Sitting alone in an office built for two, Joeriggo Reyes may not appear at first to be part of a multidisciplinary team tackling one of the world’s deadliest diseases. The lab gowns or sequencing machines that one typically associates with biological scholarship are nowhere in sight. From his room at UP Diliman’s Institute of Mathematics, however, this biologist and informatics expert finds himself at the crossroads of contemporary cancer research.
As the lead builder of the scientific database for a CHED-Philippine California Advanced Research Institute (PCARI)-funded project, Reyes’ office is the convergence point for data produced by four groups from the Philippines and the US. Once done, it will house information from laboratories in UP Los Ba?os, the University of California Davis, UP Diliman, and the Lung Center of the Philippines.
These researchers—united more by a common vision and fiber optic cables than physical proximity—are using their expertise in systems biology, medicine and chemistry to unlock the secrets of lung cancer, a disease that claims ten Filipinos per hour, according to the World Health Organization.
While building a freely accessible storehouse for researchers sounds like the least glamorous part of the job, Reyes finds his role perhaps the most reflective of how 21st-century science can be done.
Scientists today are increasingly relying on large data sets to bring together previously isolated subjects, and to model the interacting components that make up complex phenomena like cancer.
At the heart of these efforts is the database—where researchers can access massive amounts of data uploaded by their peers and predecessors to solve previously intractable problems. Reyes hopes the repository he is building will not only benefit his fellow project proponents, but other scientists working towards the next generation of breakthroughs in Philippine biomedical research.
What is a database?
While a project that marries biology and information technology can sound daunting, describing a database in itself is fairly straightforward. “A simple example of a database is a Microsoft Excel file,” says Reyes. “In an Excel file, you have rows and you have columns. And in these you have attributes like people’s names and birthdays. That’s a simple database, and we just work to make more complex ones.”
These more complex databases have now become staples of increasingly multi-part and sophisticated biological research. One example is the NCBI (National Center for Biotechnology Information) of the US National Institutes of Health, with its BLAST algorithm.
“BLAST connects to the repository of all the genetic data of the NCBI,” Reyes explains. “Different institutions from the US, Japan and Europe formed a consortium to ensure that whatever data they have is available to the outside world. ?So, everyone’s seeing the same thing.”
In principle, whenever an experimenter from anywhere in the world sequences a gene (or a genome), one can always use BLAST to look up similar ones within the database. “That way,” Reyes says, “you can identify your gene or your protein, or make an intelligent guess as to its structure or function.” The process applies even to other types of molecular data, such as mass spectrometry fingerprints for proteins and metabolites.
A many-part machine
The need for an in-house database that is comprehensive and easy to use becomes obvious, given the scale and complexity of Reyes’s project. Communicating mostly over Skype, each of his fellow researchers in the Glycoproteomics of Filipino Lung Cancer Cell Lines for Biomarker Discovery and Anti-Cancer Screening of Natural Products team makes unique data contributions, working autonomously on components that, in sum, contributes to the achievement of broader aims.
In total, the project lays the foundation for future research that will allow clinicians to profile a patient and tell, in the shortest time possible, whether he or she has lung cancer, and what therapeutic regimen might be most effective. It will also help us develop drugs that target multiple genes, tailored specifically to the local population.
One component of the project, headed by Dr. Francisco Heralde of the Lung Center of the Philippines, will collect tumor tissue and blood samples from Filipino lung cancer patients, and establish cell lines for them.
Why is this important? Reyes says the majority of work done on lung cancer so far has used European and American samples. “We have our own sets of mutations, our own genetic profile.” And these samples will both help establish?if Filipinos do indeed have unique cancer biomarkers, and help clarify how we might respond differently to therapies, given these profiles.
In another component, researchers will be using techniques offered by the UC Davis laboratory of Dr. ?Carlito Lebrilla, an expert in glycosylation—the attachment of carbohydrates to molecules like proteins. Some of these “glycoproteins” in turn perform functions vital to the cell, such as sending and receiving signals.
Lebrilla’s team found out that several types of cancers could be differentiated by analyzing the types and abundance of these carbohydrates or “glycans.” Profiles of these glycans in collected patient samples will be made, in addition to profiles of genetic variation and gene expression to determine how glycosylation errors come about and how these might be diagnostic “markers” which future therapies can target.
The third component, led by chemists Dr. Ruel Nacario and Dr. Gladys Completo from UP Los Ba?os, in collaboration with Dr. Isagani Padolina of Pascual Pharma Corp. R&D Lab will characterize and identify plant extracts from the Makiling area that can help prevent or treat lung cancer. Compounds isolated from these plants will be screened for bioactivity against known cancer cell lines, and those previously collected. A computational team, including Reyes and led by mathematician Dr. Jomar Rabajante, will also try to model the broader cancer network involving genes, their expression, and the interactions between them based on all the collected data.
Underpinning all these efforts and constantly fed by information produced by team members will be the project’s database. And while access to this invaluable repository might be limited to the team at this time, it will be available to the world once the project is complete.
Thinking in systems
For Reyes, advances in technology have irrevocably changed how science is done. Databases like BLAST, KEGG and the one he is helping build, now allow scientists to think bigger and bridge disciplines once considered distinct.
“Nowadays, we cannot live in isolation,” he says. “In order to solve scientific questions, you probably have to have a multi-disciplinary team like our project does. It’s invigorating to be in the middle of such a team.” For Reyes, this multidisciplinary and collaborative approach is key to sustaining local scientific progress.
Reyes expects their effort to soon be joined by younger researchers, trained from high school onwards to think more broadly about scientific problems. “I don’t know how biology in high schools is taught now, but I think it should include a sense of thinking in systems. That there is so much more beyond the textbook.” On this note, organizations such as the US-based Institute for Systems Biology are introducing systems biology concepts to K-12 students there.
If applied in the Philippines, this orientation should produce versatile students that are better prepared for the interdisciplinary and data-driven nature of contemporary research. And when they graduate, the database prepared by Joeriggo Reyes and his colleagues should be there to help that generation’s brightest to make their own breakthroughs.