Athens, Ga. – When people don’t communicate effectively, relationships suffer and entire organizations can fail. When cells don’t communicate effectively, disease and sometimes death follows.
A University of Georgia researcher, with a grant from the National Science Foundation, is tracing the origins of a protein family that plays a key role in communicating environmental signals in the cell. Natarajan Kannan, a Georgia Cancer Coalition Distinguished Scholar, will use $969,822 provided by the NSF CAREER Award program over the next five years to gain an in-depth understanding of the evolution of kinases, a protein that controls cellular signaling pathways. The results could help researchers develop new strategies for treating a variety of diseases.
“Kinases are involved in a multitude of diseases, including cancer and Alzheimer’s,” said Kannan, an assistant professor of biochemistry and molecular biology in the Franklin College of Arts and Sciences and a member of the UGA Institute of Bioinformatics. “A deeper understanding of the evolutionary design principles will provide new avenues for targeting these proteins in disease states.”
Most diseases involve some breakdown in cell communication. Cells affected by cancer do not respond to regulatory signals and replicate uncontrollably. Alzheimer’s disease disrupts nerve signal transmissions at particular synapses, which are junctions between nerve cells.
Kannan will measure the similarities and differences between kinases in eukaryotes-complex cells that contain membrane-bound structures such as nuclei and mitochondria-and prokaryotes-simpler cells that lack internal membrane-bound structures and are believed to be precursors of eukaryotes. After identifying the protein sequence similarities and differences between various kinases as well as comparing their crystal structures and functional data, Kannan will create testable models of protein kinase evolution and regulation. The models will help researchers identify molecular structural features shared by different classes of kinases-some involved in diseases such as cancer and malaria-and relate them to differences in activities.
“Kinases are critical proteins that are involved in many aspects of biology,” said Jessica Kissinger, director of the UGA Institute of Bioinformatics. “Many kinases have evolved to be unique to a parasite lineage or cancer activity and thus represent putative drug targets. Professor Kannan is expertly qualified to both identify and understand the specific adaptations to members of this protein family and explore their utility as therapeutic targets.”
In collaboration with Krzysztof Kochut, a professor of computer science in the Franklin College, Kannan will also develop an ontology-an overall framework of common terms-to aid researchers in identifying and studying relationships among different groups of kinases.
“Currently, information on protein kinases is stored in disparate sources and data formats with wide variations in terminology for the same functions, posing major challenges for researchers,” Kannan said. “The proposed ontology will help overcome this challenge by conceptualizing protein kinase knowledge in one place.”
With Erin Dolan, UGA associate professor of biochemistry and molecular biology and senior scholar in biology education, Kannan will also use the protein kinase ontology in the classroom and later evaluate it for its effectiveness in helping students understand evolutionary and integrative concepts in biology. The CAREER Award funding enables Kannan to introduce undergraduates and high school students, particularly under-represented minorities, to hands-on research. Students will be recruited through the Center for Undergraduate Research Opportunities, Young Dawgs and the NSF-funded fungal genomics and computational biology program.
“The integrated research and educational plan developed by Dr. Kannan provides a platform for exciting scientific discovery and an innovative instructional model with applications at multiple levels, in diverse disciplines,” said Stephen Hajduk, a professor and head of the UGA department of biochemistry and molecular biology.
The NSF CAREER Award is among the most competitive awards available from the National Science Foundation. In 2011, only 15 percent of all proposals submitted to the NSF’s Directorate for Biological Sciences, which oversees Kannan’s project, were funded.