Projects

Design and testing of antihypertriglyceridemic peptides in human plasma

The project is focused on the development of a new energy and source efficient transformation, which can be potentially integrated into an industrial process. Synthetic electrochemistry attracts more and more attention as an alternative to classical thermochemical reactions that require toxic and expensive transition-metal-catalysts or stoichiometric amounts of harmful and wasteful oxidants. In electrochemical reactions, electrons are used as “traceless and green reagents” to generate highly reactive radical particles under the mild reaction condition providing access to the previously unapproachable reaction pathways. Moreover, the potential to harvest sustainable solar or wind energy makes electrochemistry even more attractive. In the framework of this project, we have successfully demonstrated a novel electrochemical approach for the synthesis of aryl oxygen compounds that does not require the use of oxidants nor metal catalysts. These type of compounds are widely used precursors for synthesis of valuable polymers, complex bioactive molecules and are common structural motifs in many natural products. In our research we have used an inexpensive self-manufactured setup to perform electrochemical transformation in continuous-flow, which allowed us to develop a reliable and scalable process that makes it particularly interesting for the chemical industry.

The most significant results of this project include developing a user-friendly tool for microbiology studies. This tool was used to figure out how growth of individual bacteria cells varies during exposure to different metals. This vital knowledge will contribute to ongoing experiments about the possibility of metals affecting individual bacteria cells’ ability to grow in the presence of antibiotics, and to overall research in antibacterial substances and antibiotic resistance. The newly developed tool has also opened the door for future experiments and new collaboration projects both regionally and internationally. Researchers and students alike, no matter their educational or financial background, will be able to apply the tool for their own research topic. Through this project the PI has obtained valuable insight into leadership, experimental procedures, networking, and writing which has contributed to development into an independent researcher.

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.

R&D work is preliminary study for industrial measurement techniques

ECAC unites the competence and analytical capabilities of three prominent organizations in Estonia: University of Tartu, Tallinn University of Technology and the Estonian Environmental Research Centre and offers access to analytical instruments as well as services and collaboration both to academia and industry.This network enables the use of analytical apparatus in an optimal way and avoids duplication. The main objectives of ECAC are: (1) to create a “cross-user network” between research institutions. This allows the users easily to carry out complex projects, which require advanced apparatus. In addition, it avoids the duplication of the equipment (Objectives 1, 2.1, 2.3, 2.4). (2) to be an innovation and technology development support unit for R&D projects and industrial innovation (incl. to achieve the goals of a smart specialisation) (Objective 1) (3) to be the center of analytical chemistry education and knowledge transfer (Objective 3); (4) to be the support structure in analytical chemistry for Estonia's participation in various EU cooperation networks such as ESA, Eurachem, Euramet / EMPIR (Objectives 2.2, 3).

There is a high risk that the coronavirus (SARS-CoV-2 variants) continues to spread in its specific forms, including through direct contact with surfaces, and this will require effective materials and sterilization methods. Ethanol-based products have advantage in the direct contact, but we have developed surfactants with different and wider uses for disinfection. The new disinfectants contain biodegradable ingredients that remain on the surface much longer to inactivate bacteria, viruses, fungi and material viruses, incl. coronavirus. The range of new products includes: (1) POM / PLA composites made by the melt extrusion process and well suited as a coating material for the hospital environment; (2) nanoemulsions of essential oils that characterized by controlled loading; (3) treated highly hydrophobic surfaces, (4) lignin-based materials (as gels and films), which also have antiviral and antibacterial properties. They are classes of products worth developing and that our Estonian entrepreneurs could use.

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.

Regulation of Lipoprotein Lipase Activity in Human Plasma

In the case of impaired cerebrospinal fluid absorption, or hydrocephalus, the pressure in the cerebral cortex increases, which also narrows the blood vessels that supply the brain, and thus the dynamics of blood flow pulsations in these blood vessels change. The dynamics of blood pulsations change in a similar way in the case of narrowing of the blood vessels, which is caused, for example, by calcification of the arteries of the leg. Both situations would require a simple, repeatable, and inexpensive diagnostic method for early detection and monitoring of changes. Therefore, the aim of the postdoctoral project and a study carried out at the City University of London was to investigate the effect of constriction on the pulsating optical signal recorded from an artery and to develop an optical method to detect the constriction. An arterial system was developed consisting of a pump and tubing that created different levels of fluid flow obstruction. Suitable optical sensors were built to record the optical signal from the tubes and later from the arteries. In the built arterial system, an optical signal related to the change in blood volume and flow was recorded before and after the induced constriction in the tube. Characteristic changes were detected in the signals, which are directly related to narrowing of the arteries mimicking tubes. As follows, the study was carried out in a small group of subjects, in which the constriction in the arm arteries was artificially induced at different levels. The changes detected from the optical pulsating signal recorded from the artery of the arm were consistent with the changes in the optical signal found in the constructed model. These results provide some confidence that this method and optical technology can be used to detect narrowing of the arteries. However, further studies are needed, for example in patients with calcified leg arteries, and thus to monitor and, if necessary, to improve this methodology.

A prototype allowing a rapid diagnostic possibility of COVID-19 has been developed. The principle of operation of the prototype differs drastically from widespread lateral flow COVID-19 express diagnostics tests currently available on the market. Namely, the prototype is a combination of sensor chip modified with the synthetic receptor and a portable potentiostat. The synthetic receptors were prepared by molecularly imprinting technology and targeted against nucleocapsid (N) and spike (S) SARS-CoV-2 viral proteins. It was shown that the prototype was capable of detecting the target proteins from patients’ nasopharyngeal samples in 15 min through measurement of the redox reaction intensity at the chip after its incubation in the mentioned sample. The prototype has the following advantages over lateral flow tests: (i) employment of the synthetic receptors as sensitive elements instead of their biological counterparts provides a more cost effective and stable diagnostics tool in whole; (ii) about hundredfold lower LOD allows diagnosis of COVID-19 at earlier stage; (iii) measurement of concentration of the proteins allows estimate viral load. Therefore, the prototype has the outstanding innovative potential for its further development to offer a reliable COVID-19 express diagnostic tool. Such a tool can be employed in clinical institutions for example in primary care physician practices, emergency medicine etc. The tool could be also developed for point-of-care and personal use at home as well in order to reduce load on healthcare systems and prevent additional risks for passing on the infection to other people. It should be noted that in this project we managed, for the first time to the best of our knowledge, to apply the molecular imprinting technology for detection of SARS-CoV-2 viral proteins. The results were published as a scientific paper in the top interdisciplinary journal devoted to biosensors, which has already received multiple citations.

The aim of the current project was to develop, test, troubleshoot, and validate the portable drug analyzer (previously called AiD) Drug Hunter (www.drughunter.eu) suitable for roadside drug testing in oral fluid by non-chemists operators such as police officers. Drug Hunter combines two powerful techniques in one box: capillary electrophoresis (CE) and deep UV fluorescence detection. Drug Hunter Analyzer solves multiple technological gaps of immunoassay tests (high error rates, control strip failure, only qualitative results, detection of illegal drug classes), providing immediate quantitative results for each drug even in multidrug abuse cases. The main project outcome was the thorough troubleshooting, testing, validation, and functionalities improvements of the Drug Hunter analyzer for the real operation conditions in cooperation with Estonian police. The main achievement was the development of a new oral fluid collection and treatment procedure that helped to resolve the issue, i.e. the lack of oral fluid due to the dry mouth effect. Another achievement is dedicated to the increased sensitivity of amphetamines and the overall analysis speed-up. The cut-off limits of Drug Hunter met the DRUID recommended cut-off limits. Based on the results of the validation, the methodology complies with the requirements of the European Medicine Agency (EMA) for bioanalytical method validation. Drug Hunter is a pre-commercial scale detection apparatus for illegal drugs to a quality level and simple enough to be used in the field handled by various professionals (police, custom workers, prison guards, and various transport situations). Drug Analyzer analyzer is protected by patent.

The aim of project is the determination of physico-chemical, antibacterial, bioactive and antioxidative properties of Estonian honeys as well as their effect on human heath.

The project aimed to launch and pilot work-based learning in the Business Information Technology (IABM) curriculum. Over two years, at least 11 Masters of IABM had to be awarded a diploma who performed 50% of their studies in the workplace by acquiring the competencies and learning outcomes of the IABM curriculum. The project resulted in changes to the IABM curriculum: four work-based project subjects were added. These four project subjects, together with the project management subject and master thesis, enable IABM students to acquire 50% of the curriculum on a job-based basis.