Current Biology Vol 15 No 19R780

It is a rare twenty-first centurybiologist who hasn’t foundthemselves at some pointdreaming of a simpler, lessadministrative, more collegial timein research. For some, that dreammay entail a trip back to the1950s, when early molecularbiology hooligans shook eachother down for ideas in the pubsof Cambridge. But for HowardHughes Medical Institute, thedream lies in the near future and isembodied in their ambitiousJanelia Farm researchlaboratories, set to open doors inthe summer of 2006. With the firstround of appointments now made,the scientific nexus of thelaboratories has begun to takeshape, enlivened by a good dealof enthusiasm and energyexpressed by the newly appointedlab heads.

Intended as haven for topresearchers drawn from differentfields, Janelia Farm is perhapsdistinguished from other large-

scale interdisciplinary endeavorsby the decision to establish at theoutset some specific problems onwhich to focus research efforts.2004 marked an intense series offive workshops whose goal wasfinding a suitable focus for thenew labs. Two related problems —understanding neural circuitry,and developing cellular imagingtechnology — beat out stiffcompetition in other fields,including topics in membranebiology, perception and behavior,and cellular biochemistry.

The development of the free-standing research campus marksa distinct departure for HHMI,which has historically fulfilled itsresearch mission primarily throughthe appointments of individualinvestigators who carry outHughes-funded research at theirhome institutions. The Janeliacampus, once built and fullystaffed, is envisioned to include 20to 30 group leaders and apermanent research staff of about

300 scientists. Joint graduateprograms with the University ofCambridge and the University ofChicago will allow PhD studentsto participate.

Gerry Rubin, HHMI VicePresident and Director of JaneliaFarm, says that when the projectwas first envisioned, Hughes waslooking to make a qualitativechange in the Institute’s impact.At the time, money was availableto fund 50 more Hughesinvestigators — which at a recentpeak already numbered nearly 450– and the NIH budget wasdoubling. Rubin characterizesthose early discussions, whichincluded HHMI Chief ScientificOfficer David Clayton, andPresident, Tom Cech, as a thoughtexperiment on what could bedone with Hughes resources thatwould have more impact — andwould be more useful — forbiomedical research than justhaving 50 more investigators.According to Rubin, “that was thebeginning. Janelia Farm was theanswer to that question.”

Janelia Farm represented forRubin and colleagues theopportunity to create the kind ofresearch environment that hadfacilitated great advancements inthe past — an environment thatthey recognized was todayvanishing, especially in the U.S.Their inspirations werecollaborative, interdisciplinaryresearch hothouses of the pastand present — places like BellLabs, Cold Spring Harbor Labs,EMBL, and perhaps mostprominently, the storied MRCLaboratory of Molecular Biology— places that produced some ofthe foremost work in science inthe last century, in large part, thethinking goes, thanks to the richlysupported but non-constrainingenvironments they providedresearchers.

This summer, the who and whatof Janelia Farm has begun to takefurther shape with the naming ofthe first round of group leaders.

Features

Farming for new opportunities

The Howard Hughes Medical Institute has departed from its tradition ofprimarily funding investigators in their home institutions by developing abrand new campus which it hopes will foster new research possibilities.Heather Dawes reports.

A farm like no other: Construction is now under way in suburban Virginia for theJanelia Farm campus for the Howard Hughes Medical Institute, which will provide38,000 square feet of laboratory space. Details above are from an artist’s impression ofthe main laboratory building. (Picture: Rafael Viñoly Architects.)

The appointees, the first sevenmembers of what will become aconsiderably larger collection ofgroup leaders, are Karel Svobodaand Dmitri Chklovskii, both ofCold Spring Harbor Laboratory;Nikolaus Grigorieff of BrandeisUniversity; Sean Eddy ofWashington University School ofMedicine; Eugene Myers of theUniversity of California, Berkeley;Julie Simpson of the University ofWisconsin, Madison; and RolandStrauss of the University ofWürzburg.

Slated to make the move toJanelia next summer, thesebehavioral geneticists, imaginggurus and computer scientists arenow in what seems to be a headypreamble stage, thinking aboutlong- and short-term goals,weighing potential collaborativepossibilities, and making contactwith each other.

Karel Svoboda and DmitriChklovskii already have anestablished and fruitfulcollaboration at Cold SpringHarbor working on imaging andmodeling neural circuitry — onethat will doubtless continue full-steam at Janelia. But, as Svobodarecounts, they now suddenly findthemselves joined in conversationwith computer scientist GeneMyers: “the person who madeshotgun sequencing work isactually now working on imageprocessing and how it relates toneurobiology.” They’ve startedcollaborative discussions wellahead of the physical move.

Svoboda points out that only asmall number of group leaderslots have been filled, and that heexpects additional collaboratorsto come on board in due course.Multiple alliances will no doubtcome in handy given the toughproblems at hand. Svoboda, apioneer in imaging neuralprocesses in the intact brain, andwho did critical work on imagingtechnology at Bell Labs, isparticularly interested in plasticneural processes and imaging thefunction of assemblages ofneurons in awake mice, even overthe long time courses relevant forprocesses such as learning.Svoboda acknowledgeschallenges in getting the neededtools — the appropriate sensors,

new imaging technologies, etc. —but feels that on a five-year timescale, the goals will beachievable. Beyond that, hissense is that once you have agood imaging paradigm working,you become situated to answersome of the key questions insystems neuroscience. “How aredecisions made in the brain? Howare memories formed andretrieved? Stuff like that wouldthen become much moreaccessible.”

As for Myers, the aims of thenew lab represent an opportunityto take the masses of dataproduced by high-throughputmicroscopy and find a way tomine that complex information forbiological meaning. His intereststems in part from a revelationexperienced a few years ago whiletraveling with a colleague inGermany, where he came acrossan impressive biotech set up forserial immunofluorescencemicroscopy. “I had a littleepiphany that microscopy in thenext ten or fifteen years was goingto become a major focus inmolecular biology, and is ripe togo high-throughput.”

“In my space, in bioinformaticsspace, a lot of people arepursuing things like expressionarrays, yeast two-hybrid systems,mass spectrometry… and whilethey’re certainly interestingtechnologies, none of them deliverthe kind of quality of data and theaccuracy that I think is necessaryto move molecular biologyrapidly.” Myers had the realizationthat whenever he read a high-profile paper, the compellingevidence was usually visual. “It’salways a picture… that’s howpeople are making hypothesesabout what’s going on.”

Clearly, it’s the compellingnature of images that inspiresMyers as he contemplates work at

Janelia. “You know, I’m therebecause I think that the imagesthat you get off the microscopeare just cool — they are just somuch fun to look at and workwith, and it just really tickles mybrain. I just want to roll around inthe stuff — and that’s what I planto do.”

Janelia Farm’s ying/yangmandate for exploring neuralcircuitry and developing imagingtechnologies also make it anespecially appealing place forbehavioral geneticists, a numberof whom are among the firstgroup of appointees.

Julie Simpson, who has beenstudying the behavioral effects oftargeted disruption andupregulation of specific subsets ofDrosophila neurons, is lookingforward to continuing that workand taking it to the next levelusing imaging. “We certainly havea lot of different [transgenics] thatdo unusual behavioral things, andthe next step is to try to map all ofthe brain onto a commonreference standard and have thecomputer pick out correlations”between regions of expressionthat correspond to behavioraleffects, says Simpson. Sheexplains that based on priorexperience, the work’s specificcourse is difficult to predict.“Initially I thought I would look atmotor behaviors — which neuronsare capable of causing a seizure— and in the course of screeningfor that I ran into all kinds of otherinteresting behaviors. So I don’tknow yet what directions we’ll goin, and that’s actually exactly whyI want to go to Janelia – because Ithink I will have encouragementand opportunity to followwhatever I find.”

Simpson is also looking forwardto collaborations. “I got very luckybecause Roland Strauss iscoming, and he is a fabulous flyneurobiologist with a lot ofneuroanatomical experience, andgreat gadgets.” Simpson recallsher first acquaintance withStrauss, when she was a graduatestudent, at a time when Strausswas having flies walk on tinytreadmills in behavioral assays.Simpson hopes to be able tocollaborate on analyzing particularbehaviors with such novel

Magazine R781

The Janelia campus, oncebuilt and fully staffed, isenvisioned to include 20 to30 group leaders and apermanent research staffof about 300 scientists

Every now and then one crossespaths with someone who wasclearly born in the wrong century— an avid knitter, a lutist, orsomeone who will actually sitdown and write a letter. Theseanachronisms are harder to findin science, but they do exist. Infact, a small band of themrevealed themselves during aresearch cruise this summer tothe Arctic Ocean.

You might not think to look foran 19th Century scientist on abright red, 420-foot-longicebreaker. After all, the “Healy”is bristling with high-tech toys.There’s a remotely operatedsubmarine that can dive morethan 2500 meters beneath thewaves. The sub’s high-definitionTV cameras reveal in stunningdetail what’s crawling around onthe bottom of the sea. Scientistsaboard the ship also revel atdaily access to email, even inlatitudes so extreme that thecommunication pathway is alow-bandwith connection topolar-orbiting Iridium satellites.

But Bodil Bluhm from theUniversity of Alaska notes withirony that it takes this kind ofset-up to do the kind of scienceshe was born for. And that is toexplore the natural history of aworld that feels pretty wellrevealed by now. As Bluhmstood on deck one July day,sorting excitedly through a catchof sea-floor critters brought up ina trawl net, she remarked, “Iactually would like to have lived150 years ago in the earlyexplorer phase” of oceanexploration. Then she thoughtbetter of it. “I would probablyhave sat at home and waited formy sailor husband to come back,or something. It’s good I’m herenow.”

The Arctic Ocean is one of thefew places left on Earth whereyou can promise in your grantproposal that you will discoverspecies entirely new to science— and not have to worry abouteating your words. This 30-dayexpedition was designed as abiodiversity survey, looking ateverything from invertebratesthat cling to the bottom of icefloes, to graceful pelagic jellies,and benthic brittlestars thatsomehow thrive on the organic

instrumentation, as well as newmolecular tools, including a large-scale collection of transgenic flylines Rubin is planning to develop.

Among the first group ofappointees, computationalbiologist Sean Eddy perhapsstands out as one who was drawnto the essential idea of Janelia.Eddy was looking to have asmaller lab, with what hedescribes as “sort of the MRC andBell Labs kind of style,” thatwould suit his interests insoftware development and hisgroup’s mixture of theoretical andexperimental work.

“I was immediately attracted —even before they knew what theywere going to do at the Farm —when Gerry Rubin startedstanding up and saying ‘this is theculture that we’re going to build.’This was always my dream. I wentup to him after that first time and Isaid, ‘Gerry, I don’t even carewhat you people work on there, Iwant to be considered.’”

Though Eddy plans to initiallycontinue his current work oncomputational biology and non-coding RNAs, he feels a pull in thedirection of studying neuralcircuitry — a problem that heinitially set out to tackle in C.elegans as a postdoc at the MRC.“I do dream about getting backinto neurobiology… at JaneliaFarm I’m going to be surroundedby all these great neurobiologists,and I’ll just be able to soak it allin.” He has a special interest inwhat he sees as Sydney Brenner’s“original question” — how amodel organism like the wormintegrates everything fromsensory input to behavioraloutput.

Conveniently, Brenner will be aSenior Fellow at Janelia, alongwith former Bell Labs director andformer Lawrence BerkeleyNational Lab head Charles Shank.According to Shank, despite theirdifferent interests — Schank has abackground in chemistry and aninterest in optics — he andBrenner are proving that evenSenior Fellows enjoy branchingout. “I’ve had just an enormousgood time talking with Sydney andthe way he thinks about biologyand technology… I’ve learned agreat deal from Sydney already.

Current Biology Vol 15 No 19R782

Skirting around thin ice

Richard Harris drops in on anexpedition charting Arcticbiodiversity under increasingthreat from climate change.

Revelations: A survey of Arctic fauna adds to an understanding of the richness of thislittle-known and threatened ecosystem. (Photo: NOAA.)