Analysis of the cellular function of type III secr.. (CHLTRT3SE)
Analysis of the cellular function of type III secretion effectors of Chlamydia trachomatis
Start date: 01 Jan 2009,
End date: 31 Dec 2011
"Chlamydiales are a large group of highly related obligate intracellular bacteria that includes the human pathogens Chlamydia trachomatis and Chlamydophila pneumoniae. C. trachomatis is an agent of genital and ocular infections, and Cph. pneumoniae causes atypical pneumonias. All Chlamydiae use a type III secretion (T3S) apparatus to translocate ~ 60-90 effector proteins into host cells. These effectors are thought to play crucial roles in chlamydial dissemination but little is known about their functions because Chlamydiae are intractable to genetic manipulation. I aim to identify new C. trachomatis T3S effectors and to further understand the secretion and function of known effectors. I will explore the ability of T3S systems to recognise substrates from heterologous systems and use Yersinia and Salmonella to: screen for T3S signals in potential effectors of C. trachomatis; examine the function and expression of a few uncharacterised C. trachomatis T3S effectors, by conducting yeast two-hybrid screens and producing specific polyclonal antibodies; establish a “proof-of-principle” for the long-term goal of using a Salmonella T3S effector poly-mutant strain capable of translocating chlamydial T3S effectors into host cells. This will be done by using Yersinia to determine the requirements for T3S of full-length C. trachomatis Inc proteins, which localise to the vacuole enclosing intracellular bacteria, and by using Salmonella effector poly-mutant strains to study the biological function of the chlamydial effector Tarp. This promises important advances in our understanding of the virulence of intracellular pathogens, ultimately helping to combat infectious diseases. The execution of this work will therefore have an impact on European health research and will help me to establish an independent research position upon return to my home country, Portugal, after benefiting from an Intra-European Marie Curie Fellowship."
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