About the OCSSB

What is Systems Biology? What is the OCSSB?

The OHSU Center for Spatial Systems Biomedicine was established in 2011 as a joint project between the Knight Cancer Institute and the School of Medicine, intended to take a step beyond the measurement of DNA, RNA and protein profiles — or omics, which collectively encompasses genomics, transcriptomics, proteomics, etc. — in helping to uncover the mechanisms that influence the behavior of normal and diseased tissues. Omic approaches are powerful because they provide both broad and precise information about the biomolecular composition of a sample. However, they are limited because they typically provide information only about the component being studied; information about spatial context is lost since tissues are separated into components before analysis. This is referred to as a reductionist approach because it reduces the study target into components for analysis. 

In contrast, a systems biology approach is constructionist. At the OCSSB we employ omics but also consider how the biological behavior of a cell is dramatically influenced by the insoluble protein, soluble protein and cellular composition of the microenvironment in which it lives. With access to cutting-edge multiscale and superresolution microscopy technologies, we are no longer limited by the inability of older measurement technologies to provide high-resolution information about protein and cellular assemblies that determine biological function, and we may examine these at multiple scales ranging from Angstroms to centimeters, or submolecular through tissue or larger units. We also can examine living tissues through time, giving us insight in four dimensions ("4D"), that is, 3 spatial dimensions and time.

Facets of the OCSSB

Studies of Complex Systems

The OCSSB enables integrated omic and spatially defined studies of complex systems ranging in size from Angstroms to millimeters. This is accomplished by:

  1. Developing and acquiring new omic and multiscale analysis technologies and imaging chemistries
  2. Using these to characterize cancers and other complex biological systems 
  3. Developing new computational methods to visualize and interpret the resulting data.

Multidisciplinary Teams 

This requires multidisciplinary teams that the OCSSB has now assembled: 

Discipline Responsibility
Biophysicists and biomedical engineers Develop new measurement platforms
Biochemists and biologists Develop new staining reagents and engineer biological systems with reporter tags to make specific molecular features visible during imaging
Image analysts Manage, display and model multiscale images
Computational biologists Integrate and link omic and image data to identify functional molecular complexes and elucidate their operational behavior
Biologists and physician scientists Develop critical biomedical projects that apply OCSSB capabilities.
Business development and intellectual property experts Develop collaborations with private sector partners, identify and manage intellectual property and support spinoff businesses.
Project managers Define milestones and monitor progress.
Administrative support Manage complex multi-department, multi-institution, public-private sector projects

Recent Technology Advances 

Remarkable recent advances in both omic and imaging technologies enable the multiscale omic/imaging studies that OCSSB investigators undertake. Advances in the field of omics (DNA, RNA and protein profiling) are widely appreciated. Advances in multiscale imaging are less widely appreciated but no less remarkable. 

Imaging capabilities now available in the OCSSB allow resolution of features ranging in size from Angstroms to centimeters. 

OCSSB Focus

The OCSSB has been developed with a significant focus on cancer. However, the analytical approaches also are being applied in neurobiology, cardiovascular research and immunology. Specific projects in cancer already established focus on elucidation of:

  1. Omic and multiscale biological architecture changes that enable the genesis and progression of cancer and other diseases
  2. The influence of omic aberrations on 3D multiscale cellular assemblies with emphasis on receptor tyrosine kinase cascades
  3. Mechanisms by which cancers escape treatment control
  4. Interactions between cancer cells and diverse microenvironment interactions that influence progression and therapeutic response
  5. Novel therapeutic approaches to treatment of drug-resistant advanced cancers. 
Neurobiologists have made especially good use of our highest resolution instruments to elucidate specific protein structures with emphasis on membrane proteins. Instruments and workflows also are made available to support research throughout OHSU and the Northwest – specifically to support fundamental studies of normal cell and developmental biology, cardio-vascular behavior and disease, immunology, neurobiology and dental materials. 

OCSSB startup 

The OCSSB was funded in two phases. Progress during the initial 3-year phase was reviewed by an external committee comprised of two members of the National Academy of Science and an internationally recognized expert in multiscale imaging. Based on that positive review, the OCSSB funding for recruitment of faculty, instrumentation acquisition and maintenance, support staff, advanced computing and administrative support was continued through 2020. Most OCSSB instruments are available as University Shared Resources through the Multiscale Microscopy Core and the Advanced Light Microscopy Core. The OCSSB is now one of the most comprehensive omic and imaging centers in the world.