Research

Areas of Focus

The Ghazi Lab is currently focused on the following two key areas of research.

Proteasomal Modulation of Aging Pathways

The programmed destruction of regulatory proteins by the proteasome pathway is widely used for controlling many important biological processes including aging. Previously, we discovered that the proteasomal pathway regulates aging in C. elegans. In mutants of the insulin/IGF-1 receptor daf-2, which live twice as long as normal worms, proteasomal E3 ligases are recruited for the ubiquitination and likely degradation of cellular proteins that inhibit longevity. Current research in our lab is focused on the identification of such E3 ligase substrates whose degradation is essential for lifespan extension.

The intertwined worm and proteasome in this schematic represents the significance of C. elegans as a tool to study the role of the proteasomal pathway in controlling the rate of aging.
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Normal, fertile worms with an active germline have a normal lifespan (top). When the germline is removed from the gonad, transcription-regulatory proteins called DAF-16/FOXO and TCER-1 get activated in intestinal cells and lifespan is extended (bottom).
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Reproductive Control of Aging

Aging and reproduction are two fundamental aspects of an individual's life, and the intersection of these processes is an exciting research topic in its own right. Traditionally research has focused on the lamentable loss of reproductive capacity brought on by increasing age. However, recent discoveries in worms, flies and mice have shown that signals from reproductive tissues influence aging as well.

In C. elegans, removal of a population of reproductive cells called Germline Stem Cells (GSCs) extends lifespan. This lifespan extension is brought about by activation of multiple transcription factors in intestinal cells, including a conserved pro-longevity determinant called DAF-16/FOXO and a transcription elongation factor called TCER-1. Our research aims to study these genes and other genes and molecules that transmit signals from reproductive GSCs to the somatic tissues and thus control aging. We are actively involved in the molecular dissection of a network of transcriptional regulators that appears to extend worm lifespan in response to reproductive stimuli.

Last Update
January 14, 2012

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