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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Committee Members:
Hang Lu, Ph.D. (Georgia Institute of Technology) - Thesis Advisor
Queelim Ch'ng, Ph.D. (MRC Centre for Developmental Neurobiology, Kings College London)
Robert Butera, Ph.D. (Georgia Institute of Technology)
Philip J. Santangelo, Ph.D. (Georgia Institute of Technology)
Harold Kim, Ph.D. (Georgia Institute of Technology)
Patrick McGrath, Ph.D. (Georgia Institute of Technology)
Aging is a complex process by which a combination of environmental, genetic and stochastic factors generate whole-system changes that modify organ and tissue function and alter physiological processes. Over the last few decades, many genetic components of aging have been found to be highly conserved between humans and a diverse group of model organisms. Moreover, many conserved environmental modulators of aging, including diet and temperature, have been discovered; some of the genetic targets that sense, store and translate these signals into lifespan alterations have been characterized in model organisms. Yet, an integrative understanding of how these environmental and genetic variables interact over time in a whole organism to modulate the systemic changes involved in aging is lacking. The goal of this thesis project is to advance a systems perspective of aging by providing the experimental tools and conceptual framework for dissecting the regulatory connection between environmental inputs, molecular outputs and long term aging phenotypes.
The nematode Caenorhabditis elegans serves as an extremely convenient multicellular model system for the aims of this project. Its ease of culture and genetic manipulation permit a high degree of control over both environmental and genetic factors. Moreover, its optical transparency permits minimally invasive, in vivo assessment of gene activity via the use of fluorescent reporters. Yet, the large-scale, cell-specific quantitative imaging of C. elegans necessary for this study has thus far been time-prohibitive due to the low throughput nature of conventional imaging techniques. To overcome these experimental barriers and enable this study, we develop a fully autonomous high throughput imaging platform utilizing the power of microfluidics for fine physical manipulation of the micron-scale nematode in combination with the power of computer vision to support automation and data extraction.
To address the main goals of this study, we then apply these technologies to characterize how two previously identified environmentally sensitive genes respond to food and temperature manipulation. By assessing aging phenotypes such as reproductive capacity and longevity under the same conditions, we hope to establish these two genes as functional mediators of the regulatory relationship between environmental manipulation and phenotypic changes. With this quantitative understanding of how environment alters the molecular code underlying aging, we will then explore how noise in these molecular signals may contribute to the observed variability in the aging process. Our underlying hypothesis is that knowledge of a subset of gene expression variables responsible for the translation of environmental inputs into aging phenotypic outputs will allow us to have predictive power of the aging trajectory of an animal.
