Baliga Lab Overview

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“It is the fundamentally important biological questions that drive the invention of new technologies. Once developed, using model organisms, these innovations revolutionize scientific investigations across all biological systems.”

–Nitin Baliga, PhD, SVP & Director
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The Baliga group develops models of biological systems, from single cells to communities of multiple organisms, that accurately predict adaptation to environmental changes. A key aspect is the combination of information from multiple levels – genes, proteins, whole cells, natural forces – to gain a clear understanding of the specific inputs and processes that lead to specific system behaviors. In doing so, the Baliga group produces advanced tools to easily perform complex experiments and facilitate navigation of the large amounts of information generated from such experiments. Through their pioneering work, the Baliga Group has established numerous collaborations to apply this methodology to wide-ranging problems from climate change to cancer. Their long-term goal is to utilize the predictive mathematical models to rationally and responsibly solve problems related to bioenergy, bioremediation, agriculture and medicine.

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Research Overview

The Baliga group builds predictive models of complex biological phenomena that can be used to guide cells in the fight against disease, the generation of clean energy, or remediation of the environment.

Behind every biological system is a complex and dynamic network of interacting parts that defines how it behaves. Depending on the size of the system, these parts can be genes, proteins, whole cells or even whole populations. Understanding how the behavior of biological systems is altered based on changes to their underlying networks is a crucial part of understanding how diseases arise and can be cured or how ecosystems fail and can be rebuilt. To do this, the Baliga group applies a systems approach, a hallmark of the field of systems biology. The underlying networks are perturbed either externally through environmental conditions or internally by altering the characteristics of network parts. The consequences of these changes are comprehensively measured throughout the system, generating rich and highly detailed data sets that can be used to study the fundamental properties that underlie all biological systems.

Much of the Baliga group’s research has applied the systems approach to the study of Archaea. Known as the “Third Domain of Life,” this group of organisms is evolutionarily distinct from bacteria like E. coli and eukaryotes such as yeast but are just as easy to work with in the lab. They also have a propensity to live in harsh environments such as acidic hot springs, thermal vents or saturated salt lakes, and their study offers intriguing insights into evolutionary mechanisms of adaptation. Recently, Baliga and his colleagues assembled a complete network model of Halobacterium salinarum NRC-1, a microbe found in saturated brine, that is able to predict how the organism will respond to new environmental changes. Part of what made this possible is a growing set of easy-to-use and advanced software tools and algorithms. Seamless integration and in-depth analysis of rich systems data are made possible by a flexible and extensible environment called Gaggle, a framework that extends the reach of individual researchers. Importantly, the techniques used to study Halobacterium are broadly applicable to other species and systems, including humans. In ongoing research, the Baliga group is now applying advanced methods to the study of brain cancer (glioblastoma multiforme). Eventually, they will gain new insights into human disease to improve prevention, diagnosis, prognosis and treatment.

Finally, Baliga devotes a substantial portion of his time to working with Seattle-area high schools. Through a collaboration of practicing scientists, science educators and district administrators, he is helping to develop innovative inquiry- and standards-based educational modules for middle and high school students. These modules, fine-tuned via high school student interns and teachers, will increase student engagement and retention in the sciences, support educators as they teach modern and accurate science, and foster the development of bright thinkers and scientists.

Research Focus

The tools and concepts of systems biology have applications that range far beyond human health. For example, systems biology can provide spectacular insights into the capacity of organisms to adapt to environmental changes over short and long time periods. Mechanisms of adaptation include mutations in single nucleotides, gene duplications or deletions, and horizontal gene transfer in single-celled organisms. These mechanisms can change the properties of a protein or rewire regulatory networks, producing both the physiological flexibility needed to counter short-term environmental changes and long-term adaptation to stable, though in some cases extreme, environments. A holistic systems approach is necessary to fully appreciate how these varied mechanisms work together when an organism adapts to a new environment. Understanding of these mechanisms also may point to regions of the genome that are more evolvable than other regions, which could be important in re-engineering single-celled organisms to solve environmental or energy problems.

Source: Brooks AN, Turkarslan S, Beer KD, Yin Lo F, Baliga NS. 2010. Adaptation of cells to new environments. Wiley Interdisciplinary Reviews: Systems Biology and Medicine.