Research Interests The Hendrix lab is investigating how proteins work, and in particular how proteins interact with each other to assemble into an ordered biological structure. We use bacteriophages as experimental subjects because these viruses provide a system that is almost unequaled in the ease with which we can apply a wide array of experimental approaches (molecular genetics, biochemistry, biophysics, electron microscopy, structural biology) to tackle sophisticated questions about how proteins interact during assembly. An important advance in our understanding of virus assembly that has come out of recent studies is that viral proteins go through a complex series of transitions (covalent and conformational changes) as assembly proceeds. In this view of assembly, finding their correct place in the growing structure is only the first step for the protein subunits: once they are in place they must flex, wiggle, and adjust their contacts with neighbors to progressively strengthen or otherwise modulate the properties of the structure as a whole. As we learn more, virus assembly comes increasingly to resemble an elaborately choreographed organic ballet. Our lab is studying virus assembly by studying individual examples of transitions in protein structure that take place during assembly of bacteriophages; we are also working to understand how these individual steps fit together in the overall logic of the assembly ballet. The principles we are learning describing how proteins interact to build a biological structure are applicable to many other biological systems in addition to viruses--from protein complexes that regulate gene expression to cytoskeletons--including those for which direct experimentation to address these questions is prohibitively difficult. Head assembly of bacteriophage HK97. HK97 is a close relative of the well known bacteriophage lambda with a particularly informative head assembly pathway. We are studying the structures of the various capsid precursors on this pathway by cryo-electron microscopy and X-ray crystallography. We can carry out most of the steps in the pathway in vitro, allowing us to study the detailed biochemical and biophysical properties of each reaction (including an unusual autocatalytic covalent crosslinking of all the head subunits). We have determined the DNA sequence of the 40 KB phage genome, which makes it easy to design and construct mutants that allow detailed dissection of each step of the pathway. Protein engineering in phage lambda tail fibers. The long tail fibers of phage lambda, which we discovered recently, reveal unexpected examples of novel protein structure. We are studying them to understand these new aspects of protein structure and also because of the possibility of developing new kinds of cloning and protein fusion vectors based on the novel properties of the fibers. The Bacteriophage Genome Project. In collaboration with Graham Hatfull and other members of the Pittsburgh Bacteriophage Institute, we have begun a project to determine the genomic sequences of a few dozen bacteriophages. We are comparing the sequences we produce to each other and to sequences in the databases in order to learn about mechanisms of virus evolution and the genetic structures of phage populations. The sequences of head and tail fiber genes of new phages are also of direct relevance to our studies of these aspects of HK97 and lambda biology.   Selected Publications Lin F, Lim D, Wixson RL, Milos S, Hendrix RW, Makhsous M. Validation of a computer navigation system and a CT method for determination of the orientation of implanted acetabular cup in total hip arthroplasty: A cadaver study. Clin Biomech (Bristol, Avon). 2008 Jun 7. Morris P, Marinelli LJ, Jacobs-Sera D, Hendrix RW, Hatfull GF. Genomic characterization of mycobacteriophage giles: evidence for phage acquisition of host DNA by illegitimate recombination. J Bacteriol. 2008 Mar;190(6):2172-82. Lim D, Lin F, Hendrix RW, Moran B, Fasanati C, Makhsous M. Evaluation of a new sitting concept designed for prevention of pressure ulcer on the buttock using finite element analysis. Med Biol Eng Comput. 2007 Nov;45(11):1079-84. Pham TT, Jacobs-Sera D, Pedulla ML, Hendrix RW, Hatfull GF. Comparative genomic analysis of mycobacteriophage Tweety: evolutionary insights and construction of compatible site-specific integration vectors for mycobacteria. Microbiology. 2007 Aug;153(Pt 8):2711-23. Weigele PR, Pope WH, Pedulla ML, Houtz JM, Smith AL, Conway JF, King J, Hatfull GF, Lawrence JG, Hendrix RW. Genomic and structural analysis of Syn9, a cyanophage infecting marine Prochlorococcus and Synechococcus. Environ Microbiol. 2007 Jul;9(7):1675-95. Complete Publication Listing     Other Links Biological Sciences University of Pittsburgh

Roger W Hendrix, Ph.D. Office:  A340A Langley Hall Lab:A340A Langley Hall Phone:(412) 624-4674 Fax: (412) 624-4870 rhx+@pitt.edu     Education 1965 B.S. Biology California Institute of Technology 1970 Ph.D. Biochemistry & Molecular Biology Harvard University 1971 - 1973 Postdoc Biochemistry Standford University   Lab Personnel Postdoctoral Fellows: Dr. Welkin Pope Graduate Students: Xiaoxian Dai, Lin Hao, Jianfei Hua, Dan-Ju Tso Staff: Robert Edgar, Brian Firek, Ching-Chung Ko