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High-Throughput Biology in the Hoosier State

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In between the corn and rust belts, a robust biomedical sector has grown up in Indiana. Purdue University’s Discovery Park, home of the Bindley Bioscience Center, is already on its way to becoming the fulcrum that balances the academic and commercial leanings of the region. Eventually, it hopes to be a member of the most elite systems biology research institutes.

An arm of Purdue University, Discovery Park was constructed to be a model for multidisciplinary scientific research, to promote scientists of different backgrounds working side by side and collaborating on projects that couldn’t be done in separate labs. The park is home to four buildings, with a fifth yet to be constructed, that span centers for nanotechnology and bioscience, among others. Within the 40-acre Discovery Park complex is the Bindley Bioscience Center, an 18,000-square-foot home base to research that goes from genomics to proteomics to metabolomics. Bindley is pursuing projects that float under five umbrellas of signature research: diet and disease prevention, drug discovery/delivery, health and disease biomarkers, nano-medicine, and tissue and cellular systems. Core facilities include those for proteomics, metabolomics, genomics, ionomics, and cytometry and cellular imaging.

“Although this was sort of lurking in the back of folks’ mind, it wasn’t specifically intended to focus on systems biology,” says Director of Operations Charles Buck. “The idea here is to promote multidisciplinary approaches to life science research.”

Lab spaces aren’t owned by any particular faculty member; researchers who have been recruited from various departments across campus engage with about a dozen-member Bindley scientific staff to launch projects within the center. Researchers are encouraged to be entrepreneurial both in seeking out Bindley’s resources and in applying jointly for grants. The administrative staff, Buck says, makes it as easy as possible for investigators to focus on the science rather than proposal management.

According to Fred Regnier, one of the faculty executive leaders and a professor of analytical chemistry, creating Discovery Park and Bindley was a way to encourage an entrepreneurialism that is more common to commercial environments. “Our president said, ‘Could we have entrepreneurship within the university? And if any of you want to put a team of people together and create a center, we’ll give you space to do that.’”

Buck notes, “It’s very collaborative, but I think that’s becoming a feature of academic research because that’s really the only way to get funding now.”

Proteomics and Metabolomics in Cancer

Some of the main projects that Bindley has dug into since it opened in October 2005 are a DOE-funded project to optimize ethanol production with a particular strain of yeast, an NCI-based cancer biomarker discovery program, and a program to upgrade and create new instrumentation, especially in the areas of mass spectrometry and flow cytometry.

“Where we are beginning to define a niche in the systems biology world is in what we’re calling measurement sciences,” Buck says. “We’re coming at it from an engineering perspective and trying to focus on increasing the precision of our measurement in biological systems, in order to increase the richness of the data and make the modeling that’s done on that data more valuable and more likely to lead to advances without large numbers of reiteration.”

Fred Regnier’s lab at Bindley is part of NCI’s consortium for clinical proteomics technologies for cancer, which also includes the Broad Institute, Memorial Sloan-Kettering, Vanderbilt University and the University of California, San Francisco. The consortium is using “very high-throughput proteomics for validation of cancer biomarkers,” Regnier says.

“[Systems biology] involves the simultaneous analysis of a single sample by genomics, proteomics, and metabolomics,” Regnier says. “One of things that the Bindley does is to try to get all those things going simultaneously.” It’s taken some effort to ramp up the proteomics and metabolomics platforms, and he believes that metabolomics has now outpaced proteomics. “Our metabo-lomics capability now, with GC/GC/MS and LC/MS/MS — we’re not unique, I mean other people are able to do this, too — we can probably see in the range of 1,500 to 2,000 metabolites in 30 minutes or so, and in an automated fashion look at 100 samples, and then do various kinds of pattern recognition to the data afterwards,” he says.

Imaging and Analysis

J. Paul Robinson, faculty executive leader and professor of biomedical engineering and immunopharmacology, is taking advantage of collaborations with other scientists to create new imaging technologies. With 30 years of experience in cell analysis, Robinson and his team have been working on advances to microscopy, which he believes needs significant improvement in order to deal with the high-content screening and high-throughput analyses of today’s investigations.

“We’re taking classification routines that are used in other fields … and we’re applying those to what we will call the proximal sensing field,” Robinson says. “You bring those [remote sensing] tools into the imaging world, the microscopic world, the cell analysis world, and before you know it, you’ve started creating completely new applications.”

Another project with which Robinson is heavily involved is an effort to manufacture low-cost, simplified flow cytometers to test CD4 counts in AIDS patients in Nigeria. Discovery Park’s Regenstrief Center for Healthcare Engineering has partnered with Bindley on what’s been called the Cytometry for Life program.

One area that’s required lots of attention here is analyzing data — in particular, finding ways to improve the handling and management of increasing amounts of data. “The argument there is that you’ve got all this information about cells, because we have developed technologies that let you to see and identify vast number of parameters and information about cells,” Robinson says. “However, we haven’t really worked out how to analyze that.”

Buck says that from the scientific perspective, bioinformatics is the biggest challenge right now for both Bindley and progress of large-scale biology in general. “I think that most of the folks that are working in this space would agree that the data handling, management, and mining systems are the most important bottleneck right now,” he says. “We have a major effort underway to develop and implement our data analysis pipeline that will handle diverse data sets, efficiently store and back up data, and then enable investigators to easily enter the data into various analysis packages.”

In the end, it’s the collaborative environment of the center that frees up scientists to explore territory beyond their departmental boundaries. “When you have collaborators like Fred Regnier and all the other people that are here, you have a lot of options of going down pathways that you may not have been able to go down before,” Robinson says.

Name: Bindley Bioscience Center
Host: Discovery Park at Purdue University
Leadership: Mark Hermodson, Professor of Biochemistry, interim co-director
Established: October 2005
Staff: 12 scientific staff members, four administrative staff members, 107 researchers from groups of about 20 faculty members
Funding: Initial funding came from two grants from the Lilly Endowment;
of the total $51 million awarded to Purdue for Discovery Park, about
$7 million went to Bindley. Since then, most of about $30 million in
funding has come from federal agencies including NIH, National Science Foundation, US Department of Energy, and US Department of Defense.
Key research areas: Health and disease biomarkers, drug discovery/delivery, diet and disease prevention, nanomedicine, and tissue and cellular systems
Core facilities: Proteomics, metabolomics, genomics, ionomics, and cytometry and cellular imaging

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