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Biophysics Collaborative Access Team

Thomas Irving, Ph.D.
P41RR008630
Active

Center Overview

The Biophysics Collaborative Access Team (BioCAT) operates undulator beamline 18ID at the Advanced Photon Source, Argonne National Laboratory. BioCAT's mission is to provide a national research resource for using X-ray diffraction, scattering and spectroscopic imaging technologies for the study of partially ordered biological molecules, complexes of biomolecules, and cellular structures under conditions similar to those present in living cells and tissues. The goal of this research is to understand the detailed mechanisms of action of such systems at the molecular level. Health issues that are directly addressed are the function and regulation of skeletal and cardiac muscle; collagenous structures and interactions with collagen binding proteins that have roles in heart disease and cancer; structure of amyloids, neurofibrillary tangles, metal metabolism and relationship to neurodegenerative disease. Basic biomedical questions that are addressed include the structure and dynamics of macromolecular complexes in solution, kinetics of protein and RNA folding, and roles of metal metabolism in development. The techniques employed are small- and wide-angle x-ray diffraction, x-ray solution scattering and x-ray absorption/emission spectroscopy with micro-beams. The BioCAT facilities provide a resource that is unique on the continent; only SPring-8 in Japan and the ESRF in France provide similar capabilities. Ongoing core developments are in the areas of:

  1. Time and spatially resolved Fiber Diffraction for study of muscle, connective tissues, viruses, and structures associated with neurodegenerative diseases.
  2. Expanded Q-range, high-time resolution and high-throughput Small-Angle X-ray Scattering (SAXS) for the study of the low resolution structure of macromolecules in complexes, determination of protein folds in small proteins and domains and time resolved studies of protein and RNA folding.
  3. High efficiency x-ray florescence microprobe for studies of metal mapping, speciation and local structure as related to cancer, development, and neurodegenerative diseases.

Impact on Human Health

Many of the experiments done at BioCAT are directed at fundamental biophysical mechanisms of how molecules, cells and tissues work, from mechanisms of protein folding, to regulation of muscle tissues and the arrangement of collagen fibers and their interaction partners in the extracellular matrix. Knowledge gained from such studies provide interpretive frameworks for the roles of these materials in both health and disease. Within this diversity, many BioCAT projects are focused in one of three areas, namely heart disease, cancer, and neurodegenative disease. X-ray diffraction studies of cardiac muscle inform our understanding of heart failure and familiar cardiomyopathies resulting from point mutations in myfilament proteins. Diffraction studies of collagen have yielded insights into mechanisms of proteolysis associated with metastic tumors. X-ray florescent microscopy studies have helped understand the mechanism of action of copper sequestering anti-cancer drugs. Diffraction studies of tau bodies and amyloid structures and X-ray florescence mapping studies of diseased brain tissue yield insights into neurodegenerative diseases such as Parkinson's disease and Alzheimer's.