The Dudley laboratory uses systems biology approaches to elucidate two core components of complex genetic systems: gene function and regulation.
Systems Genetics
Individuals in a population display a wide variety of health-related traits, such as susceptibility to a given disease or response to a specific therapy. Many of these traits or "phenotypes" have a significant genetic component, i.e. phenotypic differences between individuals can be explained by their DNA sequence or "genotype". The size of the human genome (3 billion base pairs) and the large number of differences between individuals (an estimated 12 million) presents a major challenge to identifying the changes or "polymorphisms" responsible for a trait. These efforts are further hampered by the fact that genes interact in complex ways, such that various combinations of polymorphisms can produce a wide array of phenotypes.
In the next 5 to 10 years, advances in DNA sequencing technology will deliver low cost personal genome sequencing, commonly referred to as the $1000 human genome. This tipping point brings decoding an individual´s DNA sequence within the cost range of common medical procedures. The technology will generate huge quantities of data, but it has vastly outpaced methods for understanding the functional consequences of genetic polymorphisms and their interactions. The Dudley lab is using yeast to develop new methods that will surmount these technical and conceptual limitations.
Technology Development
The Dudley group develops a wide array of experimental and computational methods to achieve the ultimate goal of accurately and comprehensively modeling the behavior of a cell. This is an ambitious goal, and their work involves collaborations between experts across many scientific disciplines (biology, engineering, mathematics, chemistry, and physics). Because biological processes are highly dynamic, the lab is developing microfluidic methods for measuring cellular response to large numbers of environmental perturbations. Because spatial context is crucial for biological processes, the lab is developing automated imaging and biochemical methods for studying protein and RNA localization. Because genotype plays an important role in an individual´s ability to respond to environmental and developmental cues, the lab is developing methods to identify the genetic perturbations responsible for a trait. And, because the ultimate test of computational models is their ability to predict an organism´s response to novel perturbations, the lab is developing synthetic biology methods to enable rapid re-engineering of genetic networks and test their capacity for new biological functions.
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