Gottschling, Daniel

Faculty Profile

First Name: 
Last Name: 
[field_fname-formatted] [field_lname-formatted]
Primary Institution: 
Basic Sciences
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Office Location: 

Fred Hutchinson Cancer Research Center
1100 Fairview Ave. N., A3-209
Seattle, WA 98109

Office Phone: 
(206) 667-4494

Research Summary: 


Dissecting the cellular aging process

The majority of prevalent non-infectious diseases are associated with age, yet the mechanism by which these diseases dramatically increase with age is unclear. A number of intellectually attractive hypotheses to explain age-associated decline have been generated by studies in model organisms. While there is a general consensus that accumulation of cellular damage is the basis for this decline, a molecular mechanism for what actually causes aging in any organism remains elusive.

Our overarching goal is to identify the molecular changes that cause aging, as well as the downstream age-associated events that lead to cellular decline. The budding yeast Saccharomyces cerevisiae is a great model system for studying the aging process in eukaryotic cells. With each asymmetric cell division of this budding yeast, the vitality of a “mother” cell declines, and its limited replicative life span has been used as a model to identify and study conserved genetic and environmental processes that contribute to aging in metazoa. The use of budding yeast to study aging has not been fully exploited because of the difficulty in isolating replicatively aged cells. We recently overcame this limitation by developing a technique called the Mother Enrichment Program (MEP – Lindstrom & Gottschling, 2009) that allows us to isolate and examine large populations of synchronously aged cells.

Viewing aging through the lens of interconnectivity

Our approach to studying aging considers the process in light of a fundamental property of biological systems – interconnectivity. All levels of interaction contribute to the ultimate phenotype of an organism: interactions between tissues, cells, organelles, metabolic pathways, genes, and individual molecules. With the help of network analysis, the complexity of such interactions can be visualized to develop new ideas and hypotheses about the aging process. For instance, if we examine a network of interactions within a cell and consider each organelle as a subsystem within the network, then what happens to the other connected organelles when one becomes dysfunctional with age? If a subsystem decays with age and does indeed affect a connected organelle, which interactions are required for this to occur? This simple idea focuses upon connections that create interdependency between two subsystems – e.g. one organelle produces a molecule required for the proper function of another organelle. However, in considering a network of interactions it is likely that more than one subsystem is sensitive to aging, possibly through distinct routes. Dissecting how these types of events occur is critical to developing a better understanding of aging. 

Short Research Description: 
Using yeast to study the aging process.
Areas of Interest: 
Cell Signaling & Cell/Environment Interactions
Developmental Biology, Stem Cells & Aging
Gene Expression, Cell Cycle & Chromosome Biology
Genetics, Genomics & Evolution
<p> Aging, Biochemistry, Cell Biology, Genetics, Genomics, Molecular Biology, Molecular Genetics</p>

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