Dr. Jon Boyle

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.
Boyle

Virulence and Host Range in Intracellular Pathogens

Assistant Professor

Dr. Boyle received his Ph.D. in 2003 with Timothy Yoshino at the University of Wisconsin, Madison, performed his postdoctoral studies with John Boothroyd at Stanford University, and joined the Department in 2008.

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

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Jon Boyle

A fundamental question in the study of pathogenic microorganisms is how host specificity and virulence are determined on a molecular level. My research focuses on addressing these questions using the human pathogen Toxoplasma gondii as a model system. Toxoplasma is an obligate intracellular parasite that is closely related to other pathogens with a significant impact on human health, including the causative agents of malaria and cryptosporidiosis. However, a number of intrinsic features of T. gondii differentiate it from these other organisms, making it a particularly robust system in which to study the evolution of parasitism. Toxoplasma has an extremely broad host range, being capable of infecting all mammalian and bird species.

These unique features of Toxoplasma bring up a number of important questions

What evolutionary events produced a parasite species with such a broad host range?
How has Toxoplasma become such a globally ubiquitous parasite?
Why do different Toxoplasma strains have different levels of virulence and/or compatibility in different hosts?

We can now begin to directly address these questions based the recent identification of parasite effector proteins that determine virulence in the mouse model. One such protein, ROP18, is a secreted kinase that can transform a benign Toxoplasma strain into a lethal one. Understanding the mechanism of action of ROP18, as well as other key parasite effectors, should yield new insights into the evolution of the host-pathogen relationship on the molecular level, and provide a basis for the development of more effective treatment regimens in human cases of toxoplasmosis.

Mechanism of action of ROP18

Fig. 1. Anti-HA immunofluorescence showing the location of HA-tagged ROP18II in host cells 15 minutes post-invasion. Punctate staining (arrowheads) within the host cell is similar to that of other rhoptry proteins (ROP2/3/4).

Expression of a "virulent" allele of ROP18 in a non-virulent Toxoplasma strain dramatically increases the severity of disease. While we know that ROP18 is a protein kinase, and is secreted into the host cell upon invasion (Fig. 1), how it alters virulence is unknown. We study the mechanism of action of ROP18 using a variety of techniques. We use microarrays to identify cellular signaling networks activated or suppressed by ROP18 in different cell types. We use chemical genetics to develop inhibitors that selectively inhibit the action of this kinase. We are also very interested in identifying the physiological substrates of ROP18 (whether host- or parasite-derived), especially those that are relevant to its effect on virulence.

Other effectors

We know from a number of genetic studies that ROP18 is not the only key effector protein in Toxoplasma. We use forward genetics to identify other parasite proteins that play a key role in the host-pathogen interaction, and then attempt to understand their mechanism of action.

In summary, elucidating the cellular and molecular events driven by ROP18 and other parasite effectors is an important step towards determining the molecular mechanisms of Toxoplasma pathogenesis, and has potential to result in the development of new anti-Toxoplasma drugs and treatment regimens. Moreover, the effector proteins that will be identified and characterized are excellent candidates for being involved in driving the incredibly unique population biology and host range of this highly ubiquitous eukaryotic pathogen.

Publication Archive
22 Citations
21 Abstracts
3 PDFs

Recent Publications of Jon Boyle

Bontell, I.L., N. Hall, K.E. Ashelford, J.P. Dubey, J.P. Boyle, J. Lindh, and J.E. Smith (2009) Whole genome sequencing of a natural recombinant Toxoplasma gondii strain reveals chromosome sorting and local allelic variants. Genome Biol 10:RR53

Boyle, J.P., and J.R. Radke (2009) A history of studies that examine the interactions of Toxoplasma with its host cell: emphasis on in vitro models. Int J Parasitol 39:903-914

Boyle, J.P., J.P. Saeij, S.Y. Harada, J.W. Ajioka, and J.C. Boothroyd (2008) Expression quantitative trait locus mapping of Toxoplasma genes reveals multiple mechanisms for strain-specific differences in gene expression. Eukaryot. Cell 7:1403-1414 (PDF Reprint: 571 kb)

Saeij, J.P., S. Coller, J.P. Boyle, M.E. Jerome, M.W. White, and J.C. Boothroyd (2007) Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445:324-327

Boyle, J.P., J.P. Saeij, and J.C. Boothroyd (2007) Toxoplasma gondii: inconsistent dissemination patterns following oral infection in mice. Exp. Parasitol. 116:302-305

Boyle, J.P., J.P. Saeij, M.D. Cleary, and J.C. Boothroyd (2006) Analysis of gene expression during development: lessons from the Apicomplexa. Microbes Infect. 8:1623-1630 (PDF Reprint: 310 kb)

Boyle, J.P., B. Rajasekar, J.P. Saeij, J.W. Ajioka, M. Berriman, I. Paulsen, D.S. Roos, L.D. Sibley, M.W. White, and J.C. Boothroyd (2006) Just one cross appears capable of dramatically altering the population biology of a eukaryotic pathogen like Toxoplasma gondii. Proc. Natl. Acad. Sci., USA 103:10514-10519 (PDF Reprint: 930 kb)

Saeij, J.P., J.P. Boyle, S. Coller, S. Taylor, L.D. Sibley, E.T. Brooke-Powell, J.W. Ajioka, and J.C. Boothroyd (2006) Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314:1780-1783

Hillyer, J.F., S.L. Schmidt, J.F. Fuchs, J.P. Boyle, and B.M. Christensen (2005) Age-associated mortality in immune challenged mosquitoes (Aedes aegypti) correlates with a decrease in haemocyte numbers. Cell Microbiol. 7:39-51

Khan, A., S. Taylor, C. Su, A.J. Mackey, J. Boyle, R. Cole, D. Glover, K. Tang, I.T. Paulsen, M. Berriman, J.C. Boothroyd, E.R. Pfefferkorn, J.P. Dubey, J.W. Ajioka, D.S. Roos, J.C. Wootton, and L.D. Sibley (2005) Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii. Nucleic Acids Res. 33:2980-2992

Boyle, J.P., and T.P. Yoshino (2005) Serotonin-induced muscular activity in Schistosoma mansoni larval stages: importance of 5-HT transport and role in daughter sporocyst production. J Parasitol 91:542-550

Saeij, J.P., J.P. Boyle, M.E. Grigg, G. Arrizabalaga, and J.C. Boothroyd (2005) Bioluminescence imaging of Toxoplasma gondii infection in living mice reveals dramatic differences between strains. Infect. Immun. 73:695-702

Saeij, J.P., J.P. Boyle, and J.C. Boothroyd (2005) Differences among the three major strains of Toxoplasma gondii and their specific interactions with the infected host. Trends. Parasitol. 21:476-481

Bartholomay, L.C., W.L. Cho, T.A. Rocheleau, J.P. Boyle, E.T. Beck, J.F. Fuchs, P. Liss, M. Rusch, K.M. Butler, R.C. Wu, S.P. Lin, H.Y. Kuo, I.Y. Tsao, C.Y. Huang, T.T. Liu, K.J. Hsiao, S.F. Tsai, U.C. Yang, A.J. Nappi, N.T. Perna, C.C. Chen, and B.M. Christensen (2004) Description of the transcriptomes of immune response-activated hemocytes from the mosquito vectors Aedes aegypti and Armigeres subalbatus. Infect. Immun. 72:4114-4126

Vermeire, J.J., J.P. Boyle, and T.P. Yoshino (2004) Differential gene expression and the effects of Biomphalaria glabrata embryonic (Bge) cell factors during larval Schistosoma mansoni development. Mol. Biochem. Parasitol. 135:153-157

How to Contact Jon Boyle

US Mail
University of Pittsburgh
Department of Biological Sciences
102A Life Sciences Annex
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-5842
Lab : (412) 624-5842
FAX : (412) 624-4759
Email : boylej@pitt.edu
Web :

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