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Title page for ETD etd-07112013-100810


Type of Document Dissertation
Author Olmsted, Ian Roys
URN etd-07112013-100810
Title Investigating Biochemical Interactions Relevant To Human Health Using Backscattering Interferometry
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Darryl J Bornhop Committee Chair
David W Wright Committee Member
Erik P. Skaar Committee Member
John A. McLean Committee Member
Keywords
  • Allosteric Interactions
  • Biomarker Validation
  • Bioanalytical
  • Backscattering Interferometry
  • BSI
Date of Defense 2013-06-25
Availability unrestricted
Abstract
This project is concerned with the characterization of biomolecular interactions that are pertinent to human health using backscattering interferometry (BSI). In this dissertation, I used the unique ability of BSI to measure binding events in tethered and free-solution formats to quantify the effect that surface immobilization has on carbohydrate-lectin binding affinities. This work helps to explain the large discrepancy commonly observed when comparing free solution measurements such as isothermal titration calorimetry (ITC) with surface plasmon resonance (SPR). I also demonstrated the utility of BSI in measuring allosteric interactions of protein-aptamer binding systems as well as lipoparticle-based ligand-receptor binding. This work validates the hypothesis that the CXCR4 receptor, once thought to bind the CXCL12 ligand exclusively, binds non-native ligands as well. A better understanding of neuroreceptor function will no doubt aid in future drug therapy development. Finally, I used BSI to quantify unknown concentrations of disease-specific biomarkers in complex matrices such as serum (Cyfra 21-1 and Galectin-7) and cell lysate (respiratory syncytial virus). I was able to quantify lung cancer biomarkers at levels that are up to 40-fold lower than current commercially available technologies. This work validated BSI as a biomarker quantification tool and paves the way for eliminating the bottleneck in clinical validation. In the long term, rapid, low-volume, highly sensitive, label-free, immobilization-free biomarker validation will enable personalized medicine and improve clinical outcomes.
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