Mitochondria are membrane-bound organelles found in most eukaryotic cells. In addition to serving as the energy generator and distributor in cell metabolism, they play important signaling and regulation roles in many other essential biological processes. To serve the changing needs of dynamic cellular processes, mitochondria frequently undergo shape change and spatial redistribution. Mitochondria shape change is achieved primarily through fusion and fission and in mammalian cells is mediated by a number of fusion and fission proteins. Mitochondria spatial redistribution is achieved primarily through their active transport, including long distance transport by microtubule-associated motor protein kinesin and dynein and their short distance transport by actin-associated protein myosin. Mitochondria dynamics is critical to cellular function and is under tight regulation. Quantitative characterization of mitochondrial dynamics is critical to understanding mitochondria function and regulation, which, in turn, is critical to understanding cell metabolism and other related essential cellular and organismal processes.
The main goal is to study the relation between the two essential aspects of mitochondria dynamics, namely shape change and spatial redistribution, by analyzing mitochondria shape under different genetic perturbations of kinesin and dynein in axonal transport of 3rd instar Drosophila larvae. Drosophila genetics provides a powerful tool for specific manipulation of different kinesin and dynein subunits that serve different functions in mediating mitochondria transport. Specific aims include the application of shape description approaches to characterize axonal mitochondria shapes and to correlate with the underlying genetic background of motor protein mutation; the application of shape change metrics to quantify dynamic mitochondria shape variations over time and to correlate with the underlying genetic background of motor protein mutation; and the application of pattern classification and machine learning techniques to correlate mitochondrial shape with functions of motor protein subunits.
Eighty time-lapse fluorescence videos of mitochondria transport in dissected Drosophila larvae have been collected in wild type Mito-GFP flies and in several motor mutants. Video data will be analyzed to produce 2D point clouds describing mitochondria movement and distribution as well as 2D meshes describing individual mitochondria shape.
Yang G. (2014) Image-based computational tracking
and analysis of spindle protein dynamics, in Mitosis: Methods and Protocols, Methods in Molecular Biology, D. Sharp ed., vol. 1136, DOI 10.1007/978-1-4939-0329-0_5, Springer.
Gunawardena S., Yang G., and Goldstein L. S.
B. (2013) Presenilin controls kinesin-1 and dynein function during AP vesicle transport in vivo, Human Molecular Genetics, vol. 22, pp. 3838-3843.
Yang G. (2013) Bioimage informatics for understanding
spatiotemporal dynamics of cellular processes, Wiley Interdisciplinary Reviews Systems Biology and Medicine, vol. 5, pp. 367-380.
Booth-Gauthier E. A., Alcoser T. A., Yang G., and
Dahl K. N. (2012) Force-induced changes in subnuclear movement and rheology, Biophysical Journal, vol. 103, pp. 2423-2431.
Reis R. F., Yang G., Szpankowski L., Weaver
C., Shah S. B., Robinson J. T., Hays T. S., Danuser G., and Goldstein L. S. B. (2012) Molecular motor function in axonal transport in vivo probed by genetic and computational analysis in Drosophila,Molecular Biology of the Cell, vol. 23, pp. 1700-1714.
Chen K.C., Yang G., and Kovacevic J. (2014)
Spatial density estimation based segmentation of super-resolution localization microscopy images, Proc. 2014 IEEE International Conference on Image Processing (ICIP), to appear.
Chen K.C., Qiu M., Kovacevic J., and Yang G.
(2014) Computational image modeling for characterization and analysis of intracellular cargo transport, Proc. of CompIMAGE'14, to appear.
Lee H.-C. and Yang G. (2014) Integrating dimension
reduction with mean-shift clustering for biological shape classification,Proc. 2014 IEEE International Symposium on Biomedical Imaging (ISBI), pp. 254-257.
Chen K.-C. Kovacevic J., and Yang G. (2014)
Structure-based determination of imaging length for super-resolution localization microscopy, Proc. 2014 IEEE International Symposium on Biomedical Imaging (ISBI), 991-994.
Yang G. and Olivo-Marin J.-C. (2013) Image-based
representation and modeling of spatiotemporal cell dynamics, Proc. 2013 IEEE International Symposium on Biomedical Imaging (ISBI), pp. 1198-1201
Qiu M. and Yang G. (2013), Drift correction
for fluorescence live cell imaging through correlated motion detection, Proc. 2013 IEEE International Symposium on Biomedical Imaging (ISBI), pp. 452-455
Chen K.-C., Yu Y., Li R., Lee H.-C., Yang G.,
and Kovacevic J. (2012), Adaptive active-mask image segmentation for quantitative characterization of mitochondrial morphology, Proc. 2012 IEEE International Conference on Image Processing (ICIP), pp. 2033-2036
Qiu M., Lee H.-C., and Yang G. (2012), Nanometer
resolution tracking and modeling of bidirectional axonal cargo transport,Proc. 2012 IEEE International Symposium on Biomedical Imaging (ISBI), pp. 992-995
Yang G. (2011) Nanometer resolution imaging
and tracking of axonal cargo transport in normal and degenerative neurons (invited paper), Proc. 45th Annual Asilomar Conference on Signals, Systems, and Computers, pp. 431-435.
Hongfei Cao; Jing Han; Chi-Ren Shyu, "Object
behavior mining from mitochondiral shape databases for degenerated nerve disease studies," IEEE International Conference on Bioinformatics and Biomedicine (BIBM), pp.7,9, 18-21 Dec. 2013, doi: 10.1109/BIBM.2013.6732743
Project Members:
Dr. Ge YangDr. Chi-Ren Shyu
Project Description:
Mitochondria are membrane-bound organelles found in most eukaryotic cells. In addition to serving as the energy generator and distributor in cell metabolism, they play important signaling and regulation roles in many other essential biological processes. To serve the changing needs of dynamic cellular processes, mitochondria frequently undergo shape change and spatial redistribution. Mitochondria shape change is achieved primarily through fusion and fission and in mammalian cells is mediated by a number of fusion and fission proteins. Mitochondria spatial redistribution is achieved primarily through their active transport, including long distance transport by microtubule-associated motor protein kinesin and dynein and their short distance transport by actin-associated protein myosin. Mitochondria dynamics is critical to cellular function and is under tight regulation. Quantitative characterization of mitochondrial dynamics is critical to understanding mitochondria function and regulation, which, in turn, is critical to understanding cell metabolism and other related essential cellular and organismal processes.The main goal is to study the relation between the two essential aspects of mitochondria dynamics, namely shape change and spatial redistribution, by analyzing mitochondria shape under different genetic perturbations of kinesin and dynein in axonal transport of 3rd instar Drosophila larvae. Drosophila genetics provides a powerful tool for specific manipulation of different kinesin and dynein subunits that serve different functions in mediating mitochondria transport. Specific aims include the application of shape description approaches to characterize axonal mitochondria shapes and to correlate with the underlying genetic background of motor protein mutation; the application of shape change metrics to quantify dynamic mitochondria shape variations over time and to correlate with the underlying genetic background of motor protein mutation; and the application of pattern classification and machine learning techniques to correlate mitochondrial shape with functions of motor protein subunits.
Eighty time-lapse fluorescence videos of mitochondria transport in dissected Drosophila larvae have been collected in wild type Mito-GFP flies and in several motor mutants. Video data will be analyzed to produce 2D point clouds describing mitochondria movement and distribution as well as 2D meshes describing individual mitochondria shape.
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