Projects

Background

Animal use for scientific purposes is guided by the principles of 3Rs (Reduction, Refinement and Replacement). Developing refined experimental conditions can substantially improve animal welfare and importantly, enhance the translational value and data reproducibility.

Novel and emerging technologies allow 24/7 collection of behavioural data in undisturbed mice, the most widely used species in biomedical research. These recently developed technologies minimize the impact of stressors, such as human interaction and testing in novel arenas, which are known to influence data collection and animal welfare. It is now possible to assess a more naturalistic behavioural profile in familiar environment, such as the animals’ home-cage. In addition to promoting welfare, it can improve research in a wide spectrum of research fields ranging from psychology and neuroscience to translational psychiatry and neurology, and may further provide valuable insights into other types of pathologies and genetic alterations. However, addressing the complex problem of monitoring the full 24-hour behavioural repertoire of a rodent still presents many challenges, with each technology having its strengths and limitations.

The aim of this Action is to bring together European organizations developing and using automated home-cage monitoring technologies, combining experts in mouse behaviour, laboratory animal science and data science, to critically and transparently assess the potential of these technologies, to develop user guidelines and standard operating procedures and to identify needs for further technological development, including analysis of big data.

The Action will also contribute to building capacities for adoption of these technologies by holding workshops, laboratory rotations and disseminating knowledge.

Background

Trabecular bone tissue can be properly modeled as an elasto‑visco‑plastic material. However, loading-unloading experiments of individual trabeculae revealed a decrease of the elastic modulus with increasing strain. As such, goal of the current study is to scale the elastic part of a previously developed 2-layer elasto‑visco‑plastic rheological model with a damage variable (from 0-1), which is dependent on plastic strain. This adaptation will enable an improved description of bone tissue material properties. Additionally, new tensile tests will be performed on cortical bone specimens obtained from the shaft of human femurs to compare the usage of the proposed model for cortical and trabecular bone tissue. Additional specimens will be obtained from the femoral neck of healthy and osteoporotic donors to determine if there is a change of material properties of bone tissue with respect to osteoporosis. Previously, it has been shown that there is no significant change of the material properties of individual trabeculae in osteoporosis. Goal of the current study is to investigate if that holds also for cortical bone tissue in the femoral neck. Knowledge of this information is not only essential in computer simulations, which require reliable material input parameters, but also for a better understanding of the effect of osteoporosis on the material itself.

Background

Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway
is frequently associated with tumor development and the constitutive activation of STATs lies at the root of different
hematopoietic malignancies. While several STAT members have been described to act as oncogenes, the transcription
factor STAT3 serves as paradigm for tumorigenic signaling within this family. STAT3 has been described to promote
proliferation as well as differentiation and it is the loss of transcriptional targets associated with differentiation, which is
linked to the acquisition of tumorigenic potential.
The goal of this project is to analyze the contribution of STAT3 isoforms to hematopoietic disorders. We plan to
investigate how the shorter isoform, STAT3β, acts as tumor suppressor during acute myeloid leukemia,
myelodysplastic syndrome as well as multiple myeloma. Furthermore, we aim to elucidate whether the balance of the
two isoforms may help to predict patient outcome. This study is expected to shed light on the function of the shorter
isoform STAT3β and STAT3-mediated control of leukocytes.

Background

Diabetes mellitus is one of the four priority non-communicable diseases worldwide. Globally, 425 million adults suffered
from diabetes mellitus (7.2-11.3%) in 2017 and the International Diabetes Federation estimates an increase of 48% of
the prevalence until 2045. Type 2 diabetes, which is the most common type of diabetes, is mainly seen in adults older
than 40 years. Diabetes can lead to serious long-term complications as well as a lower quality of life, worse mental
health and a reduced life expectancy. These health consequences produce significant health care costs. Due to the
chronical character of diabetes, the disease requires continuous therapy, regular medical appointments and a good
adherence of those suffering. Therefore, diabetes self-management education (DSME) plays a significant role to
increase patient’s self-management capacity and improve diabetes therapy. Research indicates that these outcomes
might be difficult to maintain and seem to decline soon after DSME ends. Consequently, effective strategies to preserve
the positive effects of DSME are needed. Preliminary results show that peer support, which means support from a
person who has experiential knowledge of a specific behaviour or stressor and similar characteristics as the target
population, is associated with better outcomes in terms of HbA1c, cardiovascular disease risk factors or self-efficacy at
lower cost compared to standard therapy. Although those results are promising, research on peer support in diabetes
care is still in its infancy and the influence of various factors is unclear. Peer support instant messaging services (IMS)
approaches have significant potential for diabetes management because support can be provided easily and prompt, is
inexpensive and needs less effort to attend compared to standard therapy. Furthermore, almost half of the 40-69 year
old age group, which is mostly affected by the onset of type 2 diabetes, use IMS.
Aim
The major objective of the project is to analyse the impact of a peer supported IMS intervention in addition to a
standard diabetes therapy on the glycaemic control of type 2 diabetic patients.
Methods
A total of 198 participants with type 2 diabetes mellitus, older than 40 years, and insured by the Insurance Company for
Railways and Mining will be included and randomly assigned to intervention or control group. Both groups will receive
standard therapy, but the intervention group will use the peer support IMS tool, additionally. The duration of the
intervention will last for seven months, followed by an follow-up of seven months. Biochemical, behavioural and
psychosocial parameters will be measured before, in the middle, and after the intervention as well as after the
follow-up.

Background

Ältere Menschen gelten als Risikogruppe der Covid-19-Pandemie und viele der aktuell getroffenen Maß-nahmen wie Social Distancing werden zum Schutz dieser Bevölkerungsgruppe getroffen. Gesellschaftspoli-tisch und wissenschaftlich höchst relevant ist die Frage, welche Auswirkungen Covid-19 auf die psychische Vulnerabilität, die sozialen Beziehungen und den Alltag der älteren Menschen hat. Wie verändern sich die familialen Generationenbeziehungen? Steigt bspw. das Gefühl der Einsamkeit bzw. durch welche (Schutz-) Faktoren (u.a. IKT) lässt sich dieses hintanhalten? Wie verändern sich das Einkaufsverhalten und die Frei-zeitgestaltung und gibt es Unterschiede nach sozialer Lage? Wie wird die Selbstwirksamkeit, dh. das Ge-fühl „Gebraucht-zu-Werden“ beeinflusst? Reagieren ältere Frauen anders als ältere Männer? In Beantwor-tung dieser Fragen kann durch die geplante Studie nicht nur der aktuelle Ist-Zustand älterer Menschen nachgezeichnet, sondern können in der Identifikation von Problembereichen und Risikogruppen Maßnah-men für zukünftige Ereignisse entwickelt werden.

Background

Vibrio cholerae is a natural inhabitant of aquatic ecosystems and the causative agent of the devastating disease cholera. Cholera is caused by toxigenic strains belonging to the serogroups O1 and O139. However nontoxigenic V.cholerae (NTVC) cause several other kinds of infections with potential fatal outcome. In the past 20 years, NTVC infections have been significantly increasing in Europe in association with global warming. In Lower Austria, two extreme cases occurred for the first time in 2015. Both cases were associated with bathing activities during an extreme summer heatwave. To date, the decisive factors controlling NTVC occurrence in inland bathing waters are not clear.
Such information and the availability of reliable NTVC quantification methods are prerequisite to enable prediction models and early warning systems of NTVC occurrence. Besides cultivation on microbiological media, molecular and cell-based methods have been developed. So far, cell-based detection combining fluorescence labelling (FISH) and solid phase cytometry (SPC) proved most successful for NTVC quantification. However, FISH/SPC does not differentiate V.cholerae from closely related species, and it is extremely labor intensive and expensive. In this project, an approach based on alternative molecular recognition molecules –APTAMERS– are proposed. Aptamers are short oligonucleotides that bind their target with high selectivity and affinity. They have proven equally efficient as antibodies in many applications. Once an aptamer is identified, unlimited amounts can be produced at low costs. To date, however, there are no aptamers available for V.cholerae.
Two main goals shall be achieved. First, NTVC abundance shall be comprehensively monitored with state-of-the-art methods along environmental and spatiotemporal gradients in representative bathing waters, and second, a new cutting-edge aptamer technology shall be developed for tailored quantification of NTVC and V.cholerae O1/O139. Prediction models of NTVC abundance in bathing waters shall be delivered as tools for risk assessment and easy protocols for culture-independent quantification of V.cholerae. This will significantly contribute to improved disease preparedness and public health concerning NTVC in bathing waters and toxigenic V.cholerae in water resources. The resulting aptamer products, applications and intellectual property may be exploited in follow-up translational projects, in form of spin-off companies or transfer to local third-party enterprises. The proposal is directly contributing to the prioritised research area “Intelligent Indication Systems and Diagnostics” within the recent FTI strategy for Lower Austria. Sustainable collaborations will be stimulated between the project partners within the Interuniversity Cooperation Centre Water & Health, a research centre to pioneer cutting edge water quality research. Thus, the project will contribute in a sustainable manner to the welfare of Lower Austria.

Background

The rise in antimicrobial resistances is a global threat to human health. Apart from hospitals, where multi-resistant bacteria pose an acute problem, the spread of human-derived antibiotic resistant bacteria (ARB) and resistance genes (ARG) from wastewater treatment plants (WWTPs) into river ecosystems is of growing concern as river water is used for a variety of purposes (drinking water production, recreation, irrigation). Although an increasing number of studies have been published in recent years demonstrating the presence of human-derived ARB and ARG in rivers, no comprehensive quantitative concept exists that describes and explains the distribution patterns, and driving factors of human-derived ARB and ARG in these environments. For this project, a new quantitative concept was developed to study the distribution patterns, propagation pathways and driving factors of human-derived ARB and ARG along four rivers in Lower Austria exhibiting gradients in river size, land use, fecal pollution, hospital wastewater and potential co-selection factors. The following hypotheses shall be tested: (1) In water, human-derived ARB and ARG abundances are coupled to the extent of fecal pollution from WWTPs and to the extent of wastewater input from hospitals. This coupling is independent from the longitudinal development of the river. (2) In biofilms, human-derived ARB and ARG abundances can be uncoupled from the extent of fecal pollution and from hospital wastewater input. In the presence of specific ecological selection factors such as metals or pesticides, anamplification of ARB and ARG occurs. The new concept is based on the quantification of human-derived ARB and ARG in specific bacterial targets, determined in water and biofilms by a combined cultivation and DNA-based approach. This information will be linked with quantitative data on the extent and sources of fecal pollution (following the human wastewater path) and with a comprehensive assessment of the environmental conditions. This study will stimulate new ideas to understand and manage microbial water quality and antibiotic resistance in rivers.
At the global level, the proposal is directly addressing the fundamental requirements of the research agenda defined for water, sanitation and antimicrobial resistance (AMR) of the WHO Global Action Plan for AMR. At the European level it directly addresses the concrete action plan to close knowledge gaps on AMR within the EU AMR Action Plan. At the local level, it directly contributes to the prioritised research area “Organic trace substances” within the “Water” topic of the recent FTI strategy for Lower Austria. Sustainable collaborations will be stimulated between the project partners of the ICC Water & Health at KL Krems, of the department IFA-Tulln of the University of Natural Resources and Life Sciences, Vienna and of the Medical University Graz. By this, the project will contribute in a sustainable manner to the welfare of Lower Austria and beyond.

Background

A postsurgical treatment after ACL reconstruction is necessary for early return-to-sport as well as to minimize the occurrence of long-term complications. However, the required amount of postsurgical physiotherapeutic supervision remains unclear, as studies concerning less supervision (home-based program) showed sufficient clinical outcomes in home-based groups. Gait plays a major role in rehabilitation process, therefore affordable and simple applicable devices are needed for clinical practice, as 3D gait analysis (gold standard) is expensive. Wearable systems like IMUs (Inertial Measurement Unit) are already used for clinical investigation. Still, there is a lack of appropriate methods and scores for gait assessment, concerning rehabilitation after ACL reconstruction. The aim of the current study is the gait-based assessment of the early rehabilitation progress after ACLre construction.
For this purpose, a specific ACL rehabilitation score is developed, including multiple aspects of gait as well as clinical parameters. The quality of the score derived by data of a simple, clinically applicable, IMU-based gait analysis device (G-Walk) is evaluated in comparison to a standard 3D gait analysis system. Based on the developed score, the outcome of two different ACL rehabilitation programs (home-based versus standardized) will be determined. Therefore, a clinical study is conducted. Two groups of patients with different postsurgical treatment after ACL reconstruction will be formed. Gait assessments will be carried out 6-7 weeks, 9-10 weeks and 12-13 weeks postsurgical using a simple IMU-based gait analysis system (G-Walk) as well as standard 3D gait analysis system for validation purpose. Pre-existing gait data of healthy people will serve as a control. A new ACL habilitation score will be developed, including clinical parameters (e.g. range of motion, IKDC, Lysholm), standard gait parameters (regarding kinematics, kinetics and spatiotemporal characteristics) as well as more sophisticated gait parameters like symmetry, variability, complexity or local stability. Statistical analysis will be performed to determine the influence of the rehabilitation programs and the adequacy of the score determined from IMU data compared to 3D gait analysis data. The results of the proposed study will not only give information about the impact of physiotherapeutic supervision on the early normalization of gait and if home-based programs can confidently be recommended for specific patients. It will also provide a clinically applicable method for gait assessment which can be integrated in the routinely follow-up procedure after ACL reconstruction and used to answer related scientific questions. Furthermore, the proposed method can lay the basis for the development of similar scores in different fields of rehabilitation or therapy assessment.

Background

Allergic disease is a clinical and societal burden in Lower Austria and elsewhere. Severe food allergy can manifest as anaphylactic reaction with potentially fatal outcome. IgE-mediated food allergy in children is increasing, affecting 3-8% of under 4 year olds, with peanut as most common specificity. IgE-producing B-cells and IgE-primed mast cells are critical to TH2 driven, Type I hypersensitivity allergic reactions, but the full scope of altered immunity in these patients and the basis for oral immunotherapy efficacy are unknown, particularly in the solid tissues of the human body.
Here, we propose to analyze the cellular organization of the human immune system in health and allergic disease. Our interdisciplinary consortium consists of Dr. Danzl (IST) providing optical imaging, Dr. Boyd (Stanford) contributing immunology expertise, and clinical partners Dr. Maieron and Dr. Sprinzl (St. Pölten) providing human patient tissue biopsies to link our scientific findings to the clinic.
We will further develop imaging technology to characterize transcriptional profiles of single cells in native tissue context. This identifies cell types, subtypes, and activation states, as well as their spatial arrangements and interactions. We will define molecularly-informed cellular microenvironments or “tissue niches” by detecting hundreds to thousands of different mRNAs in highly multiplex single-molecule RNA fluorescence in situ hybridization. We will also develop multiplex protein imaging, with the same goal of decoding patterns of spatial relationships.
We will verify detection of known spatial organization features in human tonsils and Peyer’s patches. We will then extract novel information by defining cell type specific “interactomes” and specific microenvironments or niches based on detailed molecular and spatial information in our multiplex imaging.
We then focus on gastrointestinal (GI) mucosa-associated immune cells and characterize microenvironments of lymphocytes and effector cells. We emphasize IgE-producing B-cells/plasma cells, and evaluate how their microenvironments differ from those of B-cells and plasma cells producing other antibody isotypes, such as IgA or IgG4. The latter may serve a protective role against allergic disease.
We translate these scientific questions to the clinic by multiplex analysis of patient GI biopsies from a Stanford peanut allergy immunotherapy trial. We hypothesize that not only abundance and location of specific isotype-producing B-cells are shifted in allergy but that specific microenvironments act as major drivers of disease and therapeutic responses.
Multiplex single cell analysis of GI biopsies of the same patients pre and post oral immunotherapy will identify therapy-related changes in cellular composition, phenotype, and tissue architecture. We propose to define
multi-parameter, spatially informed biopsy biomarkers predictive of treatment response as basis for a personalized medicine approach to immunotherapy.

Background

Bone is a fascinating, living, and smart load-bearing tissue. It supports the body, facilitates locomotion and acts as protector to inner organs. Understanding of bone mechanical properties helps in developing treatments and clinical applications suitable for more complex and personalized solutions.
In general, biological tissues are inhomogeneous and anisotropic. To understand mechanical behaviour of biological tissues, a complete description of this behaviour over the whole geometry and shape of the sample is necessary. Bone and soft tissues mechanical properties have been widely investigated with different approaches, such as in vitro experiments and numerical models. Experimentally, strain gauges (SGs) are considered as gold-standard for strain measurements on the bone surface due to their high accuracy. However, measurements with the SGs allow only for discrete points to be evaluated and do not provide full-field strain distribution on the surface of the sample. In addition, SGs require detailed surface preparation. A poor preparation can result in extremely inaccurate results. Transducers and extensometers have been used as well to measure the global strain in bone. All the previous three strain measurement techniques induce perturbation in the results due to their contribution to the load-bearing capacity, lead into a systematic underestimate of the actual strain distribution.
During the last years, optical measurement techniques based on digital image correlation (DIC) paired with computational power allowed contactless measurement of whole surfaces. Thus, they overcome the limitation of contacting the surface and availability of single measurement points.
DIC depend on tracking the displacement of recognized features (speckles) on the sample surface. DIC tracks the displacement between deformed and un-deformed digital images of the surface. Based on the digital images, a full-field displacement map is calculated from which a full-field strain map is derived. The accuracy of DIC depends on the quality of the speckles, measurement conditions (light and speckle size and distribution), as well as various software (facet and grid size) and hardware parameters (optics and camera resolution), which must be optimized. Despite the versatile advantages of DIC approach in obtaining full-field strain measurements on the surface of interest, DIC has not been fully exploited yet for measurements on biological samples, and in particular, on bone.
The aims of this study are: (i) extensively investigate the accuracy and precision of the DIC method based on standardized metallic and polymeric samples under zero-load by evaluating the speckle pattern size and distribution, (ii) validation of the accuracy and precision of DIC measuring system against a precise extensometer; (iii) evaluate 3D full-field strain distribution on the surface of biological tissue like bone and tendon samples; (iv) provide practical guidelines on how to harness the benefits of DIC application to measure strain fields on biological hard and soft tissues.

Background

In modern orthopedic surgery, the complication rate due to bone screw breakout and loosening during the convalescence period is still substantial. The surgeon's decision, whether an implanted screw will bear the occurring loads or not, is mainly based on the personal- or clinical experiences. This research project aims to improve the current situation by developing a computer based method which is able to estimate the failure risk of a bone screw prior its implantation. In particular it is hypothesized that the (multi-axial) failure load of an individual bone screw can be predicted by local morphological parameters at its implantation position. This morphological information is based on computer tomography (CT) scans of the fractured bone. In a mid-term perspective, this morphologically-based screw failure criterion could find its way into pre-operative computer planning tools to be used by surgeons for determining the optimal implant position and screw number in advance. Such a clinical tool could lead to more successful surgeries, less costly complications, and higher quality of life for the patient. For developing this screw failure criterion, the idea of bone biopsies studies is followed. A high number of bone samples with screws will be prepared in the laboratory and scanned with a micro-CT system in order measure the local bone morphology. Biomechanical testing in multiple directions will provide data about the mechanical competence of the bone screws including the relevant failure mechanisms. The obtained screws’ failure loads will be related to the samples’ histomorphometric parameters and expressed in a failure surface. With that failure surface, the failure risk of a bone screw can be predicted based on local bone morphology and a loading state prior implantation. In this study standard titanium screws as well as screws made from biodegradable magnesium will be evaluated. This magnesium alloy degrades naturally in the environment of a living body and could make the extraction of implants obsolete. To gain deeper knowledge about that promising material, the failure loads of magnesium screws at multiple degradation states will be compared with standard titanium screws.

Background

In recent months, various media and the population have repeatedly speculated that the Danube navigation would lead to a significant fecal burden on the Danube. However, there are no current and secured data series on the level of fecal pollution over a representative period. The research concept is based on the spatio-temporal high-resolution analysis of fecal indicator bacteria (FIB) for the Lower Austrian section of the Danube, as well as a first assessment of the FIB emission potentials for the Danube navigation with a comparison to municipal sources. In addition, a basic chemo-physical characterization of the water quality and a genetic analysis to determine the sources of fecal pollution for selected locations will be made. Along the Lower Austrian Danube, 11 selected transects (cross sections) will be characterized during the course of the year. In addition, high-resolution time series at neuralgic Danube sites will be surveyed using automated sampling technology. In order to support an estimation of the emission potential of Danube navigation, also waster water sampled directly from the vessels will be examined. All common types of ships or sewage are considered. The study will be carried out in close cooperation between the State of Lower Austria (Gruppe Wasser) and the Karl Landsteiner Private University for Health Sciences, Department of Water Quality and Health, with the support of the ICC Water & Health as partner.

Background

We all know diaries. They are used to record, capture, and monitor our everyday experiences in our own words and are habitually kept on a daily basis. But diaries are also used in science in order to systematically assess life experiences, mostly in a structured form (closed questions) referring to a specific topic (e.g., well-being). Participants may not just answer questions at the end of the day, but also at any time during the day (so-called event- and time-based sampling). In the past, these scientific diaries were used in printed form. However, due to technical progress, nowadays diaries are also digital, and come in new forms and shapes such as Personal Digital Assistants (also known as PDAs) and smartphones. An even more recent development offers further potential as a technological platform for diary studies – wearables. Currently, wearables are predominantly used in sports to measure heart rate and blood pressure, as a pedometer, or to determine the exact GPS position. Meanwhile, the potential to use wearables for scientific purposes, e.g., data collection in diary studies seems substantial. Wearables offer various major advantages, such as being unobtrusive (important for the direct measurement of sensitive topics), not disturbing our daily routines (important for very frequent daily measurements), and being capable of running autonomously (i.e., independent from smartphones and Internet connections). This being said, the present project sets out to develop an open-source software for scientific purposes which should be easily adaptable (e.g., through further sensors, buttons) and work autonomously while implementing low power consumption and the option to store data locally altogether based on a freely available development board.

Background

Pseudomonas aeruginosa is a high-risk bacterial pathogen. Therefore, rapid detection and further identification are important targets in medicine, food industry and drinking water hygiene to ensure public health and safety. P. aeruginosa is a widely spread soil and water bacterium and is regarded as a major hospital germ. Infections with P. aeruginosa are a common cause of morbidity and mortality worldwide. Current methods for detection are often based on classical cultivation, microscopic and biochemical analyzes, and also molecular methods are increasingly used. However, all of these procedures are often time-consuming, expensive, require special equipment and trained personnel. An electrochemical methodology for a Pseudomonas detector is to be developed in the planned NFB project. This biosensor can facilitate the detection of P. aeruginosa as a "pretester" and as an early warning system accelerate the
overall diagnosis of this bacterial pathogen. In the cultivation of the bacterium on cetrimide agar, the release of pyocyanin, a blue-green secondary metabolite, which is specifically produced by P. aeruginosa, results in colored colonies. However, pyocyanine also has redox-active properties and, therefore, can be used for a specific, electrochemical detection of these bacteria. The electroactive properties of pyocyanine can be determined with different voltametric and amperometric methods, e.g. cyclic voltammetry. This bacterial secondary metabolite serves as a starting point for the development of methods, which is carried out at the Danube University Krems, Center for Integrated Sensor Systems, Working Group "Water and Environmental Sensors". The developed procedure is then to be tested with hospital samples from the Clinic Institute for Hygiene and Microbiology, University Hospital St. Pölten. Finally, the results obtained from the detected infection exciter are to be evaluated by the novel sensor and the validated hospital analysis.

Background

Background:
Iron is an essential trace element that is required by all cells, but toxic when present in excess. Iron deficiency is the most common form of micronutritional deficiency worldwide. Preterm infants as well as pregnant women are most likely to suffer from it. During pregnancy, the placenta is the major interface of nutritional exchange between mother and developing fetus. Although mammalian iron metabolism is in general very well characterized, surprisingly little is known about iron metabolism and transfer in the human placenta.
Aims:
Inspired by the substantial gaps of knowledge on human placental iron metabolism and by our preliminary data on human placenta, we aim to study:
(1) The iron metabolism and transport in human placentas and appropriate cell models.
(2) The iron status of healthy mother-child-pairs in relation to placental expression of proteins involved in iron metabolism as well as in relation to placental iron.
Methods:
In the proposed study, which is based on overall 105 healthy, non-anemic mother-child-pairs, iron status of pregnant women and neonates in relation to placental expression and localization of iron metabolising and transporting proteins is investigated. In vitro experiments with human placental cells (primary trophoblast cells, Hofbauer cells, primary placental endothelial cells, and the two placental cell lines BeWo and HUVEC) will be conducted to examine and confirm the involvement of TFR1, FPN1, ZIP8 and other (to be selected) candidate proteins in placental iron metabolism and transport.
Innovation:
The proposed study is the first, which combines iron status of mother-child-pairs with extensive basic research (protein expression, function, and localization) on human placentas. The key proteins involved in human placental iron metabolism and transport will be examined for the first time together. The study is based on a comparably large number of mother-child-pairs. With the proposed study we aim to add new knowledge on human placental iron metabolism and transfer. We expect long-term benefits arising from this innovative approach, which will enable us in the long run to optimize the therapy of maternal and preterm iron deficiency.

Background

The discovery of the more than 30,000 years old ritual double burial of two neonates at the Krems-Wachtberg site in 2005 has evoked much attention not only by the media and the general public, but also from the international scientific community as findings of sub adults of ancient humans are, on a global scale, extremely rare occasions. After the discovery and exposure the ritual burial was carefully recovered as a block, and the fragile specimens were stored to keep its original excellent condition. In 2015 the recovered block was excavated, documenting each single step with state-of-the art methods.
Digitisation is now aimed for to enable analyses, restoration and also visualisation. Currently, the only non-destructive way to make a digital copy and visualize the remains is high-resolution micro-computed tomography imaging. It allows 3D reconstruction of the surface as well as the inner micro-structure - making it possible to “uncover the invisible”. Such a device has been installed at the division for Biomechanics of KL University as part of the Core Facility at Campus Krems. This will overcome the current restrictions of analysis and allows a digitisation of the findings for future analysis.
Together with the available light scanning data from the excavation the whole assembly can be reconstructed. Apart from 3-dimensional reconstruction it will be possible to restorate the chaîne operatoire of activities which were part of this burial process, as well as the post-sedimentary formation processes (4D = modelling the development through time).
In addition to the reconstruction of the burial, up-to-date documentation and archiving of the data is of utmost importance to lay a basis for further research. Thus, one of the main objectives of this pilot project is to set up a catalogue of criteria for a long term, open-source data repository which provides access to all the data regarding the excavation and findings for larger groups of scientists beyond disciplinary borders.
Digitisation of the Krems-Wachtberg double burial is challenging in all respects and requires a variety of experts to deal with the many aspects that are inherent in such a spectacular discovery. For the first time, it is possible to investigate this outstanding find from Krems-Wachtberg under the leadership of Lower Austrian research institutions. As one of its main targets, the proposed project will contribute to a further professionalization in Collection Management and Museology – one of the areas of Lower Austrian FTI strategy – and it will significantly improve the visibility of cultural heritage in Lower Austria by latest technical developments that allow for scientific exploitation on an international level.

Background

Dieses Projekt wird aus Mitteln des Europäischen Fonds für regionale Entwicklung (EFRE) kofinanziert. Nähere Informationen zu IWB/EFRE finden Sie auf www.efre.gv.at
Microenvironment-induced signaling pathways regulate the activity of numerous transcription factors (TFs). Approaches to target TFs are among the most promising novel anticancer strategies with a potentially high therapeutic index. Our recent data indicated a key role for the AP-1 family member JunB in MM pathogenesis (Fan et al., Leukemia 2017). In continuation of these findings, the proposed project aims to further define JunB as a novel therapeutic target in MM, and to thereby set the pace for the development of direct or indirect JunB inhibitors in order to further improve patient outcome.

Background

Rare earths are used in electronic devices such as mobile phones, computers and energy-saving bulbs. However, they are scarce and cannot be recycled using eco-friendly methods. Complex and expensive mining, coupled with scarce supply, means that the prices of rare earths on the world market are rising steadily. Due to continuous technical advances, we can already predict that the supply situation for rare earths will become critical in future, which in turn could pose a threat to the development of innovative technologies.

The project partners aim to counter this trend using a new technology. This involves an approach that has never been used before: recycling by means of microorganisms (bacteria and algae). The goal of the international project partner consortium is to develop a practicable recycling technology in collaboration with regional industry, with a view to reclaiming rare earths from electronic waste and subsequently making the technology available to businesses. The consortium liaises regularly with its strategic partners, which guarantees that market needs and the technological limitations of business are taken into account in the development process.

Background

Patients being treated frequently and in different care facilities, also due to repeated treatment discontinuations, burden the care structures. The causes of the repeated treatment discontinuations and consequently readmissions, as well as the lack of reintegration are not restrictive known. It is therefore of great importance to investigate which factors are associated with potential readmissions and play a role in social reintegration. This project examines the benefits of patients with special aftercare needs. The goal is to optimize the graded care and reduce the readmissions. Basic knowledge will be gained on the benefit of patients with special care needs, who will contribute to the dismissal of the care system.
Questions:
1. Are there subgroups of patients with or without fundamental social and cognitive impairment among psychiatric patients with addiction (F1) or personality disorders (F6)?
2. Is there a difference among the subgroups of psychiatric patients with or without cognitive thinking disorders regarding (re)admission r and cumulative length of stay, and social and professional reintegration

Background

3D printing is entering medicine and can help in many ways. In addition to accurately fitting implants and orthoses, 3D printing can be used in surgical preparation to gain a better understanding of the planned surgery. Increasingly, the printing of organs is becoming more important. In this research project materials are to be printed with the help of the Polyjet process which come as close as possible to real biological tissues from the haptic but also with regard to the biomechanical behavior. The printing technology developed in this way enables the production of patient-specific organ models based on CT and MRI data, which can be used for preoperative planning prior to complicated procedures. Furthermore, for the further development of surgical techniques and implants mechanically equivalent organs or specimens can be produced, which make dispensing with the use of body donations for these concerns. The printed organs are standardizable and have no undesirable variability, as is the case with body donation.

Background

For decades virtually every easily cultivable microorganism has been investigated in pharmaceutical highthrough put screens (HTP) for natural bioactive compound production and after observation of a constantly increasing rediscovery rate of bioactive compounds the source was declared empty. As a consequence; large scale screening programs for natural bioactive compounds were mostly terminated. However, in recent years, the interest in natural bioactive compounds has been reignited based on mass sequencing results of microbial genomes predicting a much richer diversity of microbial metabolites than previously anticipated. These so called “cryptic” metabolites hold the potential for novel antibiotics, directly needed for the armsrace against the ever increasing incidence of pathogenic resistance. A promising approach to activate the production of “cryptic” metabolites is co-cultivation of competing microorganisms. For example fungi and bacteria are talented producers of natural compounds with potentially strong bioactive functions. In a previous work we could demonstrate that small chemical effectors induce or increase the production of otherwise repressed compounds in fungi which raises the chance of discovery of novel compounds. In addition it has been demonstrated that biotrophic conditions influence the production of bioactive compounds in fungi. Thus as innovative screening attempt we propose a high throughput assay combining small chemical effector treatment with combinatorial growth of fungi and bacteria under various biotrophic conditions. We will realize an automated HTP pipeline to co-cultivate 144 selected bacterial strains with 32 different fungi using 4 small chemical effectors under 4 biotrophic conditions. The 73728 so produced culture extracts will be screened for their ability to counteract microbial resistance in a direct approach for the presence of novel antibiotic compounds not susceptible to commonly found microbial resistances from human and veterinary sources in Lower Austria. Furthermore, in an indirect screening approach we will generate reporter strains primed for the presence of erm or cfr methylase mediated antibiotic resistance inhibitors. These resistance mechanisms are based on methylation of 16S rRNA which mediates resistance against several antibiotics at the same time and so far no in vivo active inhibitor has been discovered. The proposed project will deliver a co-cultivation HTP pipeline and a highly divers set of HTP assays for target driven screening attempts and has the potential to discover novel bioactive compounds.

Background

Osteoporosis (OP) is a silent bone disease resulting in loss of bone density, decreased bone strength and ultimately fracture. It is underrated, underdiagnosed and undertreated. Every third women and every fifth men over 50 are concerned. OP is responsible for more than 4 million fractures annually in the EU, with hip fracture as the most common type. This translates into more than €40 billions of health care costs, out of which less than 5% is spent on prevention. Beside diabetes, cardiovascular diseases, and cancer it’s one of the important health care challenges in the next decades. Especially in Lower Austria this puts an estimated €200 million of annual burden on the healthcare system only. The early diagnostics of OP is vital for fracture prevention. This in return increases the life quality of the patient, and decreases the healthcare and social costs. Bone density is used as predictor of osteoporotic fracture risk. It is measured with DEXA and diagnosed with a derived T-score. However, recent studies showed the inaccuracy and insufficiency of such densitometry measures. For example, more than 50% of OP fractures occur in the patients who are considered as “low risk” by this method, and 15% of patients are falsely treated for being at "high risk". An improvement of this situation needs (a) better screening techniques, (b) more screening, and (c) improved diagnosis scores. The goal of this project is to improve osteoporosis diagnostic tools. Bone fracture happens because of overloading and/or reduced resistance against loading due to bone loss. Finite element analysis (FEA) simulation is a non-invasive numerical method which is able to estimate individual bone strength in-vivo based on DEXA or Quantitative Computed Tomography (QCT) images. Geometrical, structural, and material properties are computed from images and combined with typical physiological loading conditions including the magnitude, direction, and frequency of the loading. The accuracy of the model is inherited from a good knowledge of all these parameters. FEA -based bone strength has the potential to effectively improve diagnosis, assessment, and monitoring of osteoporosis. But despite the significant progress made in the last decade, these predictions still need considerable improvements through enhancements in imaging, mechanical testing, and simulation techniques to justify their clinical use.

Background

Molecular faecal pollution diagnostics, based on the detection of genetic faecal microbial source tracking (MST) markers, is about to revolutionise water quality testing. Such applications have been mainly focusing within the fields of recreational water quality monitoring, shellfish production, and maximum daily load monitoring. Scientific knowledge on the application of genetic faecal MST marker diagnostics, to support drinking water supply management and water safety planning, is hardly available yet. The proposed translational research project is going to establish the basic scientific knowledge needed to apply and further develop cutting edge genetic faecal marker diagnostics for quality testing to support water safety plans of drinking water supplies of tomorrow. Genetic faecal MST markers are supposed to extend current monitoring practices based on standard faecal indicator bacteria (SFIB) E. coli and enterococci in order to identify potential contamination sources for elimination or minimisation, and, to bridge the gap between traditional faecal pollution monitoring and microbial risk assessment. However, molecular diagnostics with adequate faecal-source specificity and faecal –source sensitivity is considered a key prerequisite for these applications. A new tiered application strategy for drinking water resources monitoring, based on the combination of bacterial and mitochondrial genetic faecal MST markers, is proposed. The new strategy will systematically be evaluated by means of relevant faecal pollution sources,
representative water resources in Lower Austria, and important disinfection processes. To enable comparisons to traditional methods investigations will be complemented by SFIB and total cell count analysis. Chemical markers will be evaluated to support genetic MST diagnostics. The topic “Intelligent Indication Systems and Diagnostics” has been defined as prioritised research area within the recent FTI strategy (Programme for Research, Technology & Innovation for Lower Austria). The submitted research proposal is thus directly contributing to the adopted FTI strategy. The translational research project will stimulate sustainable collaborations between the Karl Landsteiner University, the well-established Center for Analytic Chemistry at IFA Tulln and the Interuniversity Cooperation Centre for Water and Health, a research centre to pioneer cutting edge water quality research. Furthermore, the project will directly collaborate with EVN Wasser GesmbH, the leading Lower Austrian drinking water supplier. The project will thus directly establish links between cutting edge water research and activities of a leading drinking water supplier to support the realization of water safety management of the future. Joint collaboration between these excellent partners in research and management will contribute to a further establishment of Lower Austria as a leading region in the water sector within the Danube and Central European Region.

Background

Therapeutic protein drugs have been widely used to treat a variety of diseases including cancer, autoimmune diseases, neurological diseases, metabolic diseases, bleeding disorders and others. The global protein drug market reached nearly $174.7 billion in 2015 and should reach nearly $248.7 billion by 2020. Although most protein drugs offer a favourable benefit-risk ratio, one key hurdle for the maintenance of clinical efficacy and safety has been the development of unwanted immune responses against protein drugs, in particular the development of anti-drug antibodies. Some patients develop pathogenic antibodies which neutralize the biologic activity of the protein drug or cause devastating health problems such as anaphylaxis or autoimmune pathologies. Currently, there is no diagnostic tool which can predict and distinguish the development of harmless or pathogenic antibodies in an individual patient. Therefore, basic research efforts are required to better understand immune regulation and nature of harmless and pathogenic anti-drug antibodies and to create the scientific basis for the development of novel diagnostics. Early diagnosis of evolving pathogenic antibodies would provide a window of opportunity for early immune intervention which could prevent pathogenic immune responses. One prominent example of pathogenic anti-drug antibodies is the development of neutralizing antibodies against factor VIII (FVIII) following replacement therapy of hemophilia A patients with human FVIII products. The antibodies neutralize the biological activity of FVIII and render replacement therapies ineffective which can result in life-threatening bleeding complications. In this project application, we propose to close a major gap in current understanding of the nature and evolution of pathogenic antibodies against FVIII and their differentiation from non-pathogenic antibodies in patients with severe hemophilia A. We aim to generate novel data on the temporal association between epitope specificity (protein epitopes versus carbohydrate epitopes), affinity, isotype/IgG subclass profiles and functional activities of antibodies against FVIII which develop in patients following replacement therapy with FVIII products. The possibility to combine basic research with the analysis of longitudinal samples obtained from patients undergoing FVIII therapy will provide a unique opportunity to directly translate novel research findings into clinical application. The data coming out of this project will provide the scientific basis for the development of novel diagnostic tools, such as FVIII-specific microarrays, which will allow physicians to differentiate patient-specific characteristics and design personalized treatment approaches, and ultimately improve patient outcomes.

Background

Metastatic spread causes 90% of all tumor related fatalities and thus represents the greatest challenge for cancer patient survival. Tumor cells need to become motile and cross vascular barriers for metastatic spread. How these processes are controlled is not yet fully understood. The laboratory of Dr. Daria Siekhaus has identified a novel transporter, CG8602, required for Drosophila macrophages to invasively migrate into the tissues of the embryonic germband. Data from the Siekhaus lab point towards a role for CG8602 in regulating the glycosylation and stability of proteins that limit tissue entry. CG8602 appears necessary for the increased level of T antigen present on the surface of macrophages invading the tissue of the germband. Intriguingly, increased levels of T antigen have been found in metastatic cancer and antibodies against T antigen can reduce metastasis. This raised our interest in translating our findings into vertebrates, and Dr. Siekhaus recruited a post-doctoral fellow, Dr. Marko Roblek, with extensive experience in studying metastasis in mice back to Austria from Switzerland. This fellowship will help pay for his salary and material costs and thus enable him to conduct the work that will form the foundation for establishing his own independent lab. The mammalian ortholog of the CG8602 transporter, called MFSD1, is highly conserved, and belongs to the solute carrier superfamily (SLC). Yet its functions remain unknown due to a lack of prior studies. We seek to examine the role of MFSD1 in tumor cells during mouse metastatic initiation, We also will examine whether and how MFSD1 is involved in regulating protein glycosylation, protein stability, and how these potential changes affect the regulation of invasive tumor migration. By analyzing the function of MFSD1 and its interaction partners we aim to uncover the mechanism from aberrant glycosylation to the invasive migration phenotype observed during metastatic spread of tumors. This will include analysis of cell surface proteins, signaling cascades, and transcriptional regulation of cell migration. To test the relevance of these findings for the clinic, we are partnering with Dr. Wiesholzer and Dr. Kitzwoegerer at the Clinical Division for Internal Medicine, KLU University St Poelten. By analyzing resected tumor tissue from patients we will determine whether the level or localization of MFSD1 can be correlated with disease prognosis. We are eager to transfer findings from Drosophila to the vertebrate system in the context of metastasis research. Our prior data leads us to believe that this will lead to the description of an evolutionarily conserved mechanism that regulates invasive migration regulation from fly to vertebrates. This work can lay the ground work for
understanding the basic biology of a novel vertebrate gene involved in regulating invasion and metastasis, and thus for the eventual development of a new therapeutic target and diagnostic biomarker for the clinic.

Background

Biomarkers as indicators for therapeutic mode, onset, and response to treatment are rapidly gaining importance in clinical cancer management. Cancer biomarkers are tumour- or patient-related factors, which reflect the biological behaviour of a tumour and thus constitute a prognostic tool. Cutaneous malignant melanoma is a highly aggressive and metastatic tumour arising from cutaneous pigment cells termed melanocytes. Although incidence of melanoma and related mortality are continuously increasing, it is still impossible to predict the metastatic behaviour of melanoma in individual patients.
In the past five years, the field of "liquid biopsies", i.e. the gain of important information on tumour development via nucleic acid (NA)-based analysis of blood samples, has tremendously progressed. It is now evident that in the blood, tumour-cell derived NAs reside in three different compartments, i.e. (i) intracellular NAs in circulating tumour cells, (ii) NAs in extracellular vesicles, and (iii) freely circulating protein-bound DNA in the plasma. Importantly, extracellular NAs are more abundant in blood, and therefore more accessible.Currently, the clinical applicability of blood-based tumour detection and monitoring methods is still limited to patients with progressive (metastatic) disease. Based on the hypothesis that a compartment-specific NA analysis will considerably aid in improving blood test sensitivity in comparison to holistic approaches, the overall objective of the herein presented study is to exploit the compartmentalization of tumour-derived blood NAs in order to establish a novel strategy for highly sensitive blood-based detection and monitoring of early stage human melanoma disease and metastasis. The applicant and cooperation partners aim at achieving this goal by (i) addressing the amount and composition of extracellular vesicular nucleic acids and circulating free DNA in vitro in order to comparatively evaluate vesicles as a reservoir of potential NA-type biomarkers, (ii) addressing the presence and amount of tumour-derived NA per compartment and possible changes of these parameters over time in a clinical study involving late stage melanoma patients, and by (iii) addressing the presence and amount of the most promising tumour-derived NAs identified in (ii) in a clinical study involving patients with high risk of melanoma recurrence as to achieve earliest possible detection of disease recurrence.

Background

Malignant melanoma is the most frequent cause of skin cancer-related deaths. Despite the progress in understanding the biology of this disease, it still remains a significant clinical problem. Melanoma is often associated with activating mutations in the BRAF gene at the amino acid position 600, which results in an uncontrolled activation of the MAP-kinase pathway and - as a consequence - leads to increased cell proliferation and migration. Although several BRAF inhibitors, such as vemurafenib, have been proven to be highly effective in inhibiting BRAFV600 mutated melanomas, resistant-associated secondary mutations, which reactivate alternative survival pathways, often occur. We have recently reported on the response of chondroitin sulfate proteoglycan 4 (CSPG4)-specific Abs to enhance the anti-proliferative effects of vemurafenib. These data implied that the microenvironment is important in determining the effect of targeting CSPG4 on cell migration and invasion and suggest a role for CSPG4 in the phenotypic plasticity of melanoma cells and the emergence of a transient drug-resistant state. Central to the model of stress-induced drug tolerance resulting in multi-drug resistant cancer cells called induced-drug tolerant cells (IDTCs) is their propensity to develop colonies for which cell adhesion is crucial. Based on these findings of cell adhesion and cell motility being crucial for early drug resistance we propose that anti-CSPG4 antibodies, which have shown promising results in two different animal models, prevent or delay IDTC formation in mutant BRAF melanoma cells if combined with standard treatment modalities such as BRAF and MEK inhibitors. During this project we will validate this hypothesis with in vitro and in vivo models of melanoma, we will analyse changes on protein and gene expression levels induced by these treatment modalities and we will validate these experimental data on patients´-derived melanoma samples. Targeting IDTCs with anti-CSPG4 antibodies could be a crucial step for the prevention of acquired drug resistance.

Background

Melanoma is one of the most frequent tumors in young adults and despite it only accounts for 4% of all cases of skin cancer, melanoma is responsible for 79% of all skin cancer related deaths. Despite progress has been achieved in treatment of Melanoma (e.g with B-raf inhibitors), finally patients succumb due to resistance mechanisms acquired by the tumor. Many lines of evidence have shown that especially metastatic melanoma exhibits a strong metabolic turnover, which is needed to fuel cell proliferation and anabolic pathways. This increased cellular turnover also results in an increased demand to maintain the redox homeostasis. Here we propose to analyze this high metabolic and therefore also ROS (Reactive Oxigen Species) generating stress as a possible Achilles heel of melanoma. One of the major regulators of stress response in cancer is NRF2. It plays a central role in protection of cells against oxidative and xenobiotic stresses. Therefore the inhibition of NRF2 or its target genes might re-establish the sensitivity of melanoma to apoptosis driven by ROS. Furthermore this mechanism could prevent resistance mechanisms frequently observed in metastatic melanoma and it might abolish the frequently observed activation of endothelial cells, which surround tumor cells. It is highly likely that a combination of state of the art melanoma treatment with compounds that inhibit the generation of ROS scavengers, potentiates the effectiveness of the current treatment regiments. We will use CRISPR based methods as well as pharmacological inhibition to elucidate the mechanistic role of NRF2 in melanoma cells and on endothelial cells. Furthermore we will transfer knowledge gained from our model by closely cooperating with clinicians, who routinely care for melanoma patients. Concluding, we propose that abolishing the antioxidative response by suppressing NRF2 directly or its targets will be an effective contribution in the battle to fight metastatic melanoma.

Background

Severe deafness (1.7% of the total population) leads to social isolation, disability and early dementia. Hearing aids and cochlear implants (CI) bring help here, but eliminate the socio-economic effects only partially. The reason lies in the failure of the so-called "Cocktail Party Ability", where with a healthy hearing one can focus on a single conversation in a noisy room.
This data processing is not found in the cortex, but the latter actively controls a filtering in the auditory organ (cochlea) via a down-going multilevel, efferent control. Despite all signal processing in hearing aids and CI, this unconscious regulation is difficult to imitate and their regulation by patients remains almost unused because of inconvenience. What is missing is the technical closing of the extended loop consisting of cochlea, cortex and hearing aid / CI.
With Brain Computer Interfaces (BCI), the connection of the cortex or underlying stations of auditory efference to hearing aids could be possible in the future, albeit to a large extent cooperation of audiologists, neurosurgeons, electrophysiologists, electrode developers, modeling neuro- and cognitive scientists is needed. The University Hospital St. Pölten (UKStP) of the Karl Landsteiner Private University for Health Sciences recommends itself as the initiator of a roadmap, which incorporates the state of knowledge into teaching, evaluates the application focus and communicates a consensus on challenges and milestones.
In addition to this long-term approach, in the first, smaller experiments it will be tested if efferent control can work. These experiments as part of ongoing animal experiments and CI patients allow easier access to the efferent auditory system to test (compound action potential CAP, tonotopic action potentials in sensing CI mode and EEG leads). A success would be a tentative conclusion of efferent regulation allowing patients to learn to use the efference - possibly as intuitive as BCI-controlled limbs *. (* Collinger JL et al, J. Clin. Trans. Science (2014) 7, 1, 1752-8062)

Background

Implantable hearing aids are in clinical use since more than 25 years. These include cochlear implants (CI), auditory brainstem implants (ABIs), bone-anchored hearing aids (BAHA) and implantable middle-ear implants (MEI). The main challenge for all these implantable devices is a lack of reliability of the implantable microphone due to a constant decrease of the initial sensitivity after exploitation. In this project we propose a contactless fiber-optic sensing technique based on low-coherence interferometry for amplitude measurement of the hearing ossicles, e.g. incus or malleus. Our approach is physiologically fully justified because sound transmission to the inner ear can be realized without any obstacles, taking advantage of the natural amplification properties of the outer ear and the ear drum. There is no feedback noise and signal distortion due to decoupling the microphone from the actuator. The contactless method does not change the original properties of the acoustic signal at all and the ossicle chain stays intact. The distance of about 5 mm between the sensing fiber and ossicle is large enough to prevent scarring. This also allows to use the device in case of small quasi-static long-term movements of ossicle in the middle-ear, that usually occur during the children growth, or rather large quasi-static short-term movements in case of alternation of atmospheric pressure or chewing. The current prototype of the device can reach sensitivity of about 40db SPL and about 70db SPL in audio frequency range which now should be further improved to around 30 dB SPL by increasing the signal-to-noise-ratio (SNR) of the system, accomplished by noise suppression of some individual parts of the system, like light source, fiber-optic link, photo receiver, or overall sensing configuration. Additionally, a more effective algorithm will be developed and embedded in a low-consumption DSP. The results will be verified by pre-clinical ex-vivo examination