The Varani research group study how proteins and nucleic acids interact with each other. The aim of the group is to understand at the physical chemical level how proteins bind nucleic acids and to exploit this knowledge to design new proteins and synthesize small molecule drugs that control human regulatory networks or repress viral replication. Members of the group use spectroscopic (NMR), crystallographic, computational and biochemical techniques. The group is also investigating the three-dimensional structure of telomerase, an enzyme composed of both RNA and protein components responsible for maintenance of the physical ends of chromosomes. Telomerase is a new target for anticancer therapy because it is selectively activated in >90% of all human cancers.
The fundamental goal of the research group is to design proteins with new activities and synthesize new drugs to treat infectious and chronic disease. If we harness this knowledge, we would ultimately be able to rationally design new proteins and synthesize small molecule drugs that control gene expression networks. New designer proteins would provide ideal reagents to dissect gene expression pathways, while small molecule drugs that interfere with nucleic acid metabolism would be of tremendous value in the treatment of infectious disease.
New experimental and computational tools are being developed. By exploiting new NMR methods, and by interfacing closely with computational biology and theoretical chemistry (sequence analysis, homology modeling, structure-based drug design), the Varani group aims to determine structures of increasing complexity and to measure new experimental properties of biological interfaces. The goal is to develop predictive tools capable of describing the energetic and dynamic properties of such interfaces, so that the task of designing new interactions could be achieved successfully.
A wide range of experimental and computational techniques are applied. Students and post-doctoral fellows in the group use NMR spectroscopy, X-ray crystallography, computational biology and biochemical techniques: often all of these tools are used by a single student to tackle a specific problem.
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Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research