Systems Biology at Pacific Northwest National Laboratory
Changes in translational efficiency can explain poor correlation between changes in mRNA levels and protein expression
The contribution of transcription (vertical axis) vs. translational efficiency (horizontal axis) is compared to protein expression changes. The widespread change shows that transcription is not the sole determinant of altered protein levels. Click for a larger version.
Changes in gene expression are not always accompanied by corresponding alterations in protein levels, especially in microbial systems. PNNL scientists now show that this is frequently due to widespread changes in the translational efficiency of specific mRNAs caused by alterations in functional tRNA pools. This understanding was obtained by using mathematical modeling to understand integrated RNA-Seq and quantitative global proteomics data sets.
Systems biology at PNNL is focused on understanding gene and protein networks involved in individual cell signaling, communication between cells in communities, and cellular metabolic pathways. Our systems biology research program is driven by programs in the Fundamental & Computational Sciences Directorate (FCSD) and EMSL, a national user facility located at PNNL, as well as by collaborations with researchers around the world.
Not only are these capabilities being applied to problems of national/international importance, but they are available to outside users.
Talented Multidisciplinary Teams
The integrated talents of our multidisciplinary research teams lend strength to our systems biology research. Our biologists, microscopy experts, and proteomicists study the thousands of proteins and/or other cellular components, which are regulated through variations in their location, their activity, and their state of modification. Our bioinformaticists and computational biologists 1) work with bench scientists to integrate high-throughput instruments into a computational infrastructure; (2) create models of cellular networks appropriate for inferring the structure and function of cellular networks from large volumes high-throughput, heterogeneous data; and (3) develop software to aid visualization and interpretation of this flood of data.
The methods we are developing to integrate and interpret high-throughput, quantitative data will serve as a foundation for creating predictive models of cellular responses and functions.
A Strong Technical Infrastructure
Advanced instrumentation and technologies at both PNNL and EMSL provide a strong technical infrastructure for our systems biology research. We combine world-class
- High-throughput proteomic tools
- Sequencing technologies
- Precise analytical methods
- Multimodal imaging capabilities
- Sophisticated computational tools
to characterize and model cells responding to environmental changes, interrogating their surroundings, and communicating with other organisms in communities.
Applying Systems Biology to Problems of National Interest
We apply our systems biology methods to and enhance our systems biology capabilities through a variety of research areas, including cellular responses to oxidative stress and radiation, interrogative cell signaling, network biology, cellular responses to environmental stress, biomarkers that indicate environmental contaminants and disease, biofilms, and microbial communities.
Through our research, we address problems important to the U.S. Department of Energy and the nation, including clean energy production, carbon sequestration, environmental cleanup, improved disease diagnosis and treatment, and protecting people from environmental hazards.