dc.creator | Olmsted, Ian Roys | |
dc.date.accessioned | 2020-08-22T17:21:38Z | |
dc.date.available | 2015-07-17 | |
dc.date.issued | 2013-07-17 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-07112013-100810 | |
dc.identifier.uri | http://hdl.handle.net/1803/12918 | |
dc.description.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. | |
dc.format.mimetype | application/pdf | |
dc.subject | Allosteric Interactions | |
dc.subject | Biomarker Validation | |
dc.subject | Bioanalytical | |
dc.subject | Backscattering Interferometry | |
dc.subject | BSI | |
dc.title | Investigating Biochemical Interactions Relevant To Human Health Using Backscattering Interferometry | |
dc.type | dissertation | |
dc.contributor.committeeMember | Erik P. Skaar | |
dc.contributor.committeeMember | David W Wright | |
dc.contributor.committeeMember | John A. McLean | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Chemistry | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2015-07-17 | |
local.embargo.lift | 2015-07-17 | |
dc.contributor.committeeChair | Darryl J Bornhop | |