari.org/dmo/ventana/ventana.html.

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4 WINTER 20014 WINTER 2001

BY KATHLEEN HOLDER

Botany Professor Emeritus John Tucker, whoplayed a leading role in developing UC Davis’herbarium and arboretum, is helping to ensure thefuture health of both facilities with a $500,000 gift.

The money will be divided equally between theherbarium and arboretum, enabling each, amongother things, to maintain world-class collections ofoaks—trees that have been the subject of Tucker’sintellectual passion for most of his life.

The arboretum’s share will establish the John M.Tucker Oak Collection Endowed Fund to maintainits oak trees, particularly those in the Peter J.Shields Oak Grove. The grove contains more than80 kinds of oaks, many of them grown from acornscollected for Tucker from throughout the UnitedStates and northern Mexico as part of his research.

The portion for the herbarium is the first major gifttoward construction of a $3 million state-of-the-artfacility to house its more than 200,000 dried plantspecimens. Many of those specimens, including anextensive oak collection, were acquired during the39 years Tucker directed the herbarium.

The new herbarium will be located in thefuture Sciences Laboratory Building, which isslated to open in mid-2004 east of the LifeSciences Addition.

Solid as an OakThe herbarium’s $2 million costs are part of an$8.5 million “Opportunities for Distinction” fund-raising campaign by the Division of BiologicalSciences. The College of Agricultural and Environ-mental Sciences, which jointly administers theherbarium with the biological sciences division, isalso raising private funds for the facility.

Tucker, 85, said he had been considering givingsuch a gift for a number of years.

“I’ve been interested in these two facilities myentire career, since the very beginning,” Tuckersaid. “Both of them, at least in the early years, havehad tough-going financially. Things have changedin recent years very much for the better. I justwanted to help things along.”

Tucker joined the UC Davis faculty and beganoverseeing the Botany Herbarium in 1947 while hewas completing his research for his Ph.D. fromUC Berkeley. He received his degree three years later.

When he started at the herbarium, the specimensnumbered fewer than 10,000. During his tenure,he started an exchange program and vastlyexpanded collections of weeds and California flora,as well as oaks. By the time he retired in 1986, thefacility was renamed in his honor.

(In addition to the J. M. Tucker HerbariumCollection, the current UC Davis Herbarium alsoincludes the Beecher Crampton HerbariumCollection—known for its California nativegrasses—which was started in 1913 and movedfrom another campus location in 1988).

Tucker also became involved in the arboretum’sdirection early in his career, joining its administrativecommittee in 1953, filling in as acting director in1965-66 and serving as director from 1972 to 1984.

Ellen Dean, the herbarium’s director and curator, saidTucker’s gift is a demonstration of his “vision for anda true belief in the importance of the herbarium.”

“As director of the herbarium in 1960, Johndesigned our current herbarium space,” Dean said.“We will always remember that he stepped forwardfirst, when we needed to move beyond the spacethat he designed and into new facilities.”

Arboretum Director Kathleen Socolofsky saidTucker’s gift will “provide the critical resourcesnecessary to ensure the long-term health of the

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Botany Professor Emeritus John Tucker says he hopes his $500,000 gift willhelp ensure a financially secure future for the herbarium and arboretum.“I’ve been interested in these two facilities my entire career,” he says.

Retired professor’s gift to benefit herbarium and arboretum

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WINTER 2001 5 WINTER 2001 5

oaks and to fund educational and interpretiveprograms relating to the Shields Oak Grove.

“Dr. Tucker’s gift is especially meaningful becauseof his role in developing our outstanding oakcollection and because of his strong leadership asarboretum director in the 1970s and 1980s.”

An authority on oak hybrids, Tucker said hedeveloped a fascination for the stately trees whileparticipating in scouting activities as a teenager inSanta Barbara in the 1930s.

With little money during the Depression for otheractivities, his scoutmaster took him and othermembers of his Boy Scout troop on weekend hikesand camping trips where they learned to identifythe local trees and shrubs.

About the same time, the local natural historymuseum had an exhibition on oaks native to SantaBarbara County. “I was amazed to see how manydifferent kinds there were. So I went back repeatedly.”

Tucker said he pestered the curator into telling himwhere the different varieties grew. “It wasn’t toolong before I found myself hitchhiking to placeswhere I could see these oaks.”

On his longest trip, when he was about 16, hehitchhiked nearly 120 miles to the foothills of theSan Gabriel Mountains in northern Los AngelesCounty to see the southernmost grove of Oregonoak. A forester who drove him the last leg of thetrip in his pickup truck became a lifelong friend.

Tucker was the third of eight children born to afarming family in the tiny western Oregon com-munity of Amity. His family moved to Ithaca, N.Y.,when he was a toddler, then settled in SantaBarbara when he was four.

After graduating from high school in 1934, heenrolled at what was then Santa Barbara StateCollege (now UC Santa Barbara). He transferred asa junior to UC Berkeley where he graduated withhonors in 1940.

He entered graduate school at UC Berkeley, wherehe studied under the likes of G. Ledyard Stebbins,a pioneering plant evolutionist who would joinUC Davis not long after Tucker.

World War II interrupted Tucker’s doctoral studies.With poor eyesight keeping him from enlisting, hewent to work as a machine welder for a Navalshipyard in Richmond. Later, he worked for a ShellOil research plant in Emeryville as an overnightlab monitor, checking on chemists’ experiments,until his major professor persuaded him to returnto graduate school. He did even though it meantsacrificing his $200 monthly salary to earn $95 amonth as a teaching assistant.

He and his wife, June, a fellow UC Berkeleygraduate and the only child of a bank vice presi-dent, moved to Davis in 1947 while June wasexpecting the first of their three children.

Tucker joined the faculty of what was then the BotanyDepartment and is now the Section of Plant Biology.

His research focused on taxonomy of oaks andintermingling of oak species. “Oaks have a longreputation of being a difficult group to classifytaxonomically. They’re horrendously variable, soit’s hard to draw a line from where species A startsoff and species B begins.”

Tucker shares an office near the herbarium and stillconducts research. However, he said he no longerapproaches it with the same single-minded intensityas he did before his wife died of cancer in 1987.

Other interests also occupy his time, he said. A self-described newspaper addict, he reads three newspa-pers daily as well as a number of other publications.He also has traveled to China, Central America,Scandinavia and Russia since retiring.

“There’s no question I’m slowing down. The desireis still there but my research has tapered off.”

However, directors of the herbarium and arbore-tum said Tucker’s gift will ensure a long-lastinglegacy for his many contributions to a betterunderstanding of oaks and other plants.

Oak trees in the arboretum (above) will benefit from John Tucker’s gift, partof which establishes the John M. Tucker Oak Collection Endowed Fund.

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6 WINTER 2001

of technological evolution rendering aclass obsolete. “In 1990, we offered aclass in alternatives to radioactivelabelling, which were newly developed,”she says. “The health, environmental,disposal and monetary costs of usingradioactive labels had become apparent,and I felt it was important to introducethese techniques.” Today the techniquesare standard, and the course isn’t offeredseparately, its content having beenincorporated into the biotechnologyprogram’s other classes.

Enter polymerase chain reaction (PCR), atechnique used to make numerous copies

of a specific segment of DNA quickly andaccurately.

“By the early 1990s, PCR was reallytaking off,” says McGloughlin. “I con-tacted someone I knew at Perkin-Elmer,who was willing to provide equipmentand teach a class.”

McGloughlin continues, “We still offer anadvanced PCR class and it’s one of themost highly subscribed to. We constantlyupdate it because the technology isconstantly evolving.” She laughs as sherecalls that a few years ago severalemployees from Chiron, a biotechnologyfirm, attended the class. “"The Chiron

employees were essentially coming fromwhere PCR originated because Chirontook over Cetus, the company thatinvented PCR. So it was funny that theycame here to learn the technique.Apparently people in the company weresimply too busy to teach the technique.”

She adds, “We offered in situ PCR fortwo years, but the technique was sosystem-specific and temperamental thatit didn’t lend itself to a generic labcourse. A course on carbohydrateresearch didn’t garner enought interestto warrant the time and energy involvedin offering it. So in addition to coursesthat became obsolete, courses that justdidn’t work out have been a part of theprogram’s growth.”

McGloughlin then took theinitiative to discover whattype of biotechnologyinstruction was needed.

“I thought we should offer aprotein analysis class,” saysMcGloughlin, “although thefirst time we offered it notmany people enrolled. Sincethen people have movedfrom genomics to proteomics[quantifying all the proteinsexpressed at any given timein a cell] and the enrollmenthas increased. The class hasalso evolved from basicprotein analysis—isolation,purification, and character-

ization—to true proteomics using 2-D gelanalysis and advanced mass spectometry.We teach the class in conjunction with theUC Davis Molecular Structure Facility,which helps familiarize people with thepowerful technology that’s available on thiscampus.”

A burgeoning new discipline motivatedMcGloughlin to expand course offeringsin 1995-96. “It became clear to me thatwe needed to focus on bioinformatics,which addresses how to electronicallystore, organize, and access the massivedatasets being generated in the lifesciences,” says McGloughlin. “For so long

...BIOTECH SCHOOL

(continued from front page)

biologists went into biology because theywere math averse—we can’t afford to bethat way any longer.”

The initial bioinformatics course was asurvey course and McGloughlin discov-ered it wasn’t focused enough.

“For the bioinformatics course we had ahuge spectrum. At one end werebiologists who wanted to know some-thing about bioinformatics but didn’twant to know what happens inside theblack box; they didn’t want to knowhow to program computers. At the otherend were the computational people whowanted to know more about biology,and then there was a whole bunch ofpeople in the middle who wanted toknow a bit of both.” In 2001,McGloughlin therefore split up the onebioinformatics class into two sections,each of which covers a different aspectof the subject.

Overall the fast-paced courses receiveexcellent evaluations. “The content of thecourses usually challenges the students,”says McGloughlin, “and often they learnmore than they had expected to.” Shelaughs again as she says, “A woman in theprotein analysis class said her head hurtafterward, but she gave us a greatevaluation.”

Depending on pre-enrollment,McGloughlin plans to offer the followingcourses in summer 2001:

❿ In Situ Diagnostics and Analysis

❿ Confocal Microscopy

❿ Advanced Polymerase Chain ReactionTechniques

❿ Bioinformatics I: Instrumentation andBiological Samples

❿ Bioinformatics II: Databases, Visual-ization, Data Mining and Integration,Algorithms and Image Processing

❿ Protein/Proteome Analysis

Information about enrollment, costs, andcourse content is available at http://www.biotech.ucdavis.edu/courses/new_courses.htm.

Martina McGloughlin (above), director of UC Davis’ Biotechnology Program, isaware of only a few other places in the United States that offer classes similar tothe Biotechnology Program’s courses.

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F O C U S O N F A C U L T Y

CARL SCHMID:A STORY WITHREPETITIVE ELEMENTS

The Christmas he was 7 years old,Carl Schmid was walking with hisfather when he spied a shiny

chemistry set displayed in a storewindow. Schmid asked if he could havethe set; his father replied, “No, you haveto become a chemist to have that.” Theyounger Schmid immediately thought,“Then I’ll become a chemist.”

His resolve never wavered.

“Chemistry was my childhood hobby,”Schmid says. “I set up a home lab and cutgrass to buy chemistry sets. My friendsand I made explosives and concocted ourown experiments. It’s something I reallywanted to do.”

As an undergraduate, Schmid attendedDrexel Institute, Philadelphia, Pa., wherestudents attend school for six monthsand work for six months. His job notonly made college affordable, but alsoexposed him to the research that wouldbecome a primary interest. “I was placedin a laboratory and became interested innucleic acids, an interest that led me topursue my doctoral studies under JohnHearst, who was studying DNA structureusing physical methods, at UC Berkeley.”

After receiving his doctorate in biophysi-cal chemistry in 1971, Schmid took apost-doctoral position at CaliforniaInstitute of Technology in Pasadena,where he became interested in studyingeukaryotic genome structure at a timewhen sequencing and cloning techniqueshad not yet been developed. He contin-ued his post-doctoral studies at UC Davis“with the idea,” says Schmid, “that I’dstudy the structure and organization ofthe human genome using physicalmethods developed at Cal Tech.”

Schmid became a faculty member inUC Davis’ Chemistry Department in1973. His research on DNA structure led,

in 1990, to a joint appointment in thechemistry department and Department ofGenetics (now the Section of Molecularand Cellular Biology).

Since the late 1960s scientists had beenaware that the eukaryotic genome

contained repetitive DNA sequences. Theprevailing theory was that many distinctfamilies composed the repetitive DNA,each distinct family having a few thou-sand members interspersed throughoutthe genome.

Careful analyses carried out by Schmidand his laboratory revealed, in 1979, asituation very different from the prevail-ing theory: a major fraction of therepetitive sequences belonged to a singlefamily—the Alu family, which appearedto constitute about five percent of thehuman genome.

Walter Eckhart, a molecular biologistwith The Salk Institute, noted in 1981,“His [Schmid’s] recent work on inter-spersed sequences in the human genomehas been a major contribution to a

particularly interesting and importantarea of modern genetics. It has won himinternational recognition and has helpedto advance the work of many others inthe field.”

Most scientists believed the ubiquitousAlu repeats were purposeless—alongwith other types of DNA sequences thatdon’t code for genes, they fell under therubric “junk DNA”—but in 1998 Schmidproposed the controversial theory thatAlu repeats are activated when cells aredamaged in some way, for example byheat, toxic compounds or lack of essen-tial nutrients, and help repair damage bycontrolling genes that make proteins.

“We found that these repeating elementsare expressed, normally at very lowlevels, but when a tissue is stressed, theirexpression increases,” says Schmid.

The recent publication of the humangenome maps stimulated a reexaminationof Schmid’s hypothesis.

“There’s tremendous excitement now thatthe genome has been sequenced,” saysSchmid, “and it’s been observed that Alurepeats are extremely abundant through-out the genome, and are often found neargenes that code for proteins.”

In fact, the maps show that Alu repeatsmake up 10 percent of the genome—twice as much as was previously sup-posed.

In regard to the widespread presence andstrategic placement of Alu repeats,Francis Collins, director of the NationalHuman Genome Research Institute, wasquoted in a New York Times article assaying, “…the natural conclusion is, thispart of our junk DNA isn’t junk.”

Schmid comments, “I can’t say at thispoint that my theory is right or wrong,but the new genome maps certainly haveintensified interest in my laboratory’sresearch.”

Prescott Deininger, Zimmerman Chairfor Cancer Research at Tulane University’sSchool of Public Health and Tropical

Carl Schmid (standing) and his colleagues discovered, in1979, a family of repetitive DNA sequences. Known as “Alurepeats,” these repetitive sequences were characterized as“junk DNA.” However, the recently published human genomemaps revealed that Alu repeats constitute 10 percent of thegenome and are located near genes. These findings havecaused scientists to reexamine Schmid’s controversial theorythat the Alu repeats aren’t junk DNA but are activated inresponse to cellular stress.

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8 WINTER 2001

P E O P L E

1996

Kevin A. Morano, Ph.D. Microbiology,1996, is currently an assistant professorin the Department of Microbiology andMolecular Genetics at the University of

Texas MedicalSchool in Houston.

He conducted hisdoctoral research inProfessor DanielKlionsky’s labora-tory (Klionsky ispresently with theUniversity ofMichigan) studyingtargeting and

assembly of vacuolar proteins. He contin-ued his education with postdoctoral

ALUMNI

studies in the Department of Biochemistryat the University of Michigan MedicalSchool (1996-2000), studying yeast stress-response mechanisms.

Morano is currently studying the func-tions of a class of proteins called “mo-lecular chaperones,” which help proteinsfold in the cell. Many important cellularregulatory proteins are very unstable andrequire a protein chaperone called Hsp90to protect them. Says Morano, “Mylaboratory is interested in how the cell inturn regulates the function of thechaperones themselves. We’re also usingthe latest in DNA microarray technology

to identify new stress genes in the modeleukaryotic cell Saccharomyces cerevisiae,or baker’s yeast. Many of these genes haveclose human homologs, and by studyingthe genes in yeast, we may learn abouthow they are recruited for ‘stressful’pathological states in our own cells, likecancer and aging.”

1992

Jason Bradford, B.S., BiologicalSciences, 1992, received his Ph.D. inevolutionary and population biologyfrom Washington University, St. Louis,Mo. Says Bradford, “My current positionis research associate at the MissouriBotanical Garden in St. Louis. I’m also acourse instructor in ecology at Washing-ton University.

“I was traveling in New Caledonia, inDecember 2000, on a grant from theNational Geographic Society to study thesystematics and pollination biology of afamily of flowering plants, Cunoniaceae,that I specialize in. Along with me wasBarry Donovan from New Zealand, whoknows more about pollination biologythan I do, and is an expert on the bees ofNew Caledonia. Barry received hisdoctorate from UC Davis in 1969 inentomology.

“While staying in a small motel in thenorthern town of Koumac, Barry and Imet Mike Irwin. It turns out that Mike

WINTER 2001 8

Three UC Davis graduates in New Caledonia having breakfast at their motel, Le Grand Cerf, which means “the big deer.” Fromleft to right: Mike Irwin, Jason Bradford, Barry Donovan.

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...SCHMID

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Medicine, New Orleans, La., also studiesAlu repeats and was a graduate researchassistant in Schmid’s laboratory from1974 to 1978.

Says Deininger of Schmid’s research, “Therecent focus on the sequence of thehuman genome has really highlighted theincredible role that Alu has played inshaping the human genome.

“Carl has been one of the major contribu-tors to the characterization of this type ofelement for over 25 years. In recent yearshis has been the major laboratory in theworld focusing on the quest for possiblefunctions of those elements. He’s arigorous and imaginative scientist.”

According to Schmid the new genomemaps will lead to more studies of howAlu repeats influence genes.

“Until we resolve the question of whetherthese sequences are junk, or have adefined function, it’s impossible tounderstand the evolution of genomestructure,” he says.

Kevin Morano

We welcome newsfrom alumni for the

“People” section;please

e-mail the editor [email protected].

Or visit the alumniWeb site at

www.dbs.ucdavis.edu/alumni/postcards/

and send us apostcard.

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WINTER 2001 9

was there to study a group of flies he isdoing a worldwide monograph on, andhe also graduated from UC Davis—with aB.S. in entomology in 1963. He also has aPh.D. in entomology from UC Riversideand is currently a professor at Universityof Illinois.

“My wife Kristin Bradford (néeSparks) also graduated from UC Davisin 1992 with a B.S. in physiology. Shewas the division’s first student com-mencement speaker. She now has amedical degree from University ofVermont and is finishing her residencieshere in St. Louis (family practice andpreventive medicine). We plan to moveback to Davis in July 2001 with our twinboys, Curtis and Davis, who will be 2 1/2years old by then.”

FACULTY

The Botanical Society of Americaawarded its 2000 Merit Award, its highesthonor, to Leslie Gottlieb, a professor inthe Section of Evolution and Ecology. Anannouncement in Plant Science Bulletin,the society’s newsletter, described Gottliebas “one of the most influential plantevolutionary biologists over the pastseveral decades.” The award committeechair, University of Wisconsin geneticsprofessor John Doebley, cited three ofGottlieb’s publications as classics,including a 1984 article in AmericanNaturalist that “has been called one of themost important papers in plant evolu-tionary biology during the past halfcentury.” However, Doebley added thatGottlieb’s “greatest contribution may havecome through his influence on thecareers and research of a substantialnumber of plant evolutionary biologists,including many of the people most activein this field today.”

IN MEMORIAM

UC Davis exercise biologist PaulMolé, whose research contributed toan understanding of how musclesfunction during exercise, died onJanuary 20 of complications following

a heart attack. He was 62.

Molé became ill on Jan. 8 while teachinga class. Thanks to prompt action by histeaching assistants, he was taken to SutterMemorial Hospital and later transferredto the UC Davis Medical Center inSacramento. Although doctors were ableto remove a blood clot from a coronaryartery, his condition deteriorated, and hedied early Saturday morning.

Molé’s main research interest was inskeletal muscle metabolism, and howit responds to exercise, said UC DavisProfessor Emeritus Ed Bernauer, afriend and colleague for more than40 years.

“He reanalyzed much of the importantdocumented research, and formulated amathematical model that challenged theaccepted view,” said Bernauer. While theconventional view held that carbohy-drate, not fat, was the primary fuel formuscles, Molé believed that fat played agreater role earlier in exercise, accordingto Bernauer. He then went on to test hisideas using magnetic resonance imaging(MRI) techniques.

“He’ll be sorely missed,” said Tom Jue,a biochemist in the School of Medicinewho worked closely with Molé. UsingMRI technology developed in Jue’slaboratory, they could look inside anathlete’s limb to see how the musclesused oxygen and fuel during exercise.As a physiologist with expertise inmuscles, Molé’s contribution was veryimportant in helping to develop thetechnology, said Jue. Eventually, thesame technology might be used tostudy heart disease, he added.

Molé was vice chair of the Department ofExercise Science and held an adjunctappointment at the Department ofPhysical Medicine and Rehabilitation. Hewas a faculty member of the graduategroups in exercise biology, nutrition andphysiology.

Molé played a pivotal role in the recentrestructuring of the exercise biologyprogram, and was actively involved in

...PEOPLE

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recruiting new faculty, said departmentchair Chuck Fuller.

“We’re going to miss his insight as webuild for the future,” said Fuller.

“He was an intense and committededucator, who felt it was the obligation ofthe professor to bring students to thehighest level of understanding,” saidBernauer. “Paul was always challenginghis students, always pushing them tothink,” said Fuller.

Brought up in Jamestown, N.Y., Moléentered the University of Illinois, Urbana-Champaign, on a football scholarship,graduating in 1960. He stayed at Illinoisto complete a M.S. in physical educationand a Ph.D. in physiology. He joinedUC Davis in 1977.

Molé was a Fellow of the AmericanCollege of Sports Medicine, and amember of the American PhysiologySociety and the New York Academy ofScience. He served as president of theSouthwest chapter of the American Collegeof Sports Medicine from 1999 to 2000.

Molé loved the outdoors, whetherwalking in the woods, fishing or garden-ing, said his wife of 42 years, Patty. Hewas a keen amateur photographer. Hisparents were bakers, and he liked to bakeand cook, making fresh bread everyweekend, she said.

He is survived by Patty; their threechildren, Pam, of Oklahoma, Greg, ofPittsburgh in the Bay Area, andMichael, of San Jose; and five grand-children. In his freshman year on afootball scholarship, Molé told hiscoach that he was marrying Patty, hishigh-school sweetheart. The coach toldhim he could either get married or playfootball, but not both. Molé respondedby giving up football and taking upfencing, joining a team that went on towin the Midwestern Big Ten champion-ship, an achievement that typified hisdetermination and persistence, saidBernauer.

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10 WINTER 2001

“We’re moving into a time when we’ll need tointegrate our knowledge of genes with ourknowledge of proteins,” says Smietana.“Genes don’t mean very much without thecontext of proteins and vice versa. So thescope of your experiment has to change. Younow have to consider bringing in moreinformation than you ever have before. Thatmeans you’re going to have to learn some-thing about the tools that are out there. Astudent may study one protein for her doctoralresearch, but we now have the ability to studysets of proteins.”

When asked how undergraduates can preparethemselves for careers in bioinformatics,Smietana replied with a brief anecdote. “I wasrecently at a meeting with representatives fromGenentech, DoubleTwist, Applied Biosystems,and Iconics,” he says. “Asked for description ofan ideal candidate for a position inbioinformatics they responded, ‘A full professorin biological sciences with 20 years experiencein the computer field.’ We know that persondoesn’t exist, so how can you parlay that down?The best strategy for an undergraduate is to takea diverse program.”

And remember: think big.

DIVISION OFBIOLOGICALSCIENCES

UNDERGRADUATE MAJORS

BiochemistryBiological SciencesCell BiologyEvolution and EcologyExercise BiologyGeneticsMicrobiologyNeurobiology, Physiology, and BehaviorPlant Biology

GRADUATE PROGRAMS

Animal BehaviorBiochemistry and Molecular BiologyBiophysicsCell and Developmental BiologyExercise ScienceGeneticsMicrobiologyNeurosciencePhysiologyPlant BiologyPopulation Biology

SECTIONS

Evolution and EcologyMicrobiologyMolecular and Cellular BiologyNeurobiology, Physiology, and BehaviorPlant Biology

UNIVERSITYWIDE AND

CAMPUSWIDE PROGRAMS

Biotechnology ProgramCenter for Animal BehaviorCenter for NeuroscienceCenter for Population BiologyUC Life Sciences Informatics Program

Published by theDivision of Biological SciencesUniversity of CaliforniaOne Shields AvenueDavis, CA 95616-8536Phone (530) 752-6764Fax (530) 752-2604http://www.dbs.ucdavis.edu/

Debra Cleveland, [email protected] Forrest, Campaign ManagerKathleen Holder, Manager of CommunicationsMark McNamee, DeanThomas Rost, Associate DeanDonna Olsson, Executive Assistant DeanJacqueline Schad, Director of Development & External RelationsEllen Tani, Assistant Dean

RECYCLED • RECYCLABLE

O n e S h i e l d s A v e n u eD a v i s , C A 9 5 6 1 6 - 8 5 3 6

...BIG PICTURE

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Smietana supported himself by programmingcomputers. He thus possesses both biologicaland computational perspectives. Smietana hasbeen associated with the biotechnology industryfor more than 18 years; while with CiphergenBiosystems and GeneLogic he created novelmethods for integrating protein and DNAexpression data with public and private clinicaland genomic databases. For the past three years,he has taught the summer bioinformatics shortcourses.

Underscoring the need to think big, Smietanatalks about the direction in which the lifesciences industry is headed. “I want students tobe aware of the scaling up of technologies inindustry,” he says. “As an example, LumiCyte isgoing to have 20, perhaps 30 or 40 instruments,with multiple sites throughout the world,collecting information on proteomic biochips.Again, the amount of information is staggering—we’re talking about terabytes of information.”

According to Smietana, what this translates intois a need for people who know how to designcomplicated, integrated experiments.