It has long been thought that mitochondrial defects play an important role in the development and progression of cancer. Many of the cell growth and survival pathways targeted by anti-cancer drugs are mediated through mitochondria. However, it is not known how changes in mitochondrial shape and organization can lead to cancer, or how the altered form of cancer cell mitochondria can be exploited for therapeutic benefit.
By better understanding mitochondrial biology in cancer, they hope that knowledge from their research may contribute towards the design of new strategies for cancer prevention, diagnosis, and potential treatments.
Mitochondria, small organelles found in a cell, are complex networks that are highly variable, both between cell lines and within cell populations. They play a variety of important roles in cell physiology, such as regulating cellular processes and cell death.
Mitochondria undergo dramatic changes as cells grow, divide, and die, and mutations that affect mitochondria can affect the cell's sensitivity to stimuli. However, the relationship between mitochondrial structure and function remains unclear.
"I began working with the Opera® system as a postdoctoral fellow at Harvard, and wanted to bring the same technology to the ICR at London because I believe it is really the only microscope on the market that is capable of generating high quality images in high throughput."
Capturing Anti-Cancer Drug-Related Texture and Morphology Changes
To measure diverse changes in mitochondria as cells are exposed to different anti-cancer drug compounds, Dr. Bakal and Dr. Sero use the Opera® High Content Screening System for imaging and the Columbus™ Image Data Storage and Analysis System for analysis of mitochondrial structures. "I had used the Opera system in a previous laboratory," said Dr. Bakal, "and wanted to bring the same technology to my current research because I believe it is really the only microscope on the market that is capable of generating high quality images in high throughput."
The Opera System enables Dr. Bakal and Dr. Sero to capture high-quality images rapidly, and in high throughput. By pairing it with the Columbus system, which provides high-volume image data storage and analysis, they are able to detect any subtle changes in the mitochondria. Hundreds of texture and morphological parameters such as cell area, roundness, length, width and symmetry are typically measured.
Raising the Standard for Future Research with Their Discoveries
Dr. Bakal and Dr. Sero have found that using the Opera and Columbus systems for analysis let them distinguish not only the effects of different compounds on mitochondrial organization, but also the effects of two doses of the same drug. They have also showed that automated image analysis enables detection of more subtle changes in cells than human observers can find. Their methods will allow other researchers to analyze the degree of heterogeneity within groups, to detect subpopulations, and to measure the percentage of cells that are affected by the compounds being studied.
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