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February 2009: Running in Place to Stay Current

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It's a balancing act, to be sure, to get and keep a core lab facility up-to-date with new technologies and services. There are many facets of running a shared resource that need to be considered when a core looks into acquiring or upgrading a tool or changing a service. There's the gamble of whether that new technology will be the one to take off or not — after all, no one wants to invest time and money in someone's Betamax and miss out on VHS.

Not only that, but the mandate of most core lab facilities is to be the best resource they can possibly be for their institution's faculty, to provide the best services that fulfill their users' needs, and to give the best data at the lowest price. "We want that the technology delivers for them and that they are happy. My boss says, 'Your only task and goal is to have satisfied users,'" says Vladimir Benes, who heads up the genomics core facility at EMBL-Heidelberg.

Not all core labs are made the same. Some labs, like Pamela Adams' at the Trudeau Institute, provide a variety of molecular biology services to a small group, and others, like Chris Harrington's at Oregon Health and Sciences University, offer a specialized service — in her case, microarrays — to a larger group of PIs.

Based on their mandate and on users' need, cores also take different approaches to which kinds of technology they bring in. As George Grills, the director of core facilities operations at Cornell University, explains it, there are three levels of technology that people use. First, cutting edge. For that, the core lab needs to have the budget, infrastructure, and staff to implement a technology that isn't yet worn in. "To be at the cutting edge means you need to be able to withstand some bleeding, some pain," he says. The next level, early access, is Grills' "sweet spot." Here, the technology has many of its kinks worked out but isn't yet widely used, giving Grills the chance to optimize the technology for real-world samples and apply it in new ways. The third category is where many core labs fall: the standard user level. They just want something reliable that'll give them the high-quality data they need.

Increasingly, this balance between staying relevant and a good resource for users is being perturbed by a faltering economy. At SUNY Albany, Sridar Chittur, the director of the DNA microarray core, says that his facility had been considering a next-generation sequencing machine, but due to the turmoil on Wall Street, the state of New York is in a hiring freeze — meaning he wouldn't be able to bring in the staff to run the instrument. "The bottom line is when you open your wallet, you actually have to have the money to do it," he says.

Coming down the pike

Part of the act is to squeeze in the time between sample runs to stay on top of what's coming out and predict which of the tools will last. "In core facilities, most of the time, people get inundated with just running day-to-day samples and you become good at what you do, but you don't usually have the time to find out what else is on the horizon. You have to find the time to do that because you need to be more flexible," Chittur says.

Many core managers turn to the literature, vendors, and each other to stay current. EMBL's Benes tries to stay on top of papers. "I think that Nature Biotechnology is, for example, going good; Nature Methods is going good. They occasionally get things which are still in early phases, but have [the] prospect of something cool coming out," he says. After something good catches his eye, he tries to follow up on it. Benes also cultivates his relationships with vendors, noting that this process takes time. "We are more partners in discussing things, so they come earlier to us [when] something new is coming," Benes says.

Networking with other cores can also be helpful. When Katia Sol-Church's biomolecular core lab at Nemours switched from slab gels to electrophoresis, she and her users experienced some growing pains — but she says it would have been worse if she hadn't heard from other core labs. The new data she was getting was noisier than it used to be from the slab gel. She says other core labs told her, "'Don't worry about that, it's not the machine; the machine is perfect, just decrease your dye.'"

Trudeau's Adams adds that experience is needed to be able to gauge which instruments are worth getting, and networking is an important part of gaining that experience. "I think there's a lot of new pieces of equipment that come out every year and what you have to be able to judge is whether it is just a flash in the pan or whether it is going to have some long-term use," she says. "That's sometimes a hard thing to decide, but you do get a feel for it and that's where experience comes in."

Meeting people at conferences is another way to hear about what's coming and what people are using and experiencing. Valerie Scott, the senior director of scientific services at the Jackson Laboratory in Bar Harbor, Maine, makes sure that she and other core leaders there attend at least one meeting per year. "You can accomplish a lot of things. You know who else is out there using what, what their experience has been, and who you can tap into to try in terms of outsourcing [or] collaboration," she says.

Grills finds networking so essential that he founded the Northeast Regional Core Lab Director's meeting (affectionately known as the NERD meeting) for core lab directors to meet and chat, and as a complement to the larger Association of Biomolecular Resource Facilities and Analytical Laboratory Managers Association conferences. It started as Grills having "a bunch of friends over to informally talk and vent and go to the bar and have a few beers" and grew into a formal meeting, but with a networking bent.

"Peer-to-peer learning is worth more than gold. I think that folks that don't take advantage of that through whatever mechanism — professional organizations, technology journals — are being short-sighted," Scott adds.

What users need

Even when core lab directors do know what's the latest, hottest technology, it still might not be a tool that their users need. "If the instrument is standing idle and collecting dust, [no matter] how fancy it is, it simply makes no sense to have it," EMBL's Benes says. To assess just what investigators needs, core lab directors employ a variety of techniques while also educating their users about what technologies are out there.

One way they keep on top of what users need is as simple as chatting with customers. "I have to sort of put my ear to the ground," Adams says. "Sometimes people will request things of me, so I initiate a project sometimes. It is very important to know your user base."

Other times, it takes a little planning to see what users need. This can include offering technical seminar series, setting up surveys, or hearing from a faculty advisory board.

At Cornell, Grills runs a university-wide advanced technology seminar series for which he brings in someone from the vendor's research and development team or an investigator, either from Cornell or outside, who has been using the tool to introduce it and its uses to faculty members. After the talk, Grills follows up with the faculty to have them speak with vendors about the technology, what it could do, and which applications they might use it for. "We really provide a firm foundation, knowing that if we bring them in, they'll actually be used," Grills says.

On a smaller scale, Sol-Church organizes technical seminars as educational sessions for the clinicians, researchers, and staff at Nemours. She says that sometimes she doesn't recognize that a particular researcher would be interested in a technology, especially if the research is taking a new turn. "By educating them and making them aware of what's going on out there, then they can come back to me and say, 'You know what? This is something I can use for my research.' Then we can talk about it and we can together identify that there is going to be a certain group of people that are going to be needing this type of technology," Sol-Church says.

Another way to keep abreast of what users are doing is to attend departmental seminars. "I go to all the seminars that we have," Adams says. "I attend all those things so that I am very familiar with what everybody is doing. If I don't exactly understand every aspect of the science, I at least understand the tools they need to use and then I make proposals to the administration and to the faculty."

There are also formal options to take, such as issuing a call to the community for information, doing a survey, or setting up an advisory board to aid core labs to make their services and technology decisions. Grills uses a number of these approaches. His core center issues RFI-like calls as a way to find out what faculty want, particularly if they'd like a departmental core to be folded into Grills' larger center or a completely new core. The problem there, he says, is to be sure that the resource will truly be university-wide. "You don't want the core to be captured by any particular faculty or small group of faculty or department or school or college if you really want to be a university-wide resource," Grills says.

Each of his core facilities has a faculty advisory board made of three to eight people. The boards give feedback to the cores. "The facilities director provides the report and there's discussion about the scientific direction. We get direct feedback then as to whether or not we're going appropriately," Grills says.

The Jackson Lab has a similar setup, tapping faculty advisors as a source of information about the direction the core should be taking. "Faculty advisors along with the user base and our more advanced manager … really are our source of information about what kind of critical new technologies are evolving," Scott says.

Furthermore, at Jackson, they plan out their capital acquisitions years in advance — even if they are not sure what those acquisitions will be. "We've got a five-year plan of what we think we need and when we think we'll need it," Scott says. "At fiscal year 13, there might be a couple of items up there that are placeholders for emerging technologies. It doesn't mean that those things all [get] funded, but we have a sense of what we think we'll need to spend to replace aging equipment that is essential."

When Yale's Carol Mariani was considering taking a piece of real-time PCR equipment that isn't well-managed or maintained under the wing of her DNA analysis core, she surveyed her users to see if they would use the service if she charged for it. Sometimes, she says, you don't get the response you'd expect: the machine wasn't being used enough to justify her pulling it into the core. "Unfortunately, it's been kind of abandoned," she says.

Paying the price

The next part of the balancing act is that new tools and technologies come with a hefty price tag, both for the instrument itself and to run it effectively. The price of an instrument often isn't just the sticker on the box. For next-gen sequencers, for example, there are the expenses of housing and running the sequencer, reagents and disposables, and bioinformatics and telecommunications infrastructure, not to mention the salary of the staff that performs the experiments.

Many cores first turn to grants from a government funding agency such as NIH or NSF; the next line of requests can go to the state, institution, or investigators themselves. "We'll take money from whoever is willing to give it to us," Albany's Sridar Chittur says with a laugh.

Many cores, though not all, have a fee-for-service structure to help them recover some of costs, yet they are not-for-profit entities. It's tricky. "You don't want to overcharge people, because otherwise they are not going to use your service … and then they may go outside," Nemours' Sol-Church says. "You have to make sure you have institutional support, but also that your core customers realize that this is the real cost of the service that you are getting because sometimes they don't."

"You often need then an alternative source of funding beyond fee-for-services," Grills adds.

Capital expenditures, Chittur says, tend to be easier — at least for him at a state school — since there are state funding agencies that he can ask for money in exchange for the instrument becoming a university-wide or statewide resource. Other cores don't have that option and head to funders like the National Center for Research Resources. "Our first line is to go for government funding," Grills says. "We apply for NIH and NSF shared instrumentation grant funding."

At Nemours, Sol-Church has a COBRE center grant from NCRR that allowed her biomolecular core to upgrade its sequencing services and incorporate real-time PCR into the core's offering. At Yale, Mariani's core was established in 2004 after a group of Yale researchers applied for and received an NSF multiuser equipment grant that allowed them to purchase a capillary sequencer from Applied Biosystems. Last year, they applied for a new NIH grant to upgrade to a faster machine but learned that the application wasn't awarded. Instead, Mariani's core turned to Yale to make its case for the funding. She recalls telling them: "We're breaking even, we're doing really good. It's time to give us something for that rather than just saying, 'You guys are doing great.'" Yale has since found a way to get her core a new machine.

In this funding environment, Grills says, even highly rated grants aren't awarded. In tight situations, he sometimes turns to the faculty for money. "The second line really is to see if there are groups of faculty that would be willing to throw money into the pot from their grant funding or their startup funding, and to also go to departments and schools and colleges to see if, in a collaborative way, we can pull together this funding," he says, adding that the researchers then don't have to worry about the upkeep of the machine.

Buying the tool

When all the other parts fall into place, next comes the act of actually going out and finding the instrument that is the best fit with users' research — without breaking the bank. To get down to the business of buying an instrument, a little research needs to be done first. "I think the difficult thing is buying equipment," Mariani says.

To ease the pain, many core lab managers turn to their network of colleagues, such as ABRF, for guidance. "It gives you a good opportunity to find out which pieces of equipment are the ones that are really going to be useful, and also you can do some negotiating that way," Trudeau's Adams says. "You can find out prices that other people have paid and use that as a bargaining tool."

What's already out in the literature and materials from the company also gives a sense of what to expect from a piece of equipment. When deciding which array platform to buy, OHSU's Harrington and her core first reviewed materials from the companies, then had them visit. "We had companies come and present to us, and we drilled deeply into the pricing structure for arrays and reagents that would be needed to run the platform and compared those against what we already have in-house," she says.

When EMBL decided to acquire a next-gen sequencer in 2007, the core lab team based its decision in part on what projects the tool would be used for. From a survey of group leaders, the core decided that the Genome Analyzer from Illumina would be the best fit. Researchers were interested in immunoprecipitation pull-down experiments for which Benes says short fragments would suffice. Benes says that if more of the faculty had been interested in de novo sequencing, then 454 would have been a better pick than the Solexa or the SOLiD. "A year later, still I see the decision to acquire Solexa a good one — and there is a second instrument coming, and that very likely will be again Illumina/Solexa," Benes says.

After deciding which tool to get, the instrument is then slowly phased into the core lab as the technicians get the hang of how to work and optimize it so it serves as a robust resource. After a training period, Grills' labs have a time of early access and validation use during which a small number of investigators provide samples to test out the technology. When staffers are sure that the tool is robust, access is opened up as a shared research resource.

Another way to get the hang of an instrument is to try it out before buying. "We always ask for demos," says Mariani, adding that when she was in the process of buying a liquid-handling instrument, the company brought in a smaller model that she toured around campus to show researchers.

Benes also uses demos as a way to see if the instrument will be used or sit idle. He identifies faculty that he thinks would be interested in the technology and asks them to pilot the tool. "People are a bit reluctant to acquire or adopt new things, so it's much easier for argument if you have an internal test case and then people can use it as a reference," he says, though he adds that even if the pilot is successful, the instrument still may not be procured.

In the case when there isn't enough of a critical mass, money, or the proper infrastructure to buy an instrument, core labs might still provide that service by drawing on their network of nearby institutes. For example, Benes doesn't have the setup to run Illumina arrays, but a cancer center also located in Heidelberg does, so he sends his researchers there. "It's working both ways — so they know if they need something that they haven't got, they can come here and we can help them out or work with them," Benes says.

At the Trudeau Institute, Adams doesn't provide a microarray service, so she also outsources. "Microarrays require a lot of bioinformatics, and we're small and we don't have a bioinformatics department," she says. She encourages her users to collaborate with other, larger institutions that do have microarray capabilities. Her core is still involved in the process, though. Her team prepares and QCs the RNA before sending it off, and when the data comes back, Adams validates it with real-time PCR. "If I am not able to provide a service, I can find a way to provide it ... through collaborations," Adams says.

It often works out well for both parties; one gets its samples run and the other has its machine running full tilt. "Their instrument gets run 24/7 … so they don't have any downtime, so they benefit from it. And you don't have the expenditure of buying the instrument and maintaining it, but you are still involved in the new technology, so it keeps you on the cutting edge," Albany's Chittur adds.

It's the economy

A new wrinkle core facilities have to keep in mind is the economy — cores are already feeling the pinch. "We're battening down the hatches to ride through the storm of the turbulent economy. That requires very, very strategic planning in terms of making sure that you're really doing efficient spending and doing the most effective type of cost recovery you can," Cornell's Grills says.

At OHSU, Harrington is looking into making some changes to stay solvent. She is considering merging separate cores to integrate resources in order to be more efficient and to move her assays to higher-throughput platforms. "That might slow down data delivery for some projects while we wait for numbers of samples to get to a certain point where we can run it more efficiently, but overall [that] can reduce our costs and our need for labor," Harrington says.

Though Trudeau's Adams is expecting NIH grant money to be a little tighter, she thinks core labs are well positioned to make it through a downturn since they provide essential services to researchers. "I think there's going to be little less money, but I don't think we're going to be losing our jobs like if we were in the automotive industry," she says. "I think the academic sector is relatively stable."

How Researchers Can Take Part

Not working at a core lab? Here are a few things you can do to help your local core stay the course — and make sure your technology needs are known.

Stop by for a chat
Just talking to managers about your research goals helps them understand what you are looking for in a core lab.

Fill out surveys from your core facility
It's a quick and easy way to have your voice heard.

Join an advisory committee
It's a more formal way to affect the direction of a core lab. If you haven't been invited, it doesn't hurt to ask a core lab member how to join.

Attend technology seminars
See what new technologies are on the upswing at these demos — one may be just right for your research.

Ask for help
Even if that core doesn't offer the service you are looking for, it may still be able to help you get the work done in-house or by finding another service provider.

Pitch in
If you need a big-ticket instrument and your core facility hasn't been able to get funding for it, work your connections at your institution. You may be able to pitch in a portion of your startup package, an existing grant, or some other funding source and pool that with funding from other researchers to help the core lab acquire the tools you need.

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