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Molecular medicine in four dimensions

Revolutionary advances at the Center for Spatial Systems Biomedicine

The OHSU Center for Spatial Systems Biomedicine (OCSSB) is dedicated to elucidating the structural and mechanical properties of cells and tissues, understanding how these structures are encoded and regulated by genomic features and how genomic aberrations corrupt aspects of structure that lead to disease formation. 

OCSSB scientists will accomplish this by combining information from advanced genome and molecular component analyses with three dimensional structural information obtained using revolutionary imaging technologies that reveal structural details across size scales ranging from Angstroms to nanometers to centimeters, across anatomical sites and over time scales ranging from microseconds to days.

The OCSSB will build on decades of research that have revealed  the molecular components and assemblies that comprise normal cells and tissues as well as how (epi)genomic abnormalities alter these components in diseases ranging from cardiovascular disease to cancer. 

The OCSSB now seeks to develop the three dimensional "assembly manuals" that enable the normal and aberrant functions of molecular assemblies, cells and tissues and to learn  how these compositions vary over time and anatomic location -- in short to develop the field of four dimensional medicine (3 spatial dimensions and time). 

A long term goal of the OCSSB is to exploit this four dimensional understanding to improve disease diagnosis and treatment.

A integrated program in multiscale molecular analysis

The Center for Spatial Systems Biomedicine is developing a comprehensive program focusing on the genomics of molecular, cellular and tissue structures and is comprised of faculty with expertise in multiple aspects of spatial systems biology including:

  1. Genome science to elucidate details of normal and aberrant genome form and function,
  2. Three dimensional measurement technologies enabling imaging at scales ranging from Angstroms to cm,
  3. Reporter chemistry and cell and tissue engineering to enable visualization and quantitative analysis of specific molecular machines in cells, tissue and living animals,
  4. Multiparameter data management, visualization and modeling,
  5. Development of laboratory disease models that capture the complexity and diversity of human disease function in anatomic context.

The latter is particularly important in cancers that present with a broad range of molecular features and exist in and respond to therapy in a broad range of chemical, mechanical and molecular microenvironments.  OCSSB will support a robust and continuously evolving measurement science research infrastructure encompassing technology, biology, chemistry and computational biology.

Multiple research programs linking clinical and basic science

The OCSSB engages multiple research programs and links clinical and basic science to address the most pressing and important biomedical questions:

  • Cancer — How can we tailor treatment to individuals? How can we discover robust therapeutic strategies faster and cheaper? How can we detect agressive tumors earlier when they are more easily treated? Why is metastatic disease so resistant to treatment? How does the microenvironment influence therapeutic response and can we develop microenvironment independent therapeutic approaches?
  • Neurobiology — What contributes to the structural and functional basis of specific neural circuits involved in normal and maladaptive neurophysiological processes? How can we identify and map neural connections involved in acute and chronic pain, addiction and reward? How can we evaluate the cellular consequences of promising agents of neurorescue, neurorepair, or neuroprotection?
  • Cardiovascular disease — Why do non-communicable diseases, such as obesity, diabetes and cardiovascular disease, develop in some but not all individuals? Why do some cardiovascular diseases "run in the family"? How can we predict the beneficial as well as adverse effects of new drugs at the gene and metabolite level?
  • Immunology and Infectious Disease — What are the molecular requirements of virus entry into host cells? How can we tailor new drugs to interfere with the molecular machinery of viral assembly? How can we boost immune strategies that work against intracellular pathogens? How can we detect the molecular basis of autoimmune induced disease?

Utilization of advances in measurement science

The OCSSB will use advances in measurement science to learn how the molecular components being discovered today function, how abnormalities in these contribute to disease characteristics and to use the resulting information to improve disease management.  Planned instrumentation will include cryoelectron electron microscopy for Angstrom level resolution, scanning electron microscopy and super resolution light microscopy for nanometer level resolution, confocal light microscopy and scanned ion beam mass spectrometry for micrometer level resolution and positron emission tomography and X-ray computed tomography for millimeter level resolution as well as high content, high throughput imaging for high throughput, structure oriented biology.

OCSSB: multi-disciplinary, multi-departmental and multi-institutional

The Center for Spatial Systems Biomedicine is multi-disciplinary, multi-departmental and multi-institutional. The program is centered at OHSU but includes activities at Portland State University, and Oregon State University, local technology centers in nanotechnology and drug discovery.  It interacts broadly with partners from the biotechnology and pharmaceutical industries as well as multiple leading academic institutions.