Mitochondria, which act as small 'powerplants', are essential for almost every human cell to function properly. The dysregulation of these organelles is associated with numerous diseases, including cancer, neurodegeneration and aberrant inflammatory response. In order to function properly, mitochondria import some proteins that are made elsewhere in the cell. One such protein is polynucleotide phosphorylase (PNPase), an RNA-degrading enzyme found in many organisms. Mutants of hPNPase are found in humans with various disorders, mainly neurological, highlighting the importance of this protein in regulation of mitochondrial metabolism. Some hPNPase is also located in the mitochondrial matrix, where it interacts with another protein, Suv3 helicase, to destroy superfluous RNA. However, most of the human PNPase is located in the mitochondrial intermembrane space (IMS), the area between the two membranes surrounding the mitochondrial matrix, where its role is puzzling. dr Katarzyna Bandyra, fot. Michał Łepecki

I have been familiar with PNPase for a long time, as I have studied the functions of this enzyme in bacteria. It is well known that bacterial PNPase participates in the degradation and processing of RNA. I have discovered that it can also form a complex with another protein and RNA, so that its function turns 180 degrees and, instead of degrading RNA, it begins to protect it. In this way, one enzyme, whose primary function is to destroy RNA, under certain conditions also acts as an RNA chaperone. Both human and bacterial PNPase are very similar in sequence and structure, so it is possible that they have similar functions as well.

My research focuses on understanding the function of human PNPase in the mitochondrial intermembrane space. My hypothesis is that the human PNPase, similarly to the bacterial enzyme, could protect RNA, and this could be its role in IMS. Switching of hPNPase activity could occur in the presence of a special type of RNA that hPNPase could not destroy, or another protein, as in the case of bacterial PNPase. On the other hand, in the mitochondrial matrix hPNPase together with the Suv3 protein would degrade RNA. This way, by physical separation of the pool of hPNPase into two different compartments, both its activities could be supporting optimal performance of the mitochondria.

dr Katarzyna Bandyra, fot. Michał Łepecki In order to test whether human PNPase can have two different functions in mitochondria, I am carrying out experiments using biochemistry, biophysics and molecular and structural biology techniques. Their aim is to determine whether, in addition to RNA degradation, hPNPase functions as an RNA-dependent regulatory protein that protects RNA, e.g. during transport into or out of mitochondria. In addition to studies of hPNPase itself, I am developing a method to obtain information about other proteins and RNA molecules interacting with hPNPase directly in human cells. To this end, I am isolating mitochondria and separating them into fractions that correspond to IMS or matrix, and then performing pull-down experiments to compare protein and RNA partners of hPNPase at different locations. Moreover, I will investigate complexes of hPNPase with the identified proteins and RNAs in vitro, and for the most stable ones I will determine the precise three-dimensional structure using cryo-electron microscopy. These studies will help to understand the role of human PNPase in the mitochondrial intermembrane space and are a prelude to a long-term research plan that may contribute to the development of gene therapies for mitochondrial diseases.

This interdisciplinary research project, which combined culture studies, anthropology, gender studies and sociology, analysed how the Kurds, a nation without state structures and state institutions, have operated outside such structures, independently building social and cultural institutions of their own in their respective countries of citizenship. Over the last five years, the Kurdistan region, located in the heart of the Middle East and divided between four nation states (Iran, Iraq, Syria and Turkey), has experienced a series of profound transformations. Some brought hope and inspiration to the Kurds, while others meant that their rights were violated. Even though they often led to the relocation of entire communities and the destruction of many institutions, many new activists and organisations emerged both in the Kurdish homeland and across the diaspora.

The team during a seminar at the Fafo Institute in Oslo in 2022. Both internationally and locally, the Kurds are better known for their guerrilla struggle and violent confrontations than peaceful activism. The focus on violence, both in academia and in the media, has led to the relative invisibility of Kurdish social and cultural activism, even though such activism has profoundly transformed the Kurdish community from within. Despite the constraints put in place by state oppression, local cultural centres and women’s organisations, as well as individual actors, such as artists, writers and intellectuals, have all contributed to shaping new narratives and moral imaginations. Since the voice and the activism of women have been generally given short shrift, the goal of ALCITfem is to focus, precisely, on the role of women, as well as the moral ideas and narratives surrounding the social position of men and women. Our project relies on the concept of alternative citizenship to highlight that the Kurds have developed multiple alternative strategies of action (both political and non-political) that remain outside the sphere of state institutions and their structures.

Within the framework of ALCITfem, team members, who spoke the necessary local languages, conducted research in the main centres of Kurdish activism both in Kurdistan and in the diaspora. Alternative citizenship was looked at through the prism of two mutually dependent spaces: activism initiated by women and its moral and cultural foundations. These research problems were investigated within the following four subject areas: 1) the representation of women in Kurdish culture and its role in shaping civic attitudes; 2) the covert activism of Kurdish women; 3) the shaping of gender roles in Kurdish families; and 4) eco-feminism. In this way, the project combined an interest in visible and hidden practices with an attention to the way in which activism was embedded in moral and cultural traditions. Alongside publishing our research results, we also organised several photo exhibitions in cooperation with the Museum of Asia and the Pacific in Warsaw and the Manggha Museum of Japanese Art and Technology in Kraków.

In terms of theory and methodology, the ALCITfem project, Activism And Its Moral and Cultural Foundation: Alternative Citizenship and Women’s Roles in Kurdistan and the Diaspora, combined the fields of social studies and the humanities through the cooperation of the following departments: the Section of Kurdish Studies at the Institute of Oriental Studies (Faculty of Philology) of the Jagiellonian University (PSK IO UJ, Kraków); the Centre for Gender Research (STK, Senter for Tverrfaglig Kjonnsforskning) at the University of Oslo (UiO); the Center for the Advanced Study of Population and Religion (CASPAR) at the Krakow University of Economics (UEK); the Fafo, Institute of Labor and Social Research in Oslo; and the Asia and Pacific Museum in Warsaw.

The main objective of the project is to identify, describe and analyse unequivocal evidence, hitherto unavailable in Europe, for extreme glacial events and, specifically, for sudden discharges of large quantities of meltwaters and surges in the periphery of the ice sheet during the last glaciation period. Our research thus far has allowed us to identify the landforms that suggest such extreme glacial events indeed took place and the processes involved in their evolution, which were previously unknown for the north-eastern Poland or in even southern periphery of the last Scandinavian ice sheet.

Field studies at the research station in Biała Woda, north of Suwałki (standing from the left: W. Wysota, A. Krawiec, P. Weckwerth (PI in an NCN grant), M. Chabowski, D. Kumar, E. Kalińska). Photo by Andrzej Romański In our project, we reconstructed the processes that shaped such landforms and led to the deposition of sediments under the ice sheet and within the ice stream in the vicinity of the town of Rajgród. It was the first time that ribbed moraine landforms were identified in north-eastern Poland, represented by groups of parallel ridges orientated transverse to the ice flow, which were formed sub-glacially (under the ice sheet) as a result of the quick advance of the glacier, whose pressure deformed the bedrock. On the other hand, by identifying the morphology, geological structure and origins of landforms created by catastrophic glacial floods near Suwałki (north-eastern Poland), we were able to understand the processes by which such floods transported and deposited various sediments, their energy and flow regimes, as well as their flow parameters (depth, speed, hydraulic gradient, etc.).

Dr hab. Piotr Weckwerth, photo by Michał Łepecki Studies conducted in the past few years within the framework of our NCN-funded project allowed us to identify a morphogenetic system of glacial floods in north-eastern Poland, which consists of two principal parts. One (subglacial) comprises a group of subglacial valleys, along with an extensive depression considered as the floodwater source. The other (proglacial) consists of two valleys that come together near the town of Suwałki and form a wide outwash plain further to the south. Our studies of sediments and the conditions of their deposition allowed us to identify, for the first time on the European lowland, landforms that suggest glacial flooding during the last glaciation, including bedforms such as transverse furrows, cyclic steps, scours and small-scale pendant bars and chute bars. One of the most characteristic landforms left behind by the glacial megafloods that have been identified during our research in the Suwałki region are the megadunes identified in the area of Lake Wigry and Lake Serwy. These landforms were studied to identify their morphologic types and estimate paleo-hydraulic parameters, determine the features of the sedimentary environment in different zones of the glacial floodway, the spatial and temporal variation in the deposition of different sediment types and their ages (OSL dating). Among our most important achievements was the identification of a potential source of the glacial floodwaters in the Suwałki region: a subglacial lake situated in Lithuania, where we identified its sediments lying under till layer correlated with the Pomeranian phase of the last glaciation. Having estimated the spatial extent of the lake, we were able to reconstruct water flows under subglacial conditions and in the forefield of the ice sheet. In order to model their dynamics, we used geoinformatics techniques and HEC-RAS software. Our simulations confirmed the location of the subglacial reservoir that served as the source of the glacial megafloods in question, caused by floodwaters flowing out of three different glacier gates (ice portals), and allowed us to calculate their flow hydrograms in the proglacial zone.

Our geomorphological and sedimentological results have already been published in several JCR-listed journals, as well as in a chapter of a monograph published by Springer Nature. Data on the landforms, deposits and processes associated with glacial flows of up to 2 mln m3/s that we identified place our research among the best in the world and shed new light on glacial phenomena in north-eastern Poland and western Lithuania which, as it turns out, had a fundamental impact on the evolution of the valley system in the European Lowland. Our research has won numerous accolades, including a “GEOLOGIA 2021” Award in the “Research record/Fundamental discovery” category of a competition organised by the Ministry of Climate and Environment.

Ice sheet meltwater discharge area near Bachanów, photo Piotr Weckwerth

Every year, over 2 million women around the world develop breast cancer, which is the cause of death in a third of them. Since the most important cause of the high mortality rate of this cancer is late diagnosis, screening tests have been introduced in many countries based primarily on imaging methods that have several weaknesses regarding diagnostic precision. Thus, new methods are being sought to enable reliable detection of changes occurring in the body at the earliest possible stage of cancer development. The source of potential breast cancer biomarkers are components of body fluids, including a diverse group of metabolites. The composition and concentration of these small molecules present in the blood integrate information about all biological processes, thus reflecting the current state of the body.

Dr Karol Andrzej Jelonek, photo by Michał Łepecki The subject of this Project was to characterise the metabolic profile of blood serum in women at increased risk of breast cancer and the signature specific to patients diagnosed with breast cancer. The analyses used material collected from healthy participants of the Norwegian population-based study conducted in 1995-1997 in the Trøndelag region (HUNT2 study), some of whom were diagnosed with cancer during the 15-year observation period, and samples of women with cancer and healthy volunteers from the collection of the Center for Translational Research and Molecular Biology of Cancer. The serum metabolite profile was quantitatively analysed by mass spectrometry using the commercial Absolute IDQ p400 HR kit, which allows for the detection of over 400 metabolites and isomeric groups of lipids.

As a result of the study, several interesting results were obtained. It was noticed that the age of donors is an important factor in changing the concentration of metabolites, therefore research should be conducted on groups with a small age range, ensuring a similar age structure of the compared groups. It was found that reduced serum lipid and amino acid concentrations are associated with an increased risk of breast cancer in a group of healthy women. Unfortunately, the lack of a universal pattern of changes (common to different age groups) and the low statistical power of the differences did not permit the proposal of a metabolic risk signature. It has been shown that reduced levels of most amino acids (except Arg and Gln), ceramides, glycerides, and lysophosphatidylcholines, as well as increased concentrations of hexoses and acylcarnitines are characteristic features of the serum metabolome of breast cancer patients. Additionally, it was found that the set of metabolites that distinguished healthy people from breast cancer patients included molecules that were part of the hypothetical universal cancer signature characteristic of many solid tumours.

Read more on SEMPRA Project website.

Dr Karol Andrzej Jelonek with his team: Katarzyna Morowiec (on the left) and Lucyna Ponge (on the right), photo by Michał Łepecki

The main objective of the DivGene project is to widen our knowledge on plant diseases and the factors influencing resistance or susceptibility to pathogens. The research object is potato, the fourth most important cultivated plant in the world, and its most important disease, economically, potato late blight. This is a disease which attacks potatoes and tomatoes wherever they are grown and which in suitable conditions, at high humidity and moderate temperature, can cause yield losses up to 100%. There is a lack of potato cultivars resistant to late blight that could minimise chemical protection of the plantations. One of the reasons for this lack is the fast evolution of the pathogen that causes late blight. It is a fungus-like organism which spread around the world from America, following the potato. Its strong adaptation potential means that soon after the introduction of a new variety of resistant potato, new pathogen strains appear and spread, able to overcome the resistance and successfully infect the new cultivar.

Prof. Jadwiga Śliwka, photo by Michał Łepecki Recently, DNA sequences of ca. 20 major resistance genes against potato late blight have been elucidated and ca. 60 of such genes have been identified and mapped in potato and its wild relatives. However, we do not know which of the known resistance genes are present in the currently grown cultivars, especially since the resistance of many of them has been overcome. The first specific objective of the DivGene project is diagnosing the presence of several late blight resistance genes and analysis of their diversity in potato cultivars grown in Poland and Norway. The products of resistance genes work as alarm switches that recognise the pathogen’s proteins and start defensive reactions that result in resistance. We know of only 10 cases in which late blight proteins are recognised by the potato resistance proteins. They all belong to the family of effectors with a characteristic RxLR motive. A second project objective is diversity analysis of the genes encoding late blight effectors in the populations of the pathogen in Poland and Norway. These two goals are being achieved with the use of a high throughput next generation sequencing method and a technique that allows for selective sequencing of the genes of interest (AmpSeq). This approach allows us to obtain data on the diversity of the genes crucial for the interaction between potato and late blight in a population scale that was impossible hitherto. A significant advantage of the Polish-Norwegian cooperation within the project is that we obtain data from two different environments, which is used for stronger verification of the hypothesis that the diversity of plant resistance genes and the genes encoding pathogen’s effectors shape the co-evolution of the plant-microbe pathosystem.

Prof. Jadwiga Śliwka, photo by Michał Łepecki Phenotypic validations of the results of the 1) potato and 2) pathogen gene diversity analyses, based on the AmpSeq method, are the next two objectives of the DivGene project. In phytopathological tests, using plants differing by their resistance gene contents and pathogen isolates with defined abilities to cause disease, we confirm both the virulence of the investigated pathogen isolates with different effector variants, and the resistance of potato cultivars with different variants of the resistance genes. We also measure the expression of the studied genes during the disease development to confirm their actual involvement in the interaction.

The expected effect of the project is new knowledge on plant-pathogen interactions and the most important genes involved in it, illustrated by the model example of the potato-late blight pathosystem. This knowledge will help us to answer such questions as: why the plant’s resistance is not durable, whether the durability of resistance conferred by different genes can also be different, what shapes the late blight pathogen populations and why some strains started to dominate them in Poland and Norway. Better understanding of the interactions between plants and pathogens can in future be exploited in practical plant breeding and in improvement of disease control methods, which will help to reduce pesticide usage and the negative impact of the agriculture on the natural environment.

Prof. Jadwiga Śliwka, photo by Michał Łepecki