HOST-SELECT · Functional Analysis of Host Genetic Variants: Biomarker Selection Towards Improving Female Subfertility Diagnosis and Treatment
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-07-01 → 2019-06-30
- EU contribution
- €159,461
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Functional Analysis of Host Genetic Variants: Biomarker Selection Towards Improving Female Subfertility Diagnosis and Treatment
The main purpose of this proposal was to test the role of individual genetic make-up in human tubal pathologies caused by a genital infection with Chlamydia trachomatis (CT). CT is the most common bacterial sexually transmitted infection, with more than 100 million new infections each year. Studies show that tubal infection with CT may lead to serious pathological complications, such as infertility and ectopic pregnancy. Fertility issues affect roughly 15% of couples attempting to conceive, hence they represent a significant public health concern. The prevalence of fertility issues is expected to increase, partly due to the rising rates of CT infections. Researchers have shown that, following a genital CT infection, women carrying particular gene variants (single nucleotide polymorphisms; SNPs) have a higher risk of developing these complications, compared to those women that have not inherited these variants. How these differences in risk are driven by SNPs is not sufficiently understood. Identifying key genetic factors in tubal pathologies and understanding how they contribute to these conditions would potentially advance screening and therapy of individuals suffering from these issues. We have therefore a) set out to determine which key genes and their variants play a role in CT-caused tubal pathology and b) tested the effect of these variants in a 3D organoid model of a human Fallopian tube – currently the most advanced research model for tubal infection. As a personal goal, an additional purpose of the proposal was to obtain specific skills and expertise in techniques, among others cultivation of tubal 3D organoids from cells obtained from patients, their application in SNP studies of CT infection and genetic manipulation in these organoids.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENCoordinatorGermany
Links
Data: CORDIS, © European Union