Funded projects under the Grant Programme for SAS PhD students in 2020

The proposed project deals with the flexibility of working careers of employees at risk of automation, as the relevant literature assumes that their replacement by machines, ergo displacement can obstruct their movement on the labor market. Based on the theory of the transferability of the human capital and the presumed discrepancy between the skills acquired in education and the required skills in their profession, we want to verify the assumption that a significant part of employees in these professions have experience or qualification to perform another occupation, less endangered by automation

Hate speech is a complex phenomenon that is offensive or degrading, inciting violence against groups based on specific characteristics such as physical appearance, religion, national or ethnic origin, sexual orientation, gender identity or others. Hate speech has been growing in recent years, not only in face-to-face interactions, but also in online communication. Several factors contribute to this. On one hand, on the Internet and especially social networks in particular, people are more likely to behave aggressively because of the anonymity provided by these environments. On the other hand, people have an increased willingness to express their opinions online, thus contributing to the propagation of hate speech online. There are several definitions of hate speech on the Internet, coming from different sources. These are first of all directives coming from the European Union Commission, secondly definitions from minorities associations and non-governmental organizations, followed by scientific studies that provide an academic community's view, up to social networks conditions and terms (Facebook, YouTube and Twitter), because in these platforms hate speech occurs regularly. The aim of the project is to summarize and then analyse all individual existing definitions, while searching for their common and different features. For better understanding of the term, the project also looks into the related terms and their definitions, such as cyberbullying, extremism, hate crime. Given that there is still no agreement in the definition of the phenomenon of hate speech, our project aims to identify the indicators of hate speech, i.e. features that would more explicitly describe the phenomenon of hate speech. We are interested in the view of experts from the field as well as of ordinary people.

With growing immigration and increasing cultural diversity within countries, it is important to address issues of intergroup relations. It is necessary to understand the reasons for the occurrence of negative attitudes and reactions of young Slovaks to members from ethnic minorities. Focusing on mitigating feelings of threat is an effective tool in reducing negative intergroup attitudes. Our goal is to find out what effect the perceived threats from ethnic minorities have on the attitudes of young Slovaks towards these minorities. By examining different types of concerns and threats that young Slovaks feel and their impact on negative intergroup attitudes towards minorities, the work can serve as a resource for developing more effective methods of mitigating prejudice against these minorities so as to maximize the benefits of intergroup contact while minimizing intergroup threats.

The project aims to analyze the predictors of epistemically unfounded beliefs (next EUB). The study specifically focuses on the analysis of the relationships between pathological personality tendencies, existential issues, life satisfaction together with socio-demographic variables and EUB. Current EUBs include conspiracy and pseudo-scientific beliefs associated with the COVID-19 epidemic. This type of belief has a negative impact on attitudes related to healthy people (eg refusal to vaccinate) and is also a source of fear, which is misused by various extremist groups to provoke various maladaptive interpersonal interactions. These beliefs significantly reduce trust in authorities and institutions.

There seems to be a general agreement that oxidative stress is involved in many pathological conditions including Parkinson’s, Alzheimer’s, and other neurodegenerative diseases, and overall aging. Cerium oxide nanoparticles, also known as nanoceria (CeO2-NPs), have shown promise as catalytic antioxidants, based on their ability to switch between Ce3+ and Ce4+ valence states. The present proposal aims are to clarify the role of oxidative stress in age-related diseases characterized by presence of amyloid aggregates. We will use synthesized and natural compounds which are: i) associated with either, generation of oxidative stress or its elimination; and ii) capable to interfere with protein amyloid aggregation. We expect to better understand the mechanism of amyloidogenesis, link to oxidative stress and make progress in the finding a promising strategy for the modulation of amyloidogenic protein aggregation.

The structural behavior of magnetic fluids in magnetic fields is quite intuitive and scientifically well explored. In the field of fundamental research on magnetic fluids, there are well-known electric properties and phenomena, the understanding of which and subsequent practical applications in electrical engineering require deeper experimental study. Polarization, macroscopic structural changes of magnetic fluids in external electric fields and nanoscopic structure at magnetic fluid-solid interface belong to the currently discussed issues. Within the project, the progressive magnetic fluids based on insulating liquids will be investigated. The aim of the proposed project is the experimental investigation of bulk structural changes in magnetic fluids as well as the magnetic fluid-solid interfaces under the influence of various magnetic and electric fields. To attain the aim, neutron reflectometry and the small angle neutron and X-ray scattering will be employed as primary experimental methods.

Hybrid composites prepared by the sol-gel method have currently received attention due to their excellent combination of organic and inorganic parts in one material. The diversity of properties of such materials leads to a very broad range of their applications including water purification. The main aim of the project is the preparation of composite adsorbents based on silica and different types of polymers with carboxylic surface groups for the removal of inorganic (metal ions) and organic (basic dyes) pollutants from waters. Different variations of the sol-gel method will be applied and the synthesis conditions will be chosen to achieve better selectivity towards different metal ions and organic dyes. The advantage of the proposed method of synthesis is one-step, carrying out at room temperature, the use of environmentally friendly substances as solvents. The proposed approaches can be used to create adsorption composites with acid groups based on silica and polymers.

Recently, green technologies have attracted much attention due to environmental concerns. The project is focused on the verification of three strategies of silver selenide, Ag2Se mechanochemical synthesis, which is nanostructured semiconductor and perspective thermoelectric material. One-step direct synthesis from the precursors AgNO3 and SeO2 and two other two-steps synthetic pathways will be studied, whereby in the first step, Ag nanoparticles will be prepared by milling-induced reduction using a chemical or biological reducing agent. These hitherto unrealized processes represent a simple, low-cost, environmentally friendly, and solvent-free method with the potential for large-scale fabrication of Ag2Se. Innovative energy-saving technology is considered to be a promising way to relieve the impact on the environment. The project includes the monitoring of the kinetics of the proposed mechanochemical syntheses, an evaluation of the phase purity of the prepared products by X-ray powder diffractometry (XRPD), morphology characterization by scanning and transmission electron microscopy (SEM, TEM) and measurement of thermoelectric properties.

Objective of the project is development of Ohmic contacts for electronic devices based on gallium oxide (Ga2O3) ultra-wide band gap semiconductor. In comparison with other semiconducting materials, Ga2O3 provides possibility of preparing devices with high breakdown voltage (>10 kV) thanks to its large bandgap (4.6 – 5.3 eV depending on crystallographic phase). Our aim is to exploit high potential of α-Ga2O3, which originates from its higher bandgap compared to often studied monoclinic β-Ga2O3 and its crystallographic structure, allowing growth of heterostructures with other materials with corundum structure. These properties offer a great opportunity for processing of high-power electronic devices (diodes, high electron mobility transistors - HEMTs, etc.). In our project we propose systematic study and optimization of Ohmic contacts on α -Ga2O3 epitaxial layers grown by liquid-injection metal-organic chemical vapor deposition (LI-MOCVD) recently developed in our group. We will test various process conditions including conductive oxide deposition and ion-implantation. Gained knowledge will be used for further research and presented at scientific conference.

Recently, climate change has been one of the world's hottest topic. It can be seen also in Danube River Basin (to which a large part of the Slovakia belongs) and its manifestations are in the form of alternating dry periods and torrential rainfall. The mean air temperature rises, so there is more energy in the atmosphere to store moisture and it falls to the earth's surface in the form of intense storm showers. Heavy rainfall, which falls in a short time (several minutes), causes quickly drain of water from the surface, resulting in flash floods in smaller basins without streamflow gauges. Water streams after extreme rainfall reach culminations that have a low occurrence probability, and peak flow values help as important data in the regionalization of specific discharge with long repetition time.

The swarming behaviour of tree-dwelling bats is the set of specific behavioural displays in front of the roost, which are the most often propagated before the final entrance into the day roost during dawn. This behaviour has a signalling function during the roost switching (or selection of a new roost) as a consequence of changed conditions in former tree hollow and it also prevents this social group from disintegration. The aim of this project is to explore, if the level of glucocorticoids and testosterone, thus hormones which relate to induced stress or increased level of individual territoriality, correlate with the frequency of individual swarming behaviour in maternal groups of Daubenton’s bats.

The project will focus on the research of dragonflies and the evaluation of the current state and possible changes of wetland ecosystems in selected model sites within the territory of SW Slovakia. We will observe changes in the development of individual communities on the basis of the identified species spectrum of dragonflies, which are suitable bioindicators, as the occurrence of individual species of this series is linked to different successive stages and types of habitats. The sites will therefore represent different types of wetland ecosystems. The aim of the work will be the creation of a new methodology for assessing the population of dragonflies (Odonata) based on a combination of landscape ecological and zoological research. The importance of the project will be in obtaining new ways of evaluating this bioindicative species, both in terms of specifying the growing negative human impacts on the landscape and their effects on dragonfly populations and then proposing measures for appropriate management of these sites to minimize the factors that threaten dragonfly populations.

Antimony (Sb) is a metalloid gaining importance in recent years due to its toxicity. Both trivalent and pentavalent forms of Sb are taken up by plants even though they are non-essential. Trivalent form of Sb (SbIII) is more toxic compared to pentavalent form (SbV). Unlike other toxic metal(loid)s, uptake mechanisms of Sb are not well known. Yet Sb III is thought to enter the cell through aquaglyceroporins. Silicon (Si) is also a metalloid, proven beneficial to graminaceous plants such as sorghum by providing resistance to certain biotic and abiotic stresses. Impact of Si on uptake, translocation and accumulation of Sb is less investigated. Channel protein LSi1, belonging to NIP family is known to take part in Si uptake. Hence, this poses a question whether LSi1 can also assist in Sb uptake or not. Therefore, this study might help us to broaden our knowledge about Sb uptake in plants.

The photodynamic therapy (PDT) has a great potential as an alternative method of cancer treatment. PDT uses a photo-active drug (photosensitizer, PS), that has a high uptake by tumour cells and after illumination by the right wavelength and intensity it forces them to an apoptotic or necrotic pathway. The PDT may target directly the tumour cells, or the surrounding vessels that nourish the tumour. One of the perspective in vivo models for cancer research is the chorioallantoic membrane (CAM) of turkey embryo (Meleagris gallopavo). CAM has a rich vasculature that can sustain the growing tumours and, in contrast to the in vitro cultures, it offers an environment of a living organism, directly reacting to the therapy effects. The use of turkey CAM has several advantages against the use of more common chick CAM. Its longer development allows longer time period for experiments and longer cultivation of tumours. The larger size facilitates intravascular application of the therapeutic drugs. There is also evidence of higher survival rate of engrafted tumour cells and better metastases formation while using turkey CAM model. Our goal is to create a turkey CAM model with grown tumours of cervix adenocarcinoma using the HeLa cell line and apply the PDT with hypericin as the PS. We want to compare the effects of therapy after topical, or intravascular application of PS and evaluate the effect of PDT on surrounding healthy CAM tissue, including the changes in the vascular network.

Swainsonine (Fig. 1, 1) is an azabicyclic alkaloid, that atracts the attention of chemists mainly due to its biological activity. Swainsonine is one of the two known substances, that are potent inhibitors of Golgi α-mannosidase II (GM-II) which is involved in biosynthesis of N-glycans on the cell surface. According to current research, glycosylation is one of the key processes in metastasis, angiogenesis and other cancer conditions. Therefore, GM-II inhibitors became a suitable candidates for the development of anticancer drugs. Swainsonine, however, is not a suitable drug – besides the enzyme GM-II, it also inhibits lysosomal mannosidase which is responsible for the natural degradation of glycans in lysosomes. Thus, when developing anticancer drugs with the same target enzyme, it is desirable to look for swainsonine-like structures with the same potency, but with higher selectivity to GM-II. Based on PC modeling results, 5-benzylswaisonines (Fig. 1, 2a-e) could be suitable candidates.

The primary aim of this project is the design of a novel drug delivery system (DDS) to develop target drug delivery systems for transferring Tamoxifen drug (TAM) which is the most usage drug for breast cancer. For this propose, in the first step, the photo-responsive biocompatible polysaccharides based on the different ratios of the photo-responsive dye will be synthesized with a cheap and straightforward method. Smart photo-controllable release of the TAM due to higher complex constant of the Azobenzene dye (Azo) in side of Cucurbit[8]uril (CB8) cavity rather than the TAM:CB8 complex constant, and after photo-isomerization of Azo moieties (E to Z) with UV irradiation will be followed in the different pH. For this purpose, modification of polymer chain with the Azo moieties will generate the photo-responsible polymer which can widely use in different applications such as drug and enzyme delivery. The interesting structure of Azo groups can illuminate from trans to cis trough photo-isomerization under UV irradiation. Then, the complex of Tamoxifen:Cucurbit[8]uril (CB8:TAM) will be synthesized and characterized in aqueous solution. The mixture of the CB8:TAM with modified dextran will be represented a new interaction of Azo with CB as a second guest (Azo:CB8:TAM). The evaluation of cytotoxicity and biocompatibility for products will be followed in appropriated media. The overall objective of this project is to introduce the injectable breast drug delivery system that will be applied after the surgical removal of breast tumors suitable for controllable delivery of Tamoxifen in the long term. This approach is expected to decline the side effect of intravenous TAM trapping inside of cucurbit[8]uril. The optimum composition will be used for in vitro and in vivo for future research.

RNA-seq analysis of dbl2Δ transcriptome of Schizosaccharomyces pombe indicates that the deletion of dbl2 gene, that encodes a protein involved in DNA repair and homologous recombination, results in misregulation of more than 500 loci. Compared to the loci with no change in expression, the misregulated loci in dbl2Δ are statistically closer to the long terminal and long tandem repeats. Furthermore, the misregulated loci overlap with antisense transcripts, retrotransposons, meiotic genes and genes located in subtelomeric regions. A comparison of the expression profiles reveals that Dbl2 represses the same type of genes as the HIRA complex (histone chaperone complex) and Clr6 (histone deacetylase, H3-K9 specific). Interestingly, Dbl2 targets overlap with HIRA targets and simultaneous deletion of Dbl2 and HIRA (hip1, slm9), or Clr6 does not lead to a cumulative increase in expression, indicating that they function in the same pathway of gene expression. This project could elucidate the mechanism of the unexpected link between the homologous recombination pathway and HIRA histone chaperone.

The use of medicinal plants in the prevention and treatment of diseases has become part of veterinary medicine due to their promising therapeutic efficacy, minimal side effects, and the general effort to reduce the content of undesirable residues in foodstuffs of animal origin. In this context, the use of herbal nutraceuticals, which contain bioactive compounds (plant secondary metabolites), is offered as an alternative to chemotherapeutic and antibiotic treatment of diseases in ruminants. Herbal nutraceuticals are feeds that combine nutritional value with the beneficial effect of bioactive compounds on animal health. Sainfoin (Onobrychis viciifolia L.) is a medicinal plant with a high content of bioactive compounds (condensed tannins), which has a strong anthelmintic effect against gastrointestinal nematodes (GIN) represented by the parasite of small ruminants Haemonchus contortus. H. contortus causes a disease associated with significant losses in animal production parameters called haemonchosis. The aim of the presented project is to determine whether the administration of the sainfoin pellets affects the rumen fermentation, protozoan population, antioxidant activity, and hematological parameters of lambs with haemonchosis.

With the increased focus on alternative energy resources around the world, the nuclear energy industry is designing Molten Salt Reactor (MSR) as one of the candidates for the next-generation reactors, which meets the alternative energy needs. But, MSR with a eutectic mixture of LiF-NaF-KF as coolant medium is facing a hurdle with corrosion of construction materials in the melted salt environment. Many reasons have been proposed for the cause of the corrosion, but few of the core mechanisms like the stability of the fluoride layer formation and effect of impurities and activity of the salts still need to be fully understood. Our study suggests a three-phase experimentation process, to examine these phenomena in detail. The results of the experiments will identify and aide in corrosion prevention.

Neuropeptides are by far the largest and most diverse group of signalling molecules in multicellular organisms. Together with their specific receptors, they play an important role in neurotransmission, neuromodulation and are involved in the regulation of a diverse array of biological processes including reproduction, growth, circadian clock, ecdysis, feeding activity and metabolism. However, we have an insufficient information about their identity, function and expression level in pathogen-carrying vectors like the hard ticks Ixodidae. Based on our previous research, in situ hybridization and fluorescent immunohistochemistry disclosed cells producing short neuropeptide F (sNPF peptide) in the central nerve system and in peripheral tissues like gut. Homology-based search for sNPF receptors revealed two putative G protein-coupled receptors (sNPFR1 and sNPFR2) in the Ixodes ricinus genome. The aim of this project is measuring the sensitivity of sNPF peptide to both receptors and detection of sNPFR1 and sNPFR2 in central nerve system and peripheral tissues in I. ricinus.

Hypoxic stress in yeast is associated with fundamental changes in membrane sterol metabolism. In the present project, we will study the utilization of external sterols, especially mammalian cholesterol and plant sterols, as one of the adaptation mechanisms under hypoxic conditions. We will focus on the examination of the mechanisms by which yeast cells monitor the compatibility of the imported sterol with its membranes as a part of a concept called 'sterol quality control'. We will study the crucial components of the import, mainly plasma membrane sterol importers and sterol esterifying enzymes. In the view of the proposed concept, the physical and physiologically relevant properties of membranes in which native ergosterol has been replaced by sterols from the environment will be analyzed. The utilization of sterols from the host contributes to the resistance of pathogenic yeast to antifungals, hence the project has the potential to innovate existing or develop new antifungal drugs.

The potential use of mood stabilizers to recover mitochondrial function Barth syndrome (BTHS) is a serious genetic disease caused by a disorder in the biosynthesis of the special mitochondrial phospholipid cardiolipin. Cardiolipin deficiency leads to impairment of many mitochondrial functions, resulting in insufficient energy production in the form of ATP molecules. Impairment of mitochondrial metabolism is associated with several pathologies, including psychiatric illness. These are often treated with valproate (VPA). In our prior research, we have found a positive effect of VPA on impaired mitochondrial respiration and the activity of respiratory chain complexes in the yeast BTHS model. We subsequently extended the study to another model organism of BTHS, a TAZ-KO mutant created by the CRISPR / Cas9 system in the human haploid cancer line HAP1. Same as in yeast, we observed a positive effect of VPA on the activity of respiratory chain protein complexes in this model. However, the administration of VPA has a pleiotropic character. In the proposed project, we plan to verify the potential therapeutic effect of VPA on the harmonization of mitochondrial function in cells of the human BTHS model.

Comorbidity is defined as a coexistence of two or more diseases. Many patients with cancer are treated for other disease at the same time, for example cardiovascular diseases or type 2 diabetes. The treatment of these comorbidities may have an effect on the treatment of cancer. The effect of treatment of comorbidities on tumor cells has not been sufficiently investigated. Some drugs used for treatment of these comorbidities may contribute to a better prognosis of patients. Metformin, a drug used to treat type 2 diabetes, inhibits the growth and proliferation of tumor cells. Also some naturally occurring substances may have a positive effect in the treatment of cancer. Dipeptide carnosine is also connected with inhibition of tumor cells growth. Therefore, the aim of our work is to study the effect of metformin, carnosine and their combinations on the tumor microenvironment and carbonic anhydrase IX, a protein that contributes to the regulation of pH in the tumor microenvironment in 3D models of spheroids co-cultured with cells of the immune system. Combination therapy is currently one of the treatments of cancer because it can affect multiple signaling pathways or molecules simultaneously.

Traumatic brain injury (TBI) is caused by an external physical force and represents a major risk factor for development of neurodegenerative disease, such as chronic traumatic encephalopathy (CTE) later in life. Especially the harmful consequence of repetitive mild TBI (mTBI) has been described in the brains of contact sport players who suffered from depressive syndrome and developed CTE upon repeated concussive head impacts. Due to missing immediate visible symptoms and limited recent ability to identify mTBI, there is a need for a biofluid-based diagnostic test for TBI patients. MicroRNAs (miRNAs) are small, non-coding RNAs, which are present in all human biofluids and represent a valuable source of peripheral biomarkers. The main aim of this project is to identify a potential miRNA molecular markers for more precise diagnostics and follow up of symptoms after TBI and repetitive sub-concussive head impacts. Transcriptomic and bioinformatic analysis in a cohort of professional football players will lead to identification of signaling pathways reflecting the process of injury and brain recovery during the post-traumatic period when compared to the physiological conditions.

Despite outstanding advances in diagnosis and the treatment of the primary uveal melanoma (UM), outcomes for metastatic patients remain dismal. Nearly 50% of UM patients develop metastases via hematogenous dissemination, particularly to the liver and there remains no current standard assay for the detection of minimal residual disease. Exosomes are cell-derived vesicles and are abundant in biological fluids, containing RNA molecules that may serve as potential promising diagnostic biomarkers due to their cancer-specific expression profiles. We hypothesize that tumor-specific RNA fragments could be more densely concentrated in exosomes. The current study aims to assess exosomal RNA as a non-invasive biomarker in UM patients. For this reason, we determined to implement the optimal exosomal RNA extraction method from plasma to examine the expression of 5 top highly expressed genes in the UM tumors, that are not expressed in the peripheral blood of healthy donors. This can help us to identify new prognostic biomarkers, particularly important for patients who have not undergone enucleation.

Sexual reproduction depends on meiosis, a process that generates haploid gametes from a diploid precursor cell. Although it is well established that phosphorylation of proteins plays an important role in regulation of numerous cellular processes our understanding of dynamics of meiotic phosphoproteome is still limited. The fission yeast S. pombe is a useful model organism for studying meiosis. Despite temperature sensitive pat1-114 allele was crucial for deciphering the basic principles of meiotic cell division in S. pombe, it was the conditional ATP analog-sensitive pat1-as2 allele which led to a highly synchronous meiosis with suppressed mono-orientation defects of sister kinetochores. Unfavourably, the pat1-as2 mutant, due to the method used for its creation, contains leftover carrier DNA sequences in its genome. It is generally accepted that incorporated redundant sequences might interfere with expression of genes of interest along with genes occurring in its proximity. My goal will be to create genetically clean pat1-as-crispr mutants utilizing the genome editing tool CRISPR/Cas9 (SpEDIT). Created pat1-as-crispr mutants will be further characterized and their meiotic features will be compared to known pat1-114 and pat1-as2 mutants. Finally, even it is behind the scope of the proposed project, the newly created pat1-as-crispr mutants will be incorporated into our ongoing project that follows the dynamic changes in phosphorylation of proteins during various stages of meiosis. Unarguably, mapping the dynamics of protein phosphorylation during particular stages of meiosis might identify important regulatory mechanisms of meiosis-specific processes.

The hippocampus is an important structure of the limbic system, involved in the modulation of emotions, memory and learning. It is also crucial brain structure undergoing neuroplasticity processes including neurogenesis until adult age. Hippocampal neurogenesis is under control of numerous extrinsic and intrinsic factors supporting the growth, survival and differentiation of neuronal cells. One of the crucial molecules involved in the regulation of neurogenesis is oxytocin (OXT). Another molecule implicated in modulation of hippocampal neurogenesis is the brain-derived neurotrophic factor (BDNF). Impaired production of BDNF and OXT can result in a disruption of neurogenesis and lead to various neurodevelopmental disorders. Therefore is important to investigate the role oxytocin in BDNF signaling pathways. The aim of the present study is to determine the effect of oxytocin administration in early development on BDNF levels and its precursors in the hippocampus. Moreover, several parameters of the BDNF signaling pathways will be evaluated in response to oxytocin treatment as well. The proposed project will contribute to the understanding of the role of oxytocin in the regulation of neurogenesis in early development.

Peripheral nerve injury is a serious clinical problem that, without medical treatment, leads to loss of motor and sensitive functions in the innervated area. Despite the fact that peripheral nerve axons regenerate spontaneously, satisfactory results are achieved after standard treatment in only about 50% of cases. In our experiments, we use a model of ventral tail nerve injury in the rat, and we test innovative methods of reconstruction of the damaged nerve. We want to objectively evaluate the success of regeneration (number of regenerating axons) in the distal nerve stump by retrograde labeling of their motoneurons. The aim of the present project is to apply a retrograde fluorescent marker (Fluorogold) locally to the peripheral nerve, and to introduce a new method of imaging and quantification of the labeled motoneurons in the spinal cord using the tissue clearing method. Using this imaging method, we will evaluate the numbers of marked neurons in 3 groups of animals: 1, control 2, axonotmesis (degeneration of axons while maintaining optimal conditions for their regeneration) 3, nerve transection and reconstruction by tubulation (synthetic conduit fixed with tissue adhesives). The results of the experiments will be a detailed description of the topography and segmental distribution of motoneurons innervating the rat ventral tail nerve, including their quantification. For two different types of peripheral nerve injuries, we will document the numbers of neurons capable of regenerating their axons. These data will be used as reference data in further experiments focused on the ability of axons to regenerate through different types of synthetic conduits.

Acidosis and hypoxia are common features of the tumor microenvironment and contribute to cancer aggressiveness, progression, and resistance to therapy. While the negative effects of a low extracellular pH in the tumor milieu are well established, the underlying mechanisms are largely still unknown. One of the most strict hypoxia-regulated tumor-associated genes, carbonic anhydrase IX (CA IX), is a transmembrane metalloenzyme involved in tumor pH regulation, cell-adhesion, spreading and migration. By studying long-term acid-adapted cancer cell lines BxPC3 and HT1080 cultivated in 2D and 3D cultures, this projects aims to shed more light on the mechanisms upon which acidosis acts on. While mainly focusing on CA IX expression in relation to the extracellularly acidic niche, we would like to establish a solid base for the potential use of anti-CA IX antibodies in combination therapy.

Global ageing of human population inevitably leads to an increased number of patients diagnosed with neurodegeneration. Alzheimer´s disease (AD), characterized by progressive decline of memory and cognition, represents the most prevalent type of neurodegenerative disorder. The pathological changes in the brain appear decades before manifestation of clinical symptoms. The recent gaps in diagnostics of AD directs the research to the identification of novel biomarkers that are needed for early and specific diagnostics of AD patients. The data from several studies indicate a strong potential of non-coding RNAs (microRNAs and long non-coding RNAs - lncRNAs) as promising biomarkers. The main goal of this study is to identify differentially expressed miRNAs and lncRNAs in plasma of AD patients that would represent a panel of potential circulating biomarkers for AD. Furthermore, employing a state of the art bioinformatic workflow we plan to characterize signalling pathways including novel molecular interactions linked to the Alzheimer's disease pathogenesis. This approach could discover new original data for the understanding of neuropathogenesis and biomarkers for AD.