Thursday, November 21, 2024
11/21/2024
One of the manifestations of Chlamydial pathogenesis in women is tubal factor infertility (TFI). The molecular mechanism underpinning the pathologic changes that cause TFI is poorly understood. We have reported that the time of day of infection influences chlamydia infectivity and pathogenesis. Results from our lab show that when circadian rhythms were disrupted using a Jet lag model, chlamydia-infected mice had increased infectivity and pathology. Our work has demonstrated that miRNAs and genes associated with circadian rhythms are differentially expressed during chlamydia infection. Our premise in this study hypothesizes that circadian rhythms have a role in controlling/regulating chlamydial pathogenesis, leading to infertility. The central goal of this project is to understand the role of circadian rhythms on chlamydial pathogenesis through these aims (1) Investigate the association of host circadian rhythms with chlamydial pathogenesis. We hypothesize that circadian control of chlamydial pathogenesis is essential in determining disease outcomes. We will determine the role and involvement of clock genes Bmal1, Per2, and Cry1 on chlamydial pathogenesis using commercially available Bmal1KO, Per2KO, and Cry1KO mice. (2) Define the circadian control of pathways involved in chlamydial pathogenesis. We hypothesize that the intrinsic disposition of the genital tract to pathogeneic changes will depend on what genes/proteins are activated or inhibited by clock genes. We will also determine genes that are undergoing cycling at different states of chlamydia infection. We will test this hypothesis using C. muridarum infected WT, Bmal1KO, Per2KO, and Cry1KO mice. This study gives us a basis to predict the level of severity of pathogenesis after chlamydia infection and identify new underlying mechanisms involved in chlamydia pathogenesis. By accomplishing the outcomes of the specific aims, we predict that the knowledge gained will positively impact women's reproductive health.
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