Purdue_University_Thesis_Rui_Yan_final.pdf (50.13 MB)
The Development of Image Processing Algorithms in Cryo-EM
Cryo-electron microscopy (cryo-EM) has been established as the leading imaging technique for structural studies from small proteins to whole cells at a molecular level. The great advances in cryo-EM have led to the ability to provide unique insights into a wide variety of biological processes in a close to native, hydrated state at near-atomic resolutions. The developments of computational approaches have significantly contributed to the exciting achievements of cryo-EM. This dissertation emphasizes new approaches to address image processing problems in cryo-EM, including tilt series alignment evaluation, simultaneous determination of sample thickness, tilt, and electron mean free path based on Beer-Lambert law, Model-Based Iterative Reconstruction (MBIR) on tomographic data, minimization of objective lens astigmatism in instrument alignment and defocus and magnification dependent astigmatism of TEM images. The final goal of these methodological developments is to improve the 3D reconstruction of cryo-EM and visualize more detailed characterization.
Funding
NIH grant (1R01AI111095)
NIH grant (1U01NS110437)
History
Degree Type
- Doctor of Philosophy
Department
- Biological Sciences
Campus location
- West Lafayette
Advisor/Supervisor/Committee Chair
Wen JiangAdditional Committee Member 2
Richard KuhnAdditional Committee Member 3
Daisuke KiharaAdditional Committee Member 4
Leifu ChangUsage metrics
Categories
Keywords
cryo electron microscopycryo electron tomographyimage processing algorithmsBeer-Lambert Lawalignment accuracythickness determinationmean free pathinelastic scatteringleast square methodsModel-Based Iterative Reconstructioncontrast improvementmissing wedge artifacts reductionmissing information restorationsubtomogram averagingastigmatism correctionobjective lens stigmatorssingle-pass tuning strategydefocus-dependent astigmatismmagnification-dependent astigmatismBiophysicsStructural BiologyComputational Biology