Lighting the Way to Better Understanding of the Brain
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specific genes in the genome in a spatiotemporally defined pattern are just one of many systems governing brain function. A hairball-like network of genes and regulatory proteins invites simple mutations to amplify and explode in their effects on health and brain function.
This system of DNA and protein is vulnerable to the influence of external environmental factors (like toxic fumes and diet), and in turn, it is part of a larger system of proteins, specialized brain cell types and neural networks.
Cell types and neural networks form a system that enables information transfer within and among regions of the brain, and this crosstalk governs myriad other processes in the body.
Whether something is awry at the genetic, protein or neural network level, the result can be debilitating.
The gauntlet is twofold: Where in the brain’s systems is the problem located, and what’s the best way to target the problem for improved health? Systems biologists work from the idea that we need to understand the biology of each brain system, and we need to know how those systems work together at multiple scales. In short, we need the candles, and we also need to light the space among them.
To do this, systems biology combines rigorously tested biological concepts with new discoveries from massive datasets collected at all levels within the brain – genes, regulatory networks, proteins, and cells. In an iterative cycle of biological inquiry, technology development, and computational modeling, new and old data are integrated using algorithms that are guided by existing biological knowledge to make new discoveries while gaining a clearer picture of how all the systems work together.
For example, the Allen Brain Atlas is a trove of mRNA measurements at 60,000+ genetic loci, from ~1,000 locations throughout the brain. This RNA-level resource was integrated with spatial anatomical data and cell-type information to reveal cell-specific proteins.
The punchline is that a few of these cell-specific proteins are present in peripheral blood, and may act as sentinels or biomarkers of an individual’s current or future disease symptoms. Disease phenotypes could be traceable, through blood proteins, to a single cell type in the brain.
Integrative neurobiology research like this is increasingly common, and requires intensive cross-disciplinary collaboration among biologists, engineers, physicians, and computer scientists. The President’s intention to back a decades-long effort to map the activity of the entire human brain is a timely testament to the need for this new A-game in brain science.
Critics doubt that current technology and resources can handle the task of producing value-adds for the steep $3 billion price, and thus the pace of new technology development and collaborative innovation will determine when and if the challenge is met.
Obama’s proposal aside, systems biology is the science of breaking down and making sense of complexity, for better health and better environmental stewardship. The brain is complex, but more importantly it’s personal and in a league of its own among organs. We have much to gain from bringing systems biology to bear on its mysteries.
The upcoming symposium on systems biology and the brain at Seattle’s Institute for Systems Biology will highlight new advances and will foster a dialogue on deciphering even more of the brain’s complex secrets. The light in the auditorium is dim now, but it brightens every day.