Dr. Roger Hendrix

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
J. Boyle
G. Hatfull
R. Hendrix
J. Lawrence
J. Pipas
M. Popa
R.L. Duda
S. Godfrey
V. Oke

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Hendrix

Mechanisms of Assembly and Principles of Structure in Bacterial Viruses

Professor

Dr. Hendrix received his Ph.D. in 1970 with James Watson at Harvard University, performed his postdoctoral studies with Dale Kaiser at Stanford University, and joined the Department in 1973.

Currently, Dr. Hendrix is accepting graduate students in his laboratory. Dr. Hendrix is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Roger Hendrix

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.

A portion of the high resolution structure of the bacteriophage HK97 capsid, determined by x-ray crystallography (see the paper by Wikoff et al.). The picture shows an area of the structure around one of the 3-fold symmetry axes; it includes portions of 9 different copies of the 420 identical protein subunits that make up the structure. In addition to backbone traces of the subunits, it shows 3 of the 420 inter-subunit covalent bonds (yellow amino acid side chains) that link all the subunits of the capsid into the fabulous chainmail topology. (This picture is a stereo pair; to see it in 3 dimensions, stare through the picture as if looking into the distance until the images from each eye merge in the middle.) The structure determination was carried out by our amazing collaborators Bill Wikoff and Jack Johnson at The Scripps Research Institute.

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.

This small splash pond is located just above the high tide line at the Pittsburgh Bacteriophage Institute Field Station on Vinalhaven Island off the coast of Maine. We have begun to expand our studies of bacteriophage genome sequences to include genome sequences from unselected natural populations. This pond contains approximately 100,000,000 phage particles per milliliter. We are using DNA sequencing and DNA array technologies to compare the genes in this collection of phages with those of domesticated phages and those of other natural phage populations. The Phage Genome Project is a collaboration between our lab and those of Graham Hatfull and Jeffrey Lawrence.

Publication Archive
100 Citations
69 Abstracts
54 PDFs

Recent Publications of Roger Hendrix

Pham, T.T., D. Jacobs-Sera, M.L. Pedulla, R.W. Hendrix, and G.F. Hatfull (2007) Comparative genomic analysis of mycobacteriophage Tweety: evolutionary insights and construction of compatible site-specific integration vectors for mycobacteria. Microbiology 153:2711-2723

Conway, J.F., N. Cheng, P.D. Ross, R.W. Hendrix, R.L. Duda, and A.C. Steven (2007) A thermally induced phase transition in a viral capsid transforms the hexamers, leaving the pentamers unchanged. J. Struct. Biol. 158:224-232

Pope, W.H., P.R. Weigele, J. Chang, M.L. Pedulla, M.E. Ford, J.M. Houtz, W. Jiang, W. Chiu, G.F. Hatfull, R.W. Hendrix, and J. King (2007) Genome sequence, structural proteins, and capsid organization of the cyanophage Syn5: a "horned" bacteriophage of marine synechococcus. J. Mol. Biol. 368:966-981

Weigele, P.R., W.H. Pope, M.L. Pedulla, J.M. Houtz, A.L. Smith, J.F. Conway, J. King, G.F. Hatfull, J.G. Lawrence, and R.W. Hendrix (2007) Genomic and structural analysis of Syn9, a cyanophage infecting marine Prochlorococcus and Synechococcus. Environ. Microbiol. 9:1675-1695

Pham, T.T., D. Jacobs-Sera, M.L. Pedulla, R.W. Hendrix, and G.F. Hatfull (2007) Comparative genomic analysis of mycobacteriophage Tweety: evolutionary insights and construction of compatible site-specific integration vectors for mycobacteria. Microbiology 153:2711-2723

Gan, L., J.A. Speir, J.F. Conway, G. Lander, N. Cheng, B.A. Firek, R.W. Hendrix, R.L. Duda, L. Liljas, and J.E. Johnson (2006) Capsid conformational sampling in HK97 maturation visualized by X-ray crystallography and cryo-EM. Structure 14:1655-1665 (PDF Reprint: 3.0 MB)

Hanauer, D.I., D. Jacobs-Sera, M.L. Pedulla, S.G. Cresawn, R.W. Hendrix, and G.F. Hatfull (2006) Inquiry learning. Teaching scientific inquiry. Science 314:1880-1881

Conway, J.F., N. Cheng, P.D. Ross, R.W. Hendrix, R.L. Duda, and A.C. Steven (2006) A thermally induced phase transition in a viral capsid transforms the hexamers, leaving the pentamers unchanged. J. Struct. Biol. 0:

Ross, P.D., J.F. Conway, N. Cheng, L. Dierkes, B.A. Firek, R.W. Hendrix, A.C. Steven, and R.L. Duda (2006) A free energy cascade with locks drives assembly and maturation of bacteriophage HK97 capsid. J. Mol. Biol. 364:512-525 (PDF Reprint: 1.8 MB)

Hatfull, G.F., M.L. Pedulla, D. Jacobs-Sera, P.M. Cichon, A. Foley, M.E. Ford, R.M. Gonda, J.M. Houtz, A.J. Hryckowian, V.A. Kelchner, S. Namburi, K.V. Pajcini, M.G. Popovich, D.T. Schleicher, B.Z. Simanek, A.L. Smith, G.M. Zdanowicz, V. Kumar, C.L. Peebles, W.R. .J.r. Jacobs, J.G. Lawrence, and R.W. Hendrix (2006) Exploring the mycobacteriophage metaproteome: phage genomics as an educational platform. PLoS Genet. 2:e92 (PDF Reprint: 3.2 MB)

Duda, R.L., R.W. Hendrix, W.M. Huang, and J.F. Conway (2006) Shared architecture of bacteriophage SPO1 and herpesvirus capsids. Curr. Biol. 16:440

Twarock, R., and R.W. Hendrix (2006) Crosslinking in viral capsids via tiling theory. J. Theor. Biol. 240:419-424 (PDF Reprint: 430 kb)

Wikoff, W.R., J.F. Conway, J. Tang, K.K. Lee, L. Gan, N. Cheng, R.L. Duda, R.W. Hendrix, A.C. Steven, and J.E. Johnson (2006) Time-resolved molecular dynamics of bacteriophage HK97 capsid maturation interpreted by electron cryo-microscopy and X-ray crystallography. J. Struct. Biol. 153:300-306 (PDF Reprint: 1.0 MB)

Li, Y., J.F. Conway, N. Cheng, A.C. Steven, R.W. Hendrix, and R.L. Duda (2005) Control of virus assembly: HK97 "Whiffleball" mutant capsids without pentons. J. Mol. Biol. 348:167-182 (PDF Reprint: 1.0 MB)

Lee, K.K., H. Tsuruta, R.W. Hendrix, R.L. Duda, and J.E. Johnson (2005) Cooperative reorganization of a 420 subunit virus capsid. J. Mol. Biol. 352:723-735 (PDF Reprint: 400 kb)

How to Contact Roger Hendrix

US Mail
University of Pittsburgh
Department of Biological Sciences
357A Crawford Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-4674
Lab : (412) 624-4674
FAX : (412) 624-4870
Email : rhx+@pitt.edu
Web :

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