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Shared Quality

Facilities ensure multiple users access to equipment of the latest generation, and the practice gains adherents in São Paulo State

The services of confocal microscopy and gene sequencing are among the most requested of facilities in São Paulo

EDUARDO CESARThe services of confocal microscopy and gene sequencing are among the most requested of facilities in São Paulo EDUARDO CESAR

In August 2013, the University of São Paulo (USP) inaugurated a laboratory that brings together, in a single environment, a number of items of modern equipment for shared use by researchers in cellular biology and genomics, along the lines of the research facilities found at universities in other countries. Distributed among 10 rooms of one of the buildings at the USP Institute of Biomedical Sciences Center for Research Support Facilities (Cefap-USP), the lab complex makes available to researchers from all over Brazil the latest-generation sequencing services, microscopy for studying living cells, cell separation, mass spectrometry for identifying macromolecules, and other services. In the year since it opened, the facility has already welcomed about 80 research groups and assisted with studies on subjects such as DNA repair genes, the search for drugs to combat malaria and skeletal muscle plasticity, among many others. Most users came from USP, the Federal University of São Paulo (Unifesp), São Paulo State University (Unesp), and the University of Campinas (Unicamp). Cefap received an investment of about $4 million from FAPESP for equipment purchases, while the structure of the laboratory and the hiring of staff was financed by USP. Additional help with the purchase of equipment came from USP itself, and from the Brazilian Federal Agency for the Support and Evaluation of Graduate Education (Capes).

In order to use one of the 15 pieces of equipment at the laboratory, researchers need to go to the Cefap website to check availability and schedule a date and time for using it. One of the most popular services is confocal microscopy, used by 51 research groups for more than 180 projects. It is an important tool for cellular biology studies, since it helps locate proteins inside cells and visualize the interaction among those proteins. Two pieces of equipment are available for this service: a Zeiss LSM 780-NLO microscope, which uses a laser to generate images of fluorescence in cells, and the InCell Analyzer 2200 GE, suitable for research projects that need a large number of images. “The idea behind the multiuser equipment concept is to facilitate access to the most advanced equipment, which is difficult to purchase,” says Carlos Menck, a professor at ICB-USP and president of Cefap.

A researcher from the IQSC-USP places samples in the mass spectrometer for analysis

EDUARDO CESARA researcher from the IQSC-USP places samples in the mass spectrometer for analysisEDUARDO CESAR

Examples such as the one at Cefap are occurring more frequently. In São Paulo State, approximately 50 such facilities have been established since 2009, following the publication of the second call for proposals under the Multiuser Equipment Program (EMU), established in 2005 by FAPESP. The program has now awarded about R$250 million for the purchase of shared use equipment. In 2009, investments of about R$167 million were approved for purchase of 250 pieces of equipment, more than 200 of which were valued at over $50,000 apiece.

The research facilities model ensures wider access to technologies that are vital to anyone who conducts studies at an international level. It is also more economical, because methods and inputs are shared. In Europe and the United States this kind of arrangement is part of the routine for many research groups. In Brazil, experiences of this kind were found only in the isolated situations that inspired the most recent initiatives. The principal example is that of the Brazilian Synchrotron Light Laboratory (LNLS), in operation since 1997. It houses the only synchrotron light source in Latin America, used by Brazilian and foreign researchers in studying the structures of proteins and materials. “The Multiuser Equipment Program is gradually succeeding in encouraging the ‘facilities culture’ in this state,” observes José Antonio Brum, a professor at the Gleb Wataghin Physics Institute at Unicamp and assistant coordinator of Special Programs at FAPESP.

Mass spectrometry with an electrospray ionization source at Cefap-USP

EDUARDO CESARMass spectrometry with an electrospray ionization source at Cefap-USPEDUARDO CESAR

In June, Brum participated in the first Workshop on Multiuser Equipment and Facilities, attended by representatives of facilities established in São Paulo. According to Brum, many researchers are still reluctant to use equipment set up in laboratories that are administered by other groups. “Many would like to have their own equipment,” he says. FAPESP encourages the use of such facilities by researchers in projects that it finances, unless the investigator can demonstrate that acquisition of a new item of equipment is absolutely essential.

Some figures provided by the National Nanotechnology Laboratory (LNNano)—which, like the Synchrotron Laboratory, is affiliated with the Brazilian Center for Research in Energy and Materials (CNPEM), in Campinas—suggested that resistance to shared use is diminishing. “The demand for our equipment and consulting services increases every year,” says Fernando Galembeck, a professor who retired from the Unicamp Institute of Chemistry and is now director of LNNano. At its five laboratories—Electronic Microscopy (LME), Microfabrication (LMF), Metals Description and Processing (CPM), Surface Science (LCS) and Nanostructured Metals (LMN)—about 2,700 research projects had been executed as of 2013. The LME, the oldest of LNNano’s laboratories, has itself already assisted with more than 2,000 projects. In 2001, 86 projects had been submitted to the LME. By 2012 the figure had jumped to 207. The number has not increased in the past three years because almost all the lab’s installed capacity has been committed. Founded in 1999, the LME has been part of LNNano since 2011.

A Cryo Electron Microscope at LNNano permits obtaining structures at nearly atomic resolution

EDUARDO CESARA Cryo Electron Microscope at LNNano permits obtaining structures at nearly atomic resolutionEDUARDO CESAR

According to Galembeck, shared facilities perform an important role in the science and technology system, which is to accelerate the progress of research efforts. The LNNano installations are increasingly being used by researchers who are not on the institution’s staff. At the LCS, they accounted for 50% in 2012; 70% in 2013, and almost 80% as of May 2014. Most of the outside users came from Unicamp (13%), Unesp (10%), and USP (9%). The highest demand is for electronic and probe microscopy services, which are used to describe substances and develop new materials in academic and business-related projects. Analysis of polymer structure, one of the final stages of the doctoral studies being pursued by Rafael Bergamo Trinca at the Unicamp Institute of Chemistry, for example, could not have been completed without the aid of a Nanoscope III, an atomic force microscope that provides three-dimensional images of the surface of materials on a nanometric scale. Trinca’s advisor, Professor Maria Isabel Felisberti, suggested he contact LNNano, which not only has the equipment but also offers training in its use. “I learned to use the microscope and how to get the best results out of it,” Trinca says. His research, supported by FAPESP, seeks to obtain biocompatible membranes that could, for example, release drugs when stimulated in a certain way, such as by increasing the temperature.

Training for the so-called super-users, i.e., researchers who will have become totally familiar with the equipment they need and can use it without the help of technical personnel is something that the USP’s Cefap is also trying to develop. “We have a limited number of experts working in the laboratories. One solution is to train the users,” Menck explains. But most of the work at the center is still done by the technical personnel, working with samples sent them by researchers. “Consolidation of a “research facilities culture” is proceeding slowly in Brazil because, among other factors, there is still a shortage of technicians who can operate the equipment,” Menck observes. “Furthermore, many facilities coordinators cannot spend all their time managing the laboratories because they are also directing research and advising students.”

A technician at LCE-UFSCar evaluates images of carbon nanotubes generated by a scanning electron microscope

EDUARDO CESARA technician at LCE-UFSCar evaluates images of carbon nanotubes generated by a scanning electron microscopeEDUARDO CESAR

To remedy this situation, the Central Laboratory for High-Performance Technologies (LaCTAD), at Unicamp—a shared facility promoted by FAPESP and inaugurated in 2013—instituted the position of general manager, someone dedicated full time to administering the laboratory. The post is currently held by chemist Sandra Krauchenco. “The laboratory needs to be professionally managed,” says Paulo Arruda, a professor at the Institute of Biology at Unicamp and a member of the managerial council of LaCTAD, a laboratory established to support research in genomics, bioinformatics, proteomics, and cellular biology. FAPESP invested R$6 million in equipment purchases for this laboratory, under the EMU Program.

For its work in genomics, LaCTAD has three sequencers. In the field of proteomics, one apparatus performs liquid chromatography in order to analyze and purify proteins. There is also a calorimeter, used to determine the thermodynamic parameters of biochemical interactions (see Pesquisa FAPESP Issue No. 206). In cellular biology, the most requested service is that of confocal microscopy which, in contrast to other equipment, requires the user to be present at the moment of analysis. “In the case of microscopy, the user is the one who looks at the image and decides which part of the cell will be observed,” Krauchenco explains.

Personnel at LaCTAD, at Unicamp, observe intestinal flora cells, using a confocal microscope

EDUARDO CESARPersonnel at LaCTAD, at Unicamp, observe intestinal flora cells, using a confocal microscope EDUARDO CESAR

One feature that makes LaCTAD unique in relation to other laboratories is the assistance given the researchers in all phases of their project, from planning and preparation of samples, to processing and analysis of the data obtained. In other countries, if users do not know how to properly ask for what they want to extract from a sample, the experiment may go wrong, because the facility does precisely what a researcher asks be done. “Here, we contact the researcher and think about it together,” Arruda says.

Before LaCTAD was established, members of the council visited laboratories in the United States to learn more about the model adopted by institutions in that country. One of those facilities was the DNA and RNA sequencing facility at the University of North Carolina (UNC) at Chapel Hill, coordinated by Piotr Mieczkowski. One of the missions of the UNC facility is to encourage research that develops methods that can be implemented in its services. That feature attracted the attention of LaCTAD. “We want to invest in that kind of research talent, in order to improve the use of certain methods and create others,” Arruda notes. In a lecture given in São Paulo, Mieczkowski emphasized the “industrial” pace at which the UNC laboratory operates: in 2013, it performed 6,000 sequencings. “The development of a multi-user facility must be associated with large, stable research projects,” Mieczkowski concluded.

Another facility that is prominent in the U.S. is found at the Duke University School of Medicine. It has more than 70 multi-user laboratories located at different places around the campus. Each has its own website by which the user can request a service and see what fees will be charged. The USP School of Medicine also follows a decentralized model in which equipment is available at different locations. But coordination is handled by the Premium Network of Multi-User Equipment, which arranges for access to biomedical research technologies by researchers from USP and those from elsewhere. One of the most requested services is confocal microscopy, using equipment, the LSM 510 Meta from Carl Zeiss, that was purchased with financing from FAPESP.

In some cases, a shared facility may serve as a meeting point for arranging scientific partnerships. At USP’s Institute of Chemistry of São Carlos (IQSC), a high-resolution mass spectrometer was pivotal in helping two research groups become acquainted with each other. The equipment had been purchased in 2013, with funds from FAPESP, for the group headed by Emanuel Carrilho, an IQSC professor who is studying biomarkers to be used in diagnosing cancer and diseases like malaria. Two professors from the Riberão Preto School of Medicine (USP), Vitor Marcel Faça and José César Rosa, who are also working on proteomic research related to cancer, asked for permission to use the equipment, since they were not on the original team of users who had submitted the project to FAPESP. What at first was simply the provision of a service became a collaboration. “We realized that we had objectives in common,” Carrilho says. The spectrometer, a Velos LTQ Orbitrap, cost $700,000 and is coupled to a high-performance liquid chromatograph used to isolate proteins.

This equipment was important for a research project coordinated by Daniel Rodrigues Cardoso, of the IQSC-USP, in partnership with the Brazilian Agricultural Research Corporation (Embrapa) and the University of Copenhagen, in Denmark. By adding yerba mate to cattle feed, researchers achieved a more tender red meat that is less perishable. The effect is attributed to the presence of antioxidants in the mate. The spectrometer is being used to understand the changes in the animals’ metabolism. “We are analyzing samples of meat and mate in order to identify the metabolic changes,” Cardoso says.

The Structural Characterization Laboratory (LCE) at the Federal University of São Carlos (UFSCar) is actively training microscope technicians in order to optimize the use of its equipment, as well as to provide services. “Our model is based on the training of microscope technicians because we cannot make such personnel available for eight hours a day to operate each of our eight electronic and probe microscopes,” explains Walter Botta Filho, coordinator of the LCE. “We want our regular users to depend as little as possible on help to operate the equipment, which makes scheduling its use more flexible,” he says. The concept of “multiuser facilities” is nothing new to the Department of Materials Engineering, which houses the LCE. Since 1976, the microscopy and X-ray laboratory of the unit have been open to researchers from other institutions. This circumstance laid the foundation for the LCE, 10 years later, to systematize the model for other services. Between 2012 and May 2014, 1,018 researchers used the facility; 419 of them were qualified to operate equipment by themselves. Botta notes that when researchers need to schedule the use of a piece of equipment, they may decide either to operate it themselves, after completing the training, or to ask for help from a technician. At any rate, they are charged for the time they use the equipment.

José Antonio Brum believes that ultimately, several models of facilities will coexist in São Paulo. “Every laboratory has its own problems and demands, which results in a variety of models. That is not necessarily a bad thing,” he says. Another challenge is learning how to manage resources. According to Brum, many laboratories are unable to accurately estimate the costs of labor and the maintenance and depreciation of the equipment, which makes it hard for them to set the fees to be charged for the services. The workshop sponsored by FAPESP discussed the circumstances in which facilities should charge for use of their equipment. “Ideally, they should always charge,” argues Menck, of Cefap. “It’s a way to build respect for the service. The problem is that Brazilian research culture is not going in that direction,” he adds. At Cefap, the fee for use of the confocal microscope for a period of four hours is R$200 for projects sponsored by government agencies and R$275 for those sponsored by other sources. Menck says that in general, its fees were primarily determined by taking into account the expense of inputs. The funds obtained from user fees are not sufficient to pay for the contracts to maintain some of the machines, which can cost R$150,000 each, per year. “If we were to include other expenses, the fees we would have to charge would not be competitive,” Menck says.

The situation is different at LNNano, where researchers are not charged for the services. The laboratory is affiliated with the Ministry of Science, Technology, and Innovation, which transfers funds every year to cover equipment maintenance, salaries, and inputs. “We only charge the companies, which contact us in connection with research and development projects and for services,” Fernando Galembeck says. The fees charged by the facilities are not always competitive. “When Brazilian researchers have collaborators in another country, they can pay the fee charged to internal uses at the facilities operated by their partner universities, which are usually lower than the fees here,” explains Sandra Krauchenco, of LaCTAD. “When a user does not have any international collaboration, then we can compete on an equal footing,” she says.