Friday, March 24, 2017 at 11:15am
A. Keith Dunker
Center for Computational Biology and Bioinformatics
Department of Biochemistry and Molecular Biology
Indiana University Schools of Medicine and Informatics
After receiving his B.S. in Chemistry from UC Berkeley in 1965, Dr. Dunker attended the University of Wisconsin at Madison where he earned his M.S. in Physics and his Ph.D. in Biophysics under the direction of Dr. Roland Rueckert. From 1969-1973, he carried out postdoctoral research at Yale University in the laboratory of Donald Marvin where he worked on the structure and cell penetration of the filamentous phage fd. Dr. Dunker started research in computational biology and bioinformatics in the mid-1980s and began using bioinformatics to study intrinsically disordered roteins in the mid-1990s, where he and his collaborators were the first to consider these proteins as a distinct class with important biological functions. His bioinformatics research goals over the next several years include the improvement of intrinsic disorder predictions, especially with respect to identifying different types of disorder (flavors) and then to understanding the relationships between the different types of disorder and protein function, i.e., to understand flavor-function relationships. In addition, he wants to combine bioinformatics prediction with laboratory experimentation to develop new approaches for understanding protein-protein and protein-nucleic acid signaling interactions that involve intrinsically disordered proteins. Ongoing work suggests that the original proteins on earth were intrincically disordered and that protein evolution followed a disorder to order pathway. Laboratory experiements to test the disorder to order pathway for protein evolution will be getting underway.
Abstract: Key developmental and regulatory proteins use intrinsically disordered protein (IDP) regions to carry out crucial functions, typically to bind to and regulate their own active sites via auto-inhibitory domains or to modulate the functions of their DNA, RNA and/or protein partners. For all of the developmental and regulatory proteins examined so far, these intra- and/or intermolecular interactions are altered or modulated by both alternative splicing (AS) and by post-translational modification (PTM), both of which map to the IDP regions. During development, both AS and PTMs in IDP regions have been shown to be tissue-specific. Thus, both AS and PTMs “rewire” protein-protein and gene-regulatory networks and pathways in a tissue-specific manner. Given these observations, we propose that IDP, AS, and PTM working in concert provide a toolkit that underlies (enables?) both the evolution of multicellular organisms and the developmental biology of individual multicellular organisms