Our successes in the National Science Center competitions OPUS 25 and PRELUDIUM! | Faculty of Chemistry at the Gdańsk University of Technology

As many as three projects will be implemented at our Faculty thanks to funding under the OPUS 25 competition. These are: “Compounds modulating the functions of telomeric proteins TRF1 and TRF2”, project leader: prof. Maciej Bagiński, co-financing amount PLN 2,813,440.00; “New monovalent and multivalent recombinant proteins of Borrelia burgdorferi sensu lato as potential antigens for detecting specific antibodies in the sera of patients with Lyme disease”, project leader: Lucyna Holec-Gąsior, PhD, DSc, Eng., university professor, co-financing amount: PLN 1,507,920.00 and “Study of the coordinated regulation of the amount of lipopolysaccharides (LPS) and phospholipids by the essential LPS assembly proteins LapB/LapC and by the participation of a new thioesterase”, project leader: prof. Satish Raina, PhD, co-financing amount: PLN 1,812,920.00.

In turn, the project “Oxidative stress signature in coronary heart disease”, implemented thanks to OPUS 25 financing under the supervision of prof. Miłosz Jaguszewski from the Medical University of Gdańsk, will be implemented in partnership with Anna Stanisławska-Sachadyn, PhD, DSc, Eng., university professor, co-financing amount: PLN 2,186,884.00.

The PRELUDIUM program will finance three projects implemented at our Faculty:

• Project “Development of bifunctional layers with osteoinductive and anti-oncogenic properties on metallic implants dedicated to bone reconstruction after cancer resection obtained as a result of two-stage micro-arc oxidation with ultrasound”, project leader: Balbina Makurat-Kasprolewicz, MSc, Eng., project supervisor: Mohammad Reza Saeb, PhD, Eng. Co-financing amount: PLN 209,880.00 (PRELUDIUM program)
• Project “Machine learning in the meta-learning version as a tool to guide the experimental improvement of the sorption properties of ionic liquids”, project leader: Karol Baran, MSc, Eng., project supervisor: Adam Mirosław Kloskowski, PhD, DSc, Eng. Co-financing amount: PLN 195,505.00 (PRELUDIUM program).
• Project “Assessment of the potential toxicological risk associated with the consumption of nucleic acids oxidized during thermal processing of meat products”, project leader: Anna Kościelak, MSc, Eng., project supervisor: prof. Agnieszka Bartoszek-Pączkowska, PhD, DSc, Eng. Co-financing amount: PLN 139,934.00 (PRELUDIUM program).

All these projects aim to solve problems that are important for the development of science:

“Compounds modulating the functions of telomeric proteins TRF1 and TRF2”

Compounds that modulate the functions of telomeric proteins TRF1 and TRF2 Telomere proteins called shelterins are an important structural and functional element that protects the ends of chromosomes of eukaryotic cells, including human cells. The proper functioning of these proteins ensures proper cell division and protects the ends of telomeric DNA against damage. For several years, it has been postulated that TRF1 and TRF2 proteins may constitute a new molecular target in anticancer chemotherapy. The project is a continuation of an earlier project in which we managed to find leading compounds that block the interaction of TRF1 and TRF2 proteins with the TIN2 protein. These are two low molecular weight compounds. In the current project, the goal is to expand these studies by searching for derivatives of these compounds that demonstrate even better chemotherapeutic parameters. The project would include in silico design of new derivatives based on already known lead molecules. Then, these compounds would be synthesized and their properties would be determined in vitro (including blocking the TRF1/2-TIN2 interaction) and in vivo (biological effects in cell cultures).

“New monovalent and multivalent recombinant proteins of Borrelia burgdorferi sensu lato as potential antigens for the detection of specific antibodies in the sera of patients with Lyme disease”

The diagnosis of Lyme borreliosis, an infection caused by spirochetes from the Borrelia burgdorferi sensu lato (sl) species complex, is based mainly on clinical symptoms supported by serological tests and is often misdiagnosed in endemic areas. In Central and Eastern Europe, Lyme disease is most often caused by B. burgdorferi sensu stricto (ss), B. garinii, B. afzelii, although other European species such as B. valaisiana, B. lusitaniae, B. bisettii and B. spielmanii have also been isolated from body fluids and tissues of patients with symptoms of Lyme disease. The complexity of the antigenic composition of Borrelia genospecies and the differential expression of genes encoding individual antigenic proteins in the host and vector (i.e. temporal and spatial antigenic variability) constitute extremely important challenges for the correct serodiagnosis of Lyme disease. Despite many efforts, correct diagnosis of this disease still encounters many difficulties. For this reason, it is extremely important to conduct basic research aimed at selecting, obtaining and testing the antigenic properties of new recombinant proteins with potential diagnostic utility. For this reason, the aim of this research project is to obtain new, original monovalent and multivalent recombinant B. burgdorferi sl proteins in a prokaryotic expression system and then determine their antigenic properties.

“Study of the coordinated regulation of the amount of lipopolysaccharides (LPS) and phospholipids by the essential LPS assembly proteins LapB/LapC and by the participation of a new thioesterase”

The most defining and distinguishing feature of Gram-negative bacteria such as Escherichia coli is the presence of an asymmetric outer membrane (OM), which is essential for their viability. This asymmetry results from the presence of lipopolysaccharide (LPS) in the outer layer of the OM and phospholipids in the inner part. LPS is one of the most important virulence factors of pathogenic bacteria and is the cause of bacterial sepsis. LPS covers nearly 70% of the cell surface, and its synthesis and translocation to the OM requires over 50 genes, of which approximately 30 are essential for life, constituting 10% of all genes essential for life in E. coli. Because many of them are key and unique to bacteria, they are attractive targets for discovering new antibiotics and vaccines. For sustainable growth in bacteria, there must be a strict balance between phospholipids and LPS, which share a common metabolic precursor. Any disturbance in the LPS to phospholipid ratio causes the death of the bacteria. This balance is achieved by regulating the amount of the LpxC protein, which catalyzes the first irreversible step of LPS biosynthesis, and by the FabZ enzyme, which initiates the synthesis of phospholipids. LpxC is an unstable protein whose stability is controlled by many factors. Over the past few years, the team has shown that the FtsH and LapB proteins mediate the proteolysis of LpxC, and the newly discovered essential protein LapC inhibits LapB activity and prevents unwanted removal of LpxC. Since it is not known how the activity of LapB and LapC is regulated in response to the demand for LPS, and which amino acids in LapB and LapC mediate the interaction with LPS, these aspects are the subject of research in this project.

“Oxidative stress signature in coronary artery disease”

Cardiovascular disease (CVD) is a multifactorial disorder and, according to the World Health Organization (WHO), it is still the largest cause of death in the world. In the light of the latest research, it seems that oxidative stress may play a key role in the development and progression of atherosclerosis. Direct measurement of free radicals in the body is difficult because their half-life is very short and therefore they do not accumulate in sufficient amounts to be detected. However, there are some indirect ways of measuring oxidative stress in the blood that can be used. A population of individuals who underwent low-dose computed tomography (LDCT) screening for lung cancer in 2016-2017 was selected for the current project. The study included people who had not been diagnosed with cancer, but were diagnosed with coronary atherosclerosis defined as the coronary artery calcium score (CAC score) - as an additional parameter. People with healthy coronary arteries were selected as a control group for comparison. It is planned to carry out a wide-scale molecular analysis related to oxidative stress in this group of people: analysis of the extended lipid profile, biochemical parameters, determination of non-targeted metabolomics, microRNA levels and genetic polymorphisms (SNVs).

We congratulate all the winners on their success and wish them satisfaction with their research!