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Investigating Biochemical Interactions Relevant To Human Health Using Backscattering Interferometry

dc.creatorOlmsted, Ian Roys
dc.date.accessioned2020-08-22T17:21:38Z
dc.date.available2015-07-17
dc.date.issued2013-07-17
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-07112013-100810
dc.identifier.urihttp://hdl.handle.net/1803/12918
dc.description.abstractThis 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.
dc.format.mimetypeapplication/pdf
dc.subjectAllosteric Interactions
dc.subjectBiomarker Validation
dc.subjectBioanalytical
dc.subjectBackscattering Interferometry
dc.subjectBSI
dc.titleInvestigating Biochemical Interactions Relevant To Human Health Using Backscattering Interferometry
dc.typedissertation
dc.contributor.committeeMemberErik P. Skaar
dc.contributor.committeeMemberDavid W Wright
dc.contributor.committeeMemberJohn A. McLean
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineChemistry
thesis.degree.grantorVanderbilt University
local.embargo.terms2015-07-17
local.embargo.lift2015-07-17
dc.contributor.committeeChairDarryl J Bornhop


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