Fundamental biological processes, such as programmed cell death, cell differentiation and cell division, involve time-dependent dynamic alterations in the structure of subcellular units, the organelles. These structural changes are controlled by important molecular pathways, and must be quantified to gain a more complete understanding of cellular function. The microscopic instrument developed in this project will rapidly image and quantify, with nano-metric sensitivity, organelle dynamics. The method utilizes a dark-field microscopic method developed by the Principal Investigator, and allows rapid mapping of subcellular structural changes by automatically probing and quantifying local sample texture with very high sensitivity, and over large sample areas. The technique is therefore applicable to rapid screening of unstained biological samples for basic biological research or drug discovery. The instrument is also likely to reveal novel subcellular dynamics by enabling highly sensitive measurement of dynamic organelle changes as part of routine microscopic observation. Data collected with the instrument may be combined with molecular imaging data to provide a multimodal study of organelle function within living cells. The usefulness of the instrument to biological research will be demonstrated by measurements of mitochondrial fission during apoptosis. Mitochondria are being increasingly recognized as significant players in a number of cellular processes, including diseases such as cancer. As such, structural markers that can track changes in mitochondrial shape due to the deregulation of fusion and fission are likely to have a wide-raging impact on a number of emerging biological studies. This instrument development project exemplifies the principle that engineering design is prevalent in methods, which enable measurement, understanding, and control of biological entities, and will be used in various educational and training activities involving students at the postdoctoral, graduate, and undergraduate levels, as well as under-represented minorities from local public middle schools and high schools.
|Effective start/end date||6/1/09 → 5/31/11|
- National Science Foundation (National Science Foundation (NSF))