Biochemistry
R. Bentley
J. Brodsky
J. Franzen
P. Grabowski
J. Hempel
L. Jen-Jacobson
K. Kiselyov
C. Peebles
J. Rosenberg
A. Schwacha

Cell Biology
J. Brodsky
A. Chung
J. Hildebrand
L. Jacobson
N. Kaufmann
K. Kiselyov
J. Pipas
M.-T. Sáens-Robles
W. Saunders
C. Walsh

Computational Biology
M. Grabe
J. Lawrence
J. Rosenberg

Developmental Biology
G. Campbell
D. Chapman
J. Hildebrand
B. Roman
S. Shostak
B. Stronach
V. Twombly

Ecology
T.-L. Ashman
W. Carson
W. Coffman
S. Kalisz
T. Katzner
R. Relyea
S. Tonsor
B. Traw

Evolution
T.-L. Ashman
A. Bledsoe
S. Kalisz
J. Lawrence
Z.-X. Luo
R. Relyea
S. Shostak
S. Tonsor
B. Traw

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

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

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

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Graham Hatfull

Mycobacterium tuberculosis kills more people than any other single infectious agent. Since antibiotics are available and the BCG vaccine is in widespread use, why do nearly three million people die each year from TB? The answer, in part, is that we really don't understand this curious bacterium or what parts of its genetic instructions make this such a deadly pathogen.

At the heart of our strategies to understand mycobacterial genetics is the mycobacteriophages - viruses that infect the mycobacteria (an electronmicrograph of bacteriophage Bxz1 is shown to the left). These are easy to grow and manipulate and offer advantages over working with the slow-growing mycobacteria (such as M. tuberculosis) that can take up to a month to produce a colony on an agar plate. Phages are also rich sources of a wide variety of potential genetic and molecular tools that can be used to study - and to modify - their bacterial hosts.

Here's just a flavor of some of the current studies going on in the lab (to the right we see Nick Pannunzio extracting Serratia phage OT8M from a cesium gradient; if you look at the picture you can see how big it is...):

• Bacteriophage genomics. We have sequenced about half-a-dozen mycobacteriophage genomes and - in collaboration with Dr. Hendrix - an equivalent number of other phage genomes. These studies have not only provided some valuable insights into how this incredible collection of organisms have evolved, but fuels our mycobacterial investigations by continually providing new phage systems to study.
• Mycobacterial Gene Expression. We have identified novel strategies that the mycobacteria use for regulating gene expression. We have used these for developing tools for controlled expression of genes in mycobacteria and are now delving into the mechanisms of how these system works.
• Site-specific recombination. Several of the mycobacteriophages that we are investigating integrate their DNA into the host chromosome (and can excise them too). We are building a variety of mycobacterial vectors that use these systems to permit the integration of any desirable genes into mycobacterial genomes. We are also using these as model systems to investigate the molecular mechanisms involved in site-specific recombination and attempting to elucidate how phages dictate the directionality of these events.
• Tools - Genetic and Clinical. Studying the mycobacteria and their phages has great potential for the development of novel tools for their genetics but also for a more direct clinical involvement. Two systems we have been involved in developing are multivalent recombinant BCG vaccines and Luciferase Reporter Phages, but there are numerous additional strategies awaiting further development!

Publication Archive
96 Citations
88 Abstracts
71 PDFs

Recent Publications of Graham Hatfull

Morris, P., L.J. Marinelli, D. Jacobs-Sera, R.W. Hendrix, and G.F. Hatfull (2008) Genomic characterization of mycobacteriophage Giles: evidence for phage acquisition of host DNA by illegitimate recombination. J. Bacteriol. 190:2172-2182 (PDF Reprint: 908 kb)

van Kessel, J.C., and G.F. Hatfull (2008) Efficient point mutagenesis in mycobacteria using single-stranded DNA recombineering: characterization of antimycobacterial drug targets. Mol. Microbiol. 67:1094-1107

Ghosh, P., L.A. Bibb, and G.F. Hatfull (2008) Two-step site selection for serine-integrase-mediated excision: DNA-directed integrase conformation and central dinucleotide proofreading. Proc. Natl. acad. Sci., USA 105:3238-3243

van Kessel, J.C., and G.F. Hatfull (2008) Mycobacterial recombineering. Methods. Mol. Biol. 435:203-215

Ojha, A.K., A.D. Baughn, D. Sambandan, T. Hsu, X. Trivelli, Y. Guerardel, A. Alahari, L. Kremer, W.R. .J.r. Jacobs, and G.F. Hatfull (2008) Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria. Mol. Microbiol. 69:164-174

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

Ojha, A., and G.F. Hatfull (2007) The role of iron in Mycobacterium smegmatis biofilm formation: the exochelin siderophore is essential in limiting iron conditions for biofilm formation but not for planktonic growth. Mol. Microbiol. 66:468-483

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

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

van Kessel, J.C., and G.F. Hatfull (2006) Recombineering in Mycobacterium tuberculosis. Nat. Methods :In Press

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)

Ghosh, P., L.R. Wasil, and G.F. Hatfull (2006) Control of phage bxb1 excision by a novel recombination directionality factor. PLoS Biol. 4:e186 (PDF Reprint: 3.4 MB)

Hendrix, R.W., M.C.M. Smith, R.N. Burns, M.E. Ford, and G.F. Hatfull (1999) Evolutionary relationships among diverse bacteriophages and prophages: All the World's a Phage. Proc. Natl. Acad. Sci., USA 96:2192-2197 (PDF Reprint: 744 kb)

How to Contact Graham Hatfull

 
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