HOST-SELECTProject ID: 752999
Functional Analysis of Host Genetic Variants: Biomarker Selection Towards Improving Female Subfertility Diagnosis and Treatment
Roughly 15% of couples trying to conceive suffer from subfertility. One of its leading causes is developed pathology in woman’s fallopian tubes (tubal pathology or TP). Persistent infection with Chlamydia trachomatis (CT) is the single most common cause of TP. Women with a certain genetic makeup are more likely to develop TP after CT infection. I have so far identified 8 host genes and 13 genetic variants associated with CT infection and TP. Their exact function is, however, not yet elucidated. In this project, I will research the effect of found host genetic factors on CT infection and TP, by analysing their function in a human fallopian tube organoid model. This model optimally simulates in vivo conditions in the tubes. The host institution offers the technology and expertise for conducting such research.
The analysis will be achieved via RNA interference gene-silencing technology, successfully applied by the host group in their CT research for years. I will then introduce targeted mutations via CRISPR/Cas9 gene-editing assay and study the effect on the course of the infection. Lastly, I will determine the network of involved gene pathways in order to explain the underlying pathogenesis.
This will be the first ever functional analysis of host factors associated with CT infection and TP in an organoid. The analyses will require learning and applying cutting-edge techniques (RNA interference and CRISPR/Cas9). Also, it will be the first delivery of specific, targeted mutations into a CT-infected organoid and first such study of their effect on developing pathologies.
Achieving these objectives will facilitate the development of a novel diagnostic assay in order to address an existing health need - improving the currently suboptimal diagnosis of women at risk of CT-associated TP and reducing referrals to invasive, burdening and costly surgical examinations. I have also developed a detailed plan for disseminating the findings to experts and general public.
EU contribution: EUR 159 460,80