DNA replication is one of the major targets of cancer therapies, as cancer cells tend to proliferate faster than normal cells and are generally more prone to replication stress. Most of our current knowledge about DNA replication initiation, or origin firing, currently comes from model organisms, such as yeast, but their applicability to the human system is limited. It is important to study replication initiation in human cells in order to be able to exploit the findings in cancer therapies. The main objectives of this project are to identify novel players in various stages of human replication initiation and characterize the non-catalytic roles of DNA polymerase epsilon and protein Timeless in replisome assembly.
The research project investigated the effect of different strains of human pathogen Helicobacter pylori (H. pylori) on liver cells. The results of the project demonstrate that pathogenic strains of H. pylori induce the formation of invasive structures (invadosomes) in liver cells dedicated in degrading the surrounding environment. The assembly of rosette-shaped invadosomes is caused by CagA present in the genome of pathogenic H. pylori, resulting in the activation of inflammatory response in liver cells, changes the shape and migration ability of the cells as well as alters the contacts between liver cells. These changes subvert the normal liver cell functions and behaviour leading to liver damages. The results of this study are especially important as they clarify the distinct effect of different strains of H. pylori on liver cells. We are immensely proud to show for the first time the induction of invadosomes by bacterial protein (CagA). In addition, we have demonstrated the direct link between the inflammatory response and invasion of liver cells, knowledge that clarifies the mechanisms behind pathogen-induced liver damages. The results of our study are important for the scientific community as well as for the doctors and society. In Estonia, 70% of the adult population is infected by H. pylori and research shows high prevalence of pathogenic strains among circulating H. pylori. Therefore, it is well justified to carry out dedicated research on this bacterium and to know if, how and which H. pylori strains may affect the development of liver diseases. Our results will help the doctors to understand better the various aspects of H. pylori infection and support the personalized medicine. We are proud to have established an excellent H. pylori research team dedicated in training scientists with high knowledge about H. pylori and ability to work with this complicated pathogen.
Helicobacter pylori (H. pylori) is a human pathogen colonizing the human gastric epithelium in about half of the world´s population leading to peptic ulcer disease, atrophic gastritis and gastric cancer. Pathogenic strains of H. pylori possess several virulence factors, like CagA and VacA, correlating with higher gastric virulence and severely altered signal transduction. Recent studies have demonstrated the effect of H. pylori on gastro-intestinal microbiota leading to the progression of many intestinal as well as extra-intestinal diseases. The main goal of our study is to understand the effect of H. pylori colonization on the composition of the gut microbiota and on the progression of liver diseases. Our study has three specific aims: 1) Characterize the association between gastric microbiome and H. pylori pathogenic status from gastric biopsies; 2) Determine the lower intestinal microbiome from stool samples of the endoscopy patients; 3) Analyze the association between H. pylori -altered gut microbiota and liver functions. Nine patients undergoing upper endoscopy examination in West Tallinn Central Hospital (Tallinn, Estonia) will be enrolled in the study. The proposal is designed as a pilot study and will be highly valuable cornerstone for further research involving bigger sample sizes.