About Dr. Travis Jewett
The sexually transmitted bacterium Chlamydia trachomatis causes substantial morbidity in the US and world wide. Our research efforts are focused on understanding the virulence factors employed by Chlamydiae to cause disease.
The Tarp effector:
A C. trachomatis effector called Tarp, for translocated actin recruiting protein is a candidate virulence factor. Tarp is tyrosine phosphorylated by a host cell kinase and is associated with actin recruitment during Chlamydiae entry. Tarp protein domains have been identified and include: i) an actin binding and nucleating domain, ii) a proline rich oligomerization domain and iii) a phosphorylation domain. How these protein domains function during and after bacterial entry is the primary focus of our laboratory.The actin binding domain:
The Tarp orthologs harbor between 1 to 4 actin binding domains (ABDs). Recent studies suggest that different Tarp proteins have the capacity to nucleate actin filaments by alternative nucleation mechanisms. Ongoing projects in our lab are concentrated on comparing the ability of different Tarps to polymerize actin.The phosphorylation domain:
The function of the Tarp phosphorylation domain remains largely unknown. Src-homology domain 2 (SH2) containing proteins are candidate Tarp interacting proteins and recently, PI3 kinase was implicated in association with phosphorylated Tarp. Modification of lipids by PI3K ultimately regulates a variety of cellular processes. We predict that Tarp recruitment of PI3K plays a vital role in the establishment of chlamydial infection. Projects are currently underway to examine the host cell signaling cascades activated following Tarp phosphorylation and the possible contribution these pathways have in establishing chlamydial infections.
- Jiwani S, Ohr RJ, Fisher ER, Hackstadt T, Alvarado S, Romero A, Jewett TJ. Chlamydia trachomatis Tarp cooperates with the Arp2/3 complex to increase the rate of actin polymerization. Biochem Biophys Res Commun. 2012 Apr 20;420(4):816-21. Epub 2012 March 23.
- Jewett TJ, Miller NJ, Dooley CA, Hackstadt T. The conserved Tarp actin binding domain is important for chlamydial invasion. PLoS Pathog. 2010 Jul 15;6(7):e1000997.
- Lutter EI, Bonner C, Holland MJ, Suchland RJ, Stamm WE, Jewett TJ, McClarty G, Hackstadt T. Phylogenetic Analysis of Chlamydia trachomatis Tarp and Correlation with Clinical Phenotype. Infect Immun. 2010 Sep;78(9):3678-88. Epub 2010 Jul 6.