Computational Biology, Systems Biology
Dr. Amaral is also a professor of chemical and biological engineering at Northwestern University and an associate professor of medicine at Northwestern University School of Medicine.
He may not be a cartographer in the traditional sense, but Northwestern University's Luís Amaral is building what could become the biologist's Google Maps. His tool—for navigating cells, not roads—would synthesize vast amounts of biological data into user-friendly "maps" that allow researchers to zoom in or out to see complicated cellular pathways at any scale of interest.
A native of Portugal, Amaral likens his efforts to those of Portuguese sailors who systematically mapped the coast of Africa in the second half of the 15th century. Like them, he's gathering information from various sources and synthesizing it to make the most useful maps possible. "As we are gathering new data, we are developing new ways to make more sense and better use of it," he says.
The cartographical approach, he explains, uses computer power and sophisticated algorithms to synthesize the avalanche of biological data that have emerged in recent decades. Biological systems, after all, are not unlike geographical ones in terms of how they are organized. Just as continents have countries, with states and localities within, an organism is composed of organs, which have tissues, which are made of cells, which themselves contain genes, proteins, and other molecules.
In many cases, the sheer volume of new information about these systems has overwhelmed the research community's ability to explain how the smallest parts of an organism work together to create the whole.
In 2005, Amaral published a landmark paper that mapped the metabolic pathways that allow cells to store and use energy. The cells came from 12 organisms, four each from the three domains of life (archae, bacteria, and eukaryotes). The paper was the first to analyze complex networks using a cartographic approach.
Amaral chose the metabolic system because its parts—if not the complete picture—were already well understood. More than 1,000 chemicals involved in digestion, known as metabolites, are connected by several thousand reactions inside a human cell. To identify the most important parts of that system—the capital cities and major interstates, so to speak—Amaral looked for so-called "connector" metabolites, which serve as hubs for multiple chemical pathways.
Amaral's maps showed that these key connector molecules are quite rare, comprising less than 10 percent of all metabolites. Moreover, he found that the metabolites his maps identified as "connectors" are highly conserved across species, meaning they are the same, in a bacterium and in a more complex organism. Ordinary metabolites, by contrast, can vary widely between species. Sometimes they exist in one type of organism but not in another.
In his current project, Amaral is designing a tool that will "map" the metabolic pathways of a commonly studied model organism, the bacterium Escherichia coli. His goal is to enable anyone to go online and tinker with hypothetical conditions to see how the bacterium might respond, based on what is already known about it. It would, in theory, allow researchers to test ideas—zoomed in on individual metabolites or zoomed out on complete cellular pathways—without the time and cost of laboratory experiments.
Amaral intends to build gradually on the metabolism model. "We hope to climb up the ladder from metabolism to gene regulation, protein interactions, and translation and transcription, but it will take a while," he says. "Once the infrastructure is firmly in place, it should be easier to put in [new] data."