The Howard Hughes Medical Institute has departed from its tradition of primarily funding investigators in their home institutions by developing a brand new campus which it hopes will foster new research possibilities. Heather Dawes reports. The Howard Hughes Medical Institute has departed from its tradition of primarily funding investigators in their home institutions by developing a brand new campus which it hopes will foster new research possibilities. Heather Dawes reports. It is a rare twenty-first century biologist who hasn’t found themselves at some point dreaming of a simpler, less administrative, more collegial time in research. For some, that dream may entail a trip back to the 1950s, when early molecular biology hooligans shook each other down for ideas in the pubs of Cambridge. But for Howard Hughes Medical Institute, the dream lies in the near future and is embodied in their ambitious Janelia Farm research laboratories, set to open doors in the summer of 2006. With the first round of appointments now made, the scientific nexus of the laboratories has begun to take shape, enlivened by a good deal of enthusiasm and energy expressed by the newly appointed lab heads. Intended as haven for top researchers drawn from different fields, Janelia Farm is perhaps distinguished from other large-scale interdisciplinary endeavors by the decision to establish at the outset some specific problems on which to focus research efforts. 2004 marked an intense series of five workshops whose goal was finding a suitable focus for the new labs. Two related problems — understanding neural circuitry, and developing cellular imaging technology — beat out stiff competition in other fields, including topics in membrane biology, perception and behavior, and cellular biochemistry. The development of the free-standing research campus marks a distinct departure for HHMI, which has historically fulfilled its research mission primarily through the appointments of individual investigators who carry out Hughes-funded research at their home institutions. The Janelia campus, once built and fully staffed, is envisioned to include 20 to 30 group leaders and a permanent research staff of about 300 scientists. Joint graduate programs with the University of Cambridge and the University of Chicago will allow PhD students to participate. Gerry Rubin, HHMI Vice President and Director of Janelia Farm, says that when the project was first envisioned, Hughes was looking to make a qualitative change in the Institute’s impact. At the time, money was available to fund 50 more Hughes investigators — which at a recent peak already numbered nearly 450 – and the NIH budget was doubling. Rubin characterizes those early discussions, which included HHMI Chief Scientific Officer David Clayton, and President, Tom Cech, as a thought experiment on what could be done with Hughes resources that would have more impact — and would be more useful — for biomedical research than just having 50 more investigators. According to Rubin, “that was the beginning. Janelia Farm was the answer to that question.” Janelia Farm represented for Rubin and colleagues the opportunity to create the kind of research environment that had facilitated great advancements in the past — an environment that they recognized was today vanishing, especially in the U.S. Their inspirations were collaborative, interdisciplinary research hothouses of the past and present — places like Bell Labs, Cold Spring Harbor Labs, EMBL, and perhaps most prominently, the storied MRC Laboratory of Molecular Biology — places that produced some of the foremost work in science in the last century, in large part, the thinking goes, thanks to the richly supported but non-constraining environments they provided researchers. This summer, the who and what of Janelia Farm has begun to take further shape with the naming of the first round of group leaders. The appointees, the first seven members of what will become a considerably larger collection of group leaders, are Karel Svoboda and Dmitri Chklovskii, both of Cold Spring Harbor Laboratory; Nikolaus Grigorieff of Brandeis University; Sean Eddy of Washington University School of Medicine; Eugene Myers of the University of California, Berkeley; Julie Simpson of the University of Wisconsin, Madison; and Roland Strauss of the University of Würzburg. Slated to make the move to Janelia next summer, these behavioral geneticists, imaging gurus and computer scientists are now in what seems to be a heady preamble stage, thinking about long- and short-term goals, weighing potential collaborative possibilities, and making contact with each other. Karel Svoboda and Dmitri Chklovskii already have an established and fruitful collaboration at Cold Spring Harbor working on imaging and modeling neural circuitry — one that will doubtless continue full-steam at Janelia. But, as Svoboda recounts, they now suddenly find themselves joined in conversation with computer scientist Gene Myers: “the person who made shotgun sequencing work is actually now working on image processing and how it relates to neurobiology.” They’ve started collaborative discussions well ahead of the physical move. Svoboda points out that only a small number of group leader slots have been filled, and that he expects additional collaborators to come on board in due course. Multiple alliances will no doubt come in handy given the tough problems at hand. Svoboda, a pioneer in imaging neural processes in the intact brain, and who did critical work on imaging technology at Bell Labs, is particularly interested in plastic neural processes and imaging the function of assemblages of neurons in awake mice, even over the long time courses relevant for processes such as learning. Svoboda acknowledges challenges in getting the needed tools — the appropriate sensors, new imaging technologies, etc. — but feels that on a five-year time scale, the goals will be achievable. Beyond that, his sense is that once you have a good imaging paradigm working, you become situated to answer some of the key questions in systems neuroscience. “How are decisions made in the brain? How are memories formed and retrieved? Stuff like that would then become much more accessible.” As for Myers, the aims of the new lab represent an opportunity to take the masses of data produced by high-throughput microscopy and find a way to mine that complex information for biological meaning. His interest stems in part from a revelation experienced a few years ago while traveling with a colleague in Germany, where he came across an impressive biotech set up for serial immunofluorescence microscopy. “I had a little epiphany that microscopy in the next ten or fifteen years was going to become a major focus in molecular biology, and is ripe to go high-throughput.”The Janelia campus, once built and fully staffed, is envisioned to include 20 to 30 group leaders and a permanent research staff of about 300 scientists The Janelia campus, once built and fully staffed, is envisioned to include 20 to 30 group leaders and a permanent research staff of about 300 scientists “In my space, in bioinformatics space, a lot of people are pursuing things like expression arrays, yeast two-hybrid systems, mass spectrometry… and while they’re certainly interesting technologies, none of them deliver the kind of quality of data and the accuracy that I think is necessary to move molecular biology rapidly.” Myers had the realization that whenever he read a high-profile paper, the compelling evidence was usually visual. “It’s always a picture… that’s how people are making hypotheses about what’s going on.” Clearly, it’s the compelling nature of images that inspires Myers as he contemplates work at Janelia. “You know, I’m there because I think that the images that you get off the microscope are just cool — they are just so much fun to look at and work with, and it just really tickles my brain. I just want to roll around in the stuff — and that’s what I plan to do.” Janelia Farm’s yin/yang mandate for exploring neural circuitry and developing imaging technologies also make it an especially appealing place for behavioral geneticists, a number of whom are among the first group of appointees. Julie Simpson, who has been studying the behavioral effects of targeted disruption and upregulation of specific subsets of Drosophila neurons, is looking forward to continuing that work and taking it to the next level using imaging. “We certainly have a lot of different [transgenics] that do unusual behavioral things, and the next step is to try to map all of the brain onto a common reference standard and have the computer pick out correlations” between regions of expression that correspond to behavioral effects, says Simpson. She explains that based on prior experience, the work’s specific course is difficult to predict. “Initially I thought I would look at motor behaviors — which neurons are capable of causing a seizure — and in the course of screening for that I ran into all kinds of other interesting behaviors. So I don’t know yet what directions we’ll go in, and that’s actually exactly why I want to go to Janelia – because I think I will have encouragement and opportunity to follow whatever I find.” Simpson is also looking forward to collaborations. “I got very lucky because Roland Strauss is coming, and he is a fabulous fly neurobiologist with a lot of neuroanatomical experience, and great gadgets.” Simpson recalls her first acquaintance with Strauss, when she was a graduate student, at a time when Strauss was having flies walk on tiny treadmills in behavioral assays. Simpson hopes to be able to collaborate on analyzing particular behaviors with such novel instrumentation, as well as new molecular tools, including a large-scale collection of transgenic fly lines Rubin is planning to develop. Among the first group of appointees, computational biologist Sean Eddy perhaps stands out as one who was drawn to the essential idea of Janelia. Eddy was looking to have a smaller lab, with what he describes as “sort of the MRC and Bell Labs kind of style,” that would suit his interests in software development and his group’s mixture of theoretical and experimental work. “I was immediately attracted — even before they knew what they were going to do at the Farm — when Gerry Rubin started standing up and saying ‘this is the culture that we’re going to build.’ This was always my dream. I went up to him after that first time and I said, ‘Gerry, I don’t even care what you people work on there, I want to be considered.’” Though Eddy plans to initially continue his current work on computational biology and non-coding RNAs, he feels a pull in the direction of studying neural circuitry — a problem that he initially set out to tackle in C. elegans as a postdoc at the MRC. “I do dream about getting back into neurobiology… at Janelia Farm I’m going to be surrounded by all these great neurobiologists, and I’ll just be able to soak it all in.” He has a special interest in what he sees as Sydney Brenner’s “original question” — how a model organism like the worm integrates everything from sensory input to behavioral output. Conveniently, Brenner will be a Senior Fellow at Janelia, along with former Bell Labs director and former Lawrence Berkeley National Lab head Charles Shank. According to Shank, despite their different interests — Schank has a background in chemistry and an interest in optics — he and Brenner are proving that even Senior Fellows enjoy branching out. “I’ve had just an enormous good time talking with Sydney and the way he thinks about biology and technology… I’ve learned a great deal from Sydney already.