Chlamydia trachomatis is a leading cause of sexually transmitted disease - with reported prevalence rates of up to 17% among asymptomatic women in Europe - and as such a frequent cause of infertility. While these bacteria have been known for more than a decade to protect infected cells from apoptosis, the lack of tools for genetic manipulation of chlamydiae significantly hampered the investigation of underlying molecular mechanisms and their role during infection. Yet, the research group of Dr. Valdivia (outgoing host) has recently established a unique system to perform forward genetics in chlamydiae, and in course of the proposed project Dr. Sixt (the fellow candidate) will be among the first researchers able to learn and exploit these techniques. In this process, she will first recover mutant C. trachomatis strains that display a reduced potential to block apoptosis. This will subsequently enable her to identify bacterial anti-apoptotic factors and to study the significance of Chlamydia-mediated cell death modulation in a murine infection model. Finally, she will assess the effect of interference with the anti-apoptotic trait on the immunogenic potential of dying host cells, based on the detection of specific cellular “immunogenicity predictors” that were recently identified by the group of Dr. Kroemer (European return host). This multidisciplinary investigation will provide invaluable insights into chlamydial virulence and will help to predict whether the anti-apoptotic trait may be a potential new drug target. The project offers Dr. Sixt extensive training that is highly complementary to her previous research experiences. The acquired skills, international experience, and newly established contacts will place her in an excellent position to take a leading role in the further development of this scientific field and will enable her to implement infection biology at the European return host institute, which will further expand the institute’s areas of excellence.
Fields of science
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