SCIENTIFIC RESEARCH

The research under the NAWA project will concern a wide area of veterinary medicine - both reproduc-tive biology, research on biosecurity in the context of drug residues, safety of food of animal origin (drug resistance of bacteria, especially staphylococci), oxidative stress in metabolic and cardiological diseases and veterinary oncology.

1. Research on assisted reproductive techniques in animals

The aim of the task is to conduct international research in the field of reproduction, in particular the application of reproductive biotechnologies in animals. UPWr and Partners (ENVA, UGent, UniMi and Vetmeduni) have many years of experience and an established position in this field. The research will focus on three areas.

The first area is translational research with the use of biomedical animal models to analyze the impact of civilization factors on the reproductive potential. In this regard, in vitro simulations of the impact of thermal stress and endocrine disruptors on isolated gametes and embryos will be carried out.

The second area is the protection of biodiversity through the use of assisted reproductive techniques in safeguard programs for the populations of endangered animal species. The work will be carried out on gametes and embryos of domestic cats and dogs, as model animals for wild felids and canines, and on reproductive cells from wild animals threatened with extinction. The research will be used to build a network of European centers involved in the creation of a gene bank for these species and to create a European platform for increasing competences, exchange of biological material, information flow and mobility.

The third area is the field of veterinary reproduction, where the animal is treated as a target. In this area, the research will concern joint experiments on the issues of embryo transfer and assisted reproductive techniques in horses and production and companion animals, male and female infertility, and modification of gamete properties in order to improve the results of their conservation and artificial insemination.

2. Study of the population kinetics of drugs in laying poultry using nonlinear mixed effects modeling

Research in the field of biosecurity will focus on nonlinear mixed effects modelling (NLME) as an advanced tool in predicting the risk of drug residues in animal products (consumer safety). The cooperation will include studies on the pharmacokinetics of selected veterinary drugs in laying hens and their transfer to eggs. Due to the recently publicized cases of illegal use of antiparasitic drugs in laying hens and their residues in table eggs, it is planned to focus on representatives of this pharmacological group. Through the use of advanced population modelling, factors of variation (physiological, behavioral, etc.) that influence the risk of drug residues in animal products will be identified. Experimental studies and chromatographic analyzes will be carried out in Wrocław, and the delegated PhD students will go with the raw data to ISU to learn NLME under the supervision of outstanding specialists by developing specific models explaining the pharmacokinetics of drugs.

3. Research on oxidative stress in heart diseases

Research in the field of biomedicine will focus on the use of an animal model (dog, rat) in the study of oxidative stress in cardiological and metabolic diseases. Translational research is currently a dynamically developing field, and cardiology, neurology, oncology, autoimmune diseases and regenerative medicine are priority areas from the point of view of human medicine. Detailed knowledge of pathophysiological mechanisms, reactions to new substances or biomaterials is necessary to implement new therapies in civilization diseases.

Currently, oxidative stress is considered an important component of the pathophysiology of heart disease in both animals and humans. In addition to assessing oxidative stress in heart disease, substances that could be used to reduce oxidative stress are also being sought. Such studies are usually carried out in animal models, where the most common model organisms for humans are the rat, dog and pig.

As part of the planned research in Poland, the parameters of oxidative stress in dogs with heart failure and in rats with metabolic syndrome will be determined. In rats with metabolic syndrome, polyphenols obtained in an innovative way from pomegranate skins will be administered as substances reducing oxidative stress. The team of UPWr scientists has the knowledge and experience to conduct research in this field effectively, therefore the experimental part will be conducted in Poland, and advanced population modeling will be carried out at the Partner (ISU).

The use of advanced population modeling is of fundamental importance in the development of translational medicine research, as it allows to maximize the obtained results while minimizing the number of animals in the study group, which is in line with the 3R principle (replacement, reduction, refinment). In addition, the use of NLME modeling will allow for a better understanding of the sources of variability in response to the administration of the research factor depending on the coexisting pathological processes.

4. Studies on the structure of the population of pathogenic Staphylococcus species

Safety of food of animal origin is a key element of the One Health concept. Research in the field of biosecurity will be conducted in cooperation with The Milner Center for Evolution, University of Bath. The aim of the task is to analyze the population structure and the mechanisms of acquiring virulence traits by pathogenic species of bacteria of the genus Staphylococcus.

In our research, we plan to determine the genomic sequence of about 40 Staphylococcus isolates from farm animals and analyze the similarity of these sequences with the genomic sequences of about 1,600 Staphylococcus spp. Isolates, stored in the Milner Center for Evolution databases. The comparison will be made using the whole genome MLST. We assume that the results of these studies will allow to understand the molecular mechanisms of the evolution of genomic islands containing genes of staphylococcal enterotoxins present in the genomes of bacteria of the genus Staphylococcus.

5. Research and development works on the biology of canine tumors

The joint research project of UPWr and UniPd will focus on research into deepening the knowledge of the biology of canine tumors, especially in the context of DNA repair disorders, which on the one hand are considered to be the cause of cancer, but also a potential therapeutic target.

The use of modern molecular biology techniques, consisting in the analysis of the entire genome, transcriptome and methylome in neoplastic cells of the dog, will be of greatest importance here. Such a scientific approach will allow the identification of disorders in the cancer cell, which in turn will allow for the development of a modern, personalized therapy for a given patient.

Characterization of the molecular basis of genetic instability in selected types of cancer in dogs and their susceptibility to the use of PARP inhibitors (PARPi) will be the basis for the development of new therapeutic protocols using PARP inhibitors alone and / or in combination with known genotoxic drugs (e.g. platinum derivatives, antimetabolites, hypomethylating agents). A complete characterization of changes occurring at the level of gene expression and proteins associated with DNA damage / repair, as well as their role in other signaling pathways, will be a starting point for identifying potential biomarkers of DNA damage sensitivity, but will also be key in predicting patient response to newly developed schemas therapeutic with PARP inhibitors. The planned study will also be of great practical importance, as the tests will be performed on cancer cells obtained from sick dogs.

Research is also important in terms of biomedicine - dogs show tumors that are also found in humans, which makes the dog an excellent model for research. Therefore, multidisciplinary comparative oncology projects are now of fundamental importance. The research on the mechanisms of DNA damage and repair in canine cells using modern techniques developed by Professor Dacasto's team will be the first project of this type in veterinary oncology.