Bond LSC collaborations lead to intellectual brainstorming and technology sharing

Taken together, these five stories show how the operating philosophy and the building design at the Bond Life Sciences Center has led its researchers to share technology, expertise, and ideas, which in turn is yielding fruitful collaborations and scientific innovations.

Extraordinary cooperation wins D Cornelison a perfect grant score

Cornelison

D Cornelison needed help, quickly. Her application for a grant from the National Institutes of Health (NIH) to study satellite cells, which are stem cells in muscles, had just been returned with high marks, but not quite high enough for funding.

Reviewers with the funding agency made comments suggesting Cornelison’s proposal would stand a very good chance of being funded upon resubmission if she could demonstrate certain technical abilities and answer some specific scientific questions.

This news arrived 10 days before a resubmission deadline, and getting the data to respond to the reviewers’ requests would involve conducting several types of tests that Cornelison’s lab is not currently equipped to perform. That’s why she needed immediate assistance.

Bond Life Sciences Center colleagues came to Cornelison’s aid without a hint of hesitation.

Bruno Marchand, then a post-doc in the lab of virologist Stefan Sarafianos, spent several days with Cornelison lab member Josh Thompson figuring out the best way to turn a complicated sample into a group of simpler ones. They used specialized equipment in Sarafianos’ lab to separate a sample containing hundreds of different proteins into what they expected would be thirty or so less complicated fractions. Unfortunately, after being separated this way the proteins were so diluted in each sample that the usual means of visualizing them in a gel wouldn't give any results. Cornelison knew there was a better way, using a silver-stained gel, but she had never tried it before.

“I thought of Scott Peck,” Cornelison said. He studies plants and the bacterial pathogens that infect them. “I called him on a Sunday morning because that was when we finally got the samples in.” Peck came in that afternoon with a box full of chemicals and they did the analysis that day.

The results clearly showed the proteins in the original sample had been separated neatly by size in the fractions made in the Sarafianos lab. Thus, one of the reviewers' concerns had been put to rest.

Sarafianos

Peck

Thelen

To follow up on the grant reviewers’ other request, Cornelison's graduate student Ashley Seigel used special antibodies to remove what they thought were the active components of the mixture, then tested it against the whole sample. But she needed to prove she had actually removed what she had intended to, which would require analyzing the sample in a mass spectrometer. Nagib Ashan, a postdoctoral fellow in Jay Thelen's lab, graciously analyzed Cornelison’s sample alongside his own on their mass spectrometer, and was able to provide the confirmation they needed.

“Really, without Bruno’s help, and Scott’s help, and Jay’s and Nagib’s help, there is absolutely no conceivable way we could have turned this grant around in time to resubmit it,” Cornelison said. “We did resubmit it, and it came back with a perfect score,” which positioned her grant as a top priority for NIH funding. It later passed all subsequent tests and was funded.

“This was entirely LSC karma, just knowing that I could just go ask Bruno, or Stefan, or Jay, or Scott, and the instant answer is ‘yes, of course, we’d be happy to help.’ Not ‘I’m too busy’ and not ‘sorry, I can’t,’ and not ‘what are you going to do for me if I do this for you?’ That’s one of the reasons I love being in the Life Sciences Center. Everyone pulls together, all the time,” Cornelison said.

Building designed to encourage cooperation

Hearing about the group effort on Cornelison’s behalf “made my day” said Bond Life Sciences Center director Jack Schultz. “There couldn’t be a better example of the value of being in this building,” he said.

Cornelison’s dramatic experience reflects a mode of operation that is normally more low-key, but functions regularly within the Bond Life Sciences Center; that mode fosters intellectual brainstorming and technology sharing. The center, completed in 2004, was conceived as a cauldron suitable for brewing a veritable stew of science, hopefully with unlimited recipes for cooperation and collaboration.

“The design of the building makes it so easy, in fact, imperative to interact with other people. It plays a tangible role,” Schultz said. Labs share common lounges. A central atrium and an open five-story staircase provide natural meeting places for busy people to mingle on their way to and from their labs and offices.

Bumping into people on the stairs “seems to lead to a lot of conversations that might not happen otherwise,” Schultz said. Plenty of comfortable seating nearby offers convenient spots to complete such conversations. “I think the building is an active player” in promoting cooperation between labs, he said.

The mix of occupants also contributes to the stew. As a diverse research center devoted to all life sciences, numerous departments are represented at the LSC; however, no department is specifically home-based in the building.

“Plant sciences faculty rub shoulders with biochemists,” Schultz said, “and a vet pathobiology researcher might discover common interests with a biological engineer.”

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Liscum and Hannink collaborate to identify parallel systems on a cellular level

This concept is working for investigators Mannie Liscum and Mark Hannink. At first glance, their fields couldn’t seem further apart. Liscum conducts research on the responses of plants to light, or phototropism. Hannink investigates in mammals the response of cells to oxidative stress, a condition implicated in kidney, liver, and neurodegenerative diseases, among others.

Liscum

Hannink

Yet these two scientists – one studying plants and the other mammals – conducted a cooperative investigation that spanned over a year. They found common ground at a very basic cellular level.

Hannink’s lab is equipped for and is experienced in studying the “proteasome” and its associated proteins in mammals. The proteasome acts as a cellular “garbage can;” it functions to destroy unneeded proteins. All plants, animals or other organisms at times have a need to dispose of outdated or unwanted cells or proteins, and the mechanism to do this, the proteasome, is consistent among life forms on Earth.

Liscum had noticed similarities between a certain plant protein that he studies and an animal protein that Hannink studies. He wondered whether his plant protein NPH3 functioned within the proteasome system in the same manner as does the animal protein Keap1; in particular, he sought to learn whether it interacts with a third protein found in both plants and animals, known as Cullin 3.

Hannink’s expertise and equipment helped Liscum conduct research to address this question. Bingo. Both the plant and animal proteins in question relate to Cullin 3 in much the same manner.

“It was huge, showing that our protein did truly interact (with Cullin 3),” said Liscum. “That work was done in a mammalian cell system first; we verified it in a plant cell system, but it was much easier to do initially in the animal cell system.”

“It (NPH3) certainly wouldn’t be doing the same things in plants (as Keap1 does in animals), (because) the biology is completely different,” Liscum said, “but on a biochemical level, it’s doing the same thing.”

The findings were published October 2011 in Plant Cell, the top journal in plant biology.

About the collaboration with Hannink, Liscum said it probably would not have happened “had we not been physically in the same building, and almost certainly would not have happened had I been clustered with people who do the exact same things I do, because we would think the same.” But in groups of mixed scientists, “you have these epiphanies and you change the way you do things.” He thinks interesting things happen by “being with lots of really diverse, creative people.”

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Gassmann, Garcia team up to explore immune systems’ ability to recognize “self”

Similarly, common ground and a collaborated project arose between Walter Gassmann, who studies plant immune systems, and Michael Garcia, who studies the development of the mammalian nervous system.

Gassmann

Garcia

As in the aforementioned collaboration, these two scientists are studying two similar proteins, one found in plants and one in animals. Gassmann has recently discovered the function of SRFR1, (suppressor of rps4-RLD, - aka “surfer-one”), the plant protein in question. As part of the plant immune system, this protein helps a plant to identify compounds as “self” and “non-self.”

The collaboration emerged after Garcia read about Gassmann’s work while serving on an internal grant review panel. “It was truly a struggle to read his grant, not because Walter doesn’t write clearly, but because we all have our own jargon. … I didn’t even know plants had an immune system,” Garcia recalls. But concepts clicked when he read a certain paragraph. “I said, ‘this sounds a lot like major histocompatibility.’ Wow. Who knew plants had (the equivalent of) major histocompatibility? That’s the system in our bodies, a kind of screening mechanism, where we identify what really belongs in our bodies, self versus non-self. This is why organ transplants fail in humans, because we reject things that shouldn’t be inside us.”

The two investigators decided to investigate TTC13 (tetratricopeptide repeat domain 13), a rarely-studied mammalian protein that has much in common biochemically with Gassmann’s well-studied protein, SRFR1.

A compare-and-contrast analysis between these two related proteins is now underway, looking at the question: “is there an evolutionarily conserved mechanism by which plants and mammals use some of the same proteins to do some of the same things with their immune systems?” Garcia said. Much of the work is being conducted by graduate student Stephen Shannon from Garcia’s lab, but utilizes technology and expertise not only from Gassmann’s lab, but also from the Hannink and Liscum labs as well.

While plant and animal immune systems have parallels, they are in no way equivalent. So the two proteins may or may not have common functions. “I think we would all love for this protein (TTC13) to be involved in some part of the immune system,” Garcia said, but the research process is not far enough along to make that determination. “Right now it’s merely a protein.”

Gassmann says even if TTC13 isn’t found to be part of the immune system, “that doesn’t make it uninteresting.” It’s entirely possible that the protein could be “doing the same thing,” in plants and animals, “but in two different physiological processes,” which he would find equally interesting. “Evolution takes something, and swaps parts out, so it does something else. If it works, it works, right? If it doesn’t work, it doesn’t survive.”

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Creative insight leads to technology sharing between Waters and Gassmann

Waters

One element of successful collaborations involving the abovementioned investigators – Cornelison, Peck, Liscum, Hannink, Gassmann, and Garcia – is the ability to either offer or take advantage of the vast repository of scientific equipment in the Bond Life Sciences Center.

A flash of insight led to one technology-related collaboration. Walter Gassmann was in a seminar audience while Sam Waters described how he would be using “chromatin immuno precipitation-sequencing”(ChIP-Seq) technology to unravel certain genetic questions. Waters studies how neurological factors affect the development of motor functions.

Gassmann had a similar need to unravel his own genetic questions about plants. “I realized ‘here’s the guy who can help me answer my question.’ So now we have a research board grant funded to do just that together,” he said. The ChIP-Seq tool “doesn’t care whether it’s (testing) a plant nucleus or mouse nucleus.”

The trick to collaborative inspirations is “a deeper understanding of what’s going on in the building,” Gassmann said. “Just knowing that Sam studies mouse development wouldn’t have triggered that. But hearing him talk about his work, realizing that that’s the technology I want to use, that made it click.”

Hand-in-hand with the equipment itself is the knowledge of how to run it. Gassmann is grateful that “Sam will be there to guide us.” Even though experiment procedures are written up in scientific papers, he said, “it’s very condensed. You don’t have enough space in a journal to really explain step-by-step (for example) ‘here, at this step, you have to be really careful not to keep it on ice too long.’” The ChIP-Seq process is “nothing I’ve ever done before, so it will be very helpful to collaborate with an expert,” he said.

Waters added, “These types of interactions allow all of us to grow.”

Their teamwork goes beyond technology-sharing, Gassmann said. “Sam and I have a lot of intellectual exchange.”

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Data blitz sparked collaboration between Gary Stacey and Heather Hunt

Occasionally, Bond LSC Director Jack Shultz throws a special kind of party that encourages exactly the kind of exchange that led to Waters teaching Gassmann about the ChIP-Seq process. During a “data blitz,” he said, “graduate students, post docs, or principal investigators have five minutes to tell everybody about the most exciting thing they’re doing in their research at the moment. It’s fun.”

Stacey

Hunt

Data blitzes help fulfill Gassmann’s goal of maintaining “a deeper understanding” of the fast-developing fields within the building, and in particular they help expose LSC researchers to the opportunities offered by new investigators.

A new match was born from a data blitz after plant scientist Gary Stacey heard a talk from a new investigator, chemical engineer Heather Hunt, who last year joined the Bond Center community. She hails from the California Institute of Technology in Pasadena and specializes in biophotonics, or the intersection of light and biology.

As a result, Stacey and Hunt are now working on a project using light to measure interactions between a protein and a chitin, to determine how the two bind together, and how tightly. Chitin is the main component in the exoskeletons of insects. “According to Heather, this has never been done before,” Stacey said. “If what we’re trying to do actually works, it would be super cool.”

The collaboration, Stacey said, “is a nice example of where you’ve got a biology lab working with an engineering lab. It’s something that’s very difficult to do if you don’t have the Bond Life Science Center to manage it, because you have to be able to rub up against these people.”

Collaborations are necessary, Stacey said, “because science has become so specialized that you can’t be an expert on everything. But quite frankly the major reason I do it is just because it’s more fun. ... You talk to people, you interact; it just makes it more enjoyable.” Stacey has also collaborated with Gary Weismann, Jay Thelen, and David Mendoza-Cózatl, as well as Peck, Gassmann and Schultz.

Hunt enthused about potential for sharing biosensor technology and innovative ideas

Not everyone can attend the data blitzes, and Hunt says she is eager to get the word out even further about the technology she can share and her willingness to collaborate.

Hunt has built an “on-chip optical biosensor platform.” It utilizes optical fibers the size of human hairs, lasers, and micro-scale optical devices to peer into water or other substances, looking for specific compounds. Using her materials engineering background, Hunt can modify this biosensor to search for a wide variety of tiny particles. She is now focusing on detecting specific pathogens and chemical pollutants within wastewater samples, such as viruses, bacteria, proteins, and even nanoparticles. The biosensor’s range is so sensitive that it can detect these compounds potentially down to the single molecule level, she said.

In addition to working with Stacey, Hunt is currently collaborating with biological engineer John Viator on another in-house project. But she sees opportunities for more partnerships among Bond Center investigators. She hopes her colleagues will put her biosensor to work. “I’m an engineer. I need problems to solve,” said Hunt. “They (Bond LSC scientists) all have different questions that they need answered. Maybe my platform could help answer those questions,” she said.

Hunt’s philosophical outlook about interdisciplinary collaboration goes way beyond sharing technology; it’s the exchange of concepts that excites her.

The most important “cutting edge” of science, Hunt believes, is “the interdisciplinary edge, the overlap between one science and another – between physics and biology, between physics and chemistry, and between engineering and all of the sciences. That’s where most of the exciting innovations come about.”

Being at the Bond LSC allows for interactions among people “with different perspectives,” who “may approach problems in different ways,” said Hunt. “We all talk in different languages scientifically … and when you get people like that together … it’s like translating everything and out of that grows an idea, one that ‘we’ve never thought of doing this way.’ … It’s not just a melding of skill sets … it’s the ideas that come together, that mesh in ways that you wouldn’t necessarily expect.”

Hunt, acknowledging that people conducting research elsewhere sometimes feel isolated, said she thinks scientists working in the LSC “can’t be scientifically lonely because there are so many people around you who are doing such interesting science.”

“In the halls, in the corridors, outside my door … I hear all these things (people talking) and it’s just science, science, science,” Hunt said. “The atmosphere is so conducive to learning and to picking up new things — the science sneaks up on you.” This includes concepts from disciplines unrelated to hers. “There’s this osmotic effect; you start learning things that you wouldn’t before,” she said.

Concerning her collaborations with Viator and Stacey, Hunt said “I’m learning from them and they’re learning from me, and we’re hopefully producing really, really good science. We’re producing things that no one has ever tried before, that nobody’s ever thought of before, simply because we’re here.”

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