Dr. Ulrike Schimpf

Att övervinna slem: nya antimikrobiella medel och leverans för att behandla slemhinnesinfektioner

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English: Overcoming the mucus: new antimicrobials and delivery to treat mucosal infections

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Summary: This collaborative project will allow the exchange of two Swedish researchers and two Brazilian researchers, between the Royal institute of Technology, KTH (Sweden) and the Federal University of Ceará, UFC (Brazil). These exchanges will allow to expand an ongoing research in both groups on the development of antimicrobial strategies and provide access to material and methodologies otherwise inaccessible to these groups. The overall aim of the research program is to develop new strategies to treat microbial pathogens that are protected by the mucus gel that covers the mucosal epithelium they infect. In the first half of 2022, Dr. Sedef Ilk, from KTH will spend 5 months at UFC to explore the use of a chitosan/lecithin nanoparticle system to load new essential oil antimicrobial compounds. During that time, Dr. Raimunda Sâmia Brilhante Nogueira from UFC will spend 6 months at KTH to learn about mucus and develop a mucus-model to test antimicrobial compounds on pathogens typically infection mucus-covered epithelium in a more relevant fashion. In the second half of 2022, Dr. Ulrike Schimpf from KTH will spend 3 months at UFC to test the new nanoparticle loaded with antimicrobial on clinical relevant strains, leveraging the newly-developed mucus containing model. Finally, Dr. Rodrigo Silveira Vieira from UFC will come 6 months at KTH to modify the nanoparticle system to improve its diffusivity into mucus.

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In cooperation with Assoc. Prof. Sedef Ilk, KTH (Department of Chemistry, Sweden), Dr. Thomas Crouzier, KTH (Department of Chemistry, Sweden), Prof. Rodrigo Silveira Vieira, Federal University of Ceará (UFC, Department of Chemical Engineering, Brazil), Prof. Raimunda Sâmia Nogueira Brilhante, UFC (Department of Pathology and Legal Medicines, Brazil), Prof. Marisa Masumi Beppu, Unicamp (School of Chemical Engineering, Brazil), Prof. Mariana Agostini de Moraes, Federal University of Sao Paulo (Department of Chemical Engineering, Brazil).

A physiological approach of mucus-based sperm selection to improve assisted reproductive treatment success rates

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Summary: We aim to develop a technology that can drastically improve the outcome of Assisted Reproduction Technologies (ART). Since the introduction of ART in the late 1970:ies, the chances for childless couples to become biological parents have drastically increased. Still, on average about 40% of infertile couples undergoing any type of ART treatment are not successful. Present routines for sperm handling in ART treatment may not be completely optimal for the selection of sperm and this in turn leads to lower success rates of treatments. There are studies that suggest that our handling procedures can cause detrimental effects on the sperm potentially lowering their ability to fertilize the oocyte or that the pregnancy is terminated early. In order to overcome these problems of current ART technology, we will explore and develop techniques that better emulate the physiological state and environment that human sperm are exposed to during natural fertilization. We expect to select sperm with better capacity for normal fertilization and embryo development than current sperm preparation techniques thus improving ART outcomes. This will be achieved through 3 main goals. First, development of a method and device to migrate and collect sperm after migration through mucus-filled channel. Then, the development of synthetic materials that closely emulate human ovulatory cervical mucus, and which allow for an affordable scale-up of the system. Third, the validation of the selected sperm in comparison to current sperm selection techniques. This project, combining KTH technical expertise, world-class andrology expertise from SLL and the Karolinska University Hospital, and in close collaboration with Nidacon International AB, a world leader in fertility clinic reagents would maximize the chance of positive impact on fertility clinic patients in the near future.

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In cooperation with Dr. Emma Holmes from the Swedish Nidacon International AB and partners of the Karolinska University Hospital (Sweden): Dr. Lars Björndahl (ANOVA, Andrology, Sexual medicine and Transgender medicine) and Dr. Aino F. Jonasson (Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Obstetrics and Gynecology).

Engineering cervical mucus to reinforce barrier to sperm - Development of a non-hormonal contraceptive (medical device)

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Summary: The aim was to complex ovulatory human cervical mucus by selected polysaccharides to reinforce the mucus and block sperm penetration in the reproductive tract. For in vitro tests, I developed an assay to analyze the sperm penetration through untreated and treated cervical mucus. Subsequently, we analyzed the diffusion of polysaccharides into cervical mucus and selected polymers for sperm penetration assays. Alongside these studies, we focused on the biocompatibility of selected polysaccharides on sperm. Sperm penetration assays revealed polysaccharides of specific molecular weight exhibiting high potential to hinder sperm migration through mucus, under extensive use of ovulatory cervical mucus and semen samples of volunteers. The application of a high number of cervical mucus led further to an evaluation of the cervical mucus assessment and its related sperm penetrability valuation.

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In cooperation with Cirqle Biomedical (Denmark) and partners of the Karolinska University Hospital (Sweden): Dr. Lars Björndahl (ANOVA, Andrology, Sexual medicine and Transgender medicine), Dr. Sebastian Gidlöf (Department of Gynecology and Reproductive Medicine), and Dr. Aino F. Jonasson (Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Obstetrics and Gynecology).

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PATENT: A VAGINAL CONTRACEPTIVE COMPOSITION FOR REINFORCEMENT OF MUCUS BARRIER PROPERTIES (WO2021069046 (A1)) 

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PRODUCT WEBPAGE

Investigations on the anti-fungal potential of molluscs

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Summary: in work

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In cooperation with the German Robert Koch Institute Berlin - Federal Government’s central institution in the field of biomedicine and Institute for Public Health.

Deutsch: Mikronisiertes Kollagen – Gesundheitsfördernde Applikationen von mikrostrukturiertem Kollagen (250 TEUR)

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Teilvorhaben 1: Chemische Vernetzung von löslichem Kollagen zu stabilen Mikrostrukturen  (125 TEUR)

 

English: Micronized Collagen – Health-supporting Applications of Micro-structured Collagen

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Sub-project 1: Chemical cross-linking of soluble collagen to stabile microstructures

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Summary: in work

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In cooperation with the German Fraunhofer Institute of Applied Polymer Research (IAP), Freie Universität Berlin (FU), GfN Herstellung von Naturextrakten GmbH, LIPROMAR GmbH and NanoPET Pharma GmbH.

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Report: https://doi.org/10.2314/KXP:1698145403

Deutsch: Entwicklung von Sensortechnik und Grundlagen einer flexiblen lastabhängigen Steuerung der Intermediatbildung in zweiphasigen Biogas-Prozessen unter Berücksichtigung einer vollständigen Substratausnutzung (1.5 MEUR)

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Teilvorhaben 4: Verwertungsstrategien für Nebenprodukte des zweiphasigen Biogas-Moduls zur Nutzung der Gesamtpflanze (400 TEUR)

 

English: Development of sensor technology and fundamentals of flexible, load-dependent control of intermediate formation in two-pase biogas processes under consideration of the complete substrate utilization

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Sub-project 4: Innovative strategies for the utilization of by-products from a two-phase biogas module for the use of the whole plant

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Summary: in work

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In cooperation with the German Bavarian State Research Institute for Agriculture (LfL), University of Hohenheim (UoH), Goethe Center for Scientific Computing (G-CSC) of the Goethe University Frankfurt/Main and Pilzhof Dr. Schulz.

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Report: https://doi.org/10.2314/GBV:881605212

Deutsch: Entwicklung eines biologisch-technologischen Verfahrens (Prämix) zur nachhaltigen Reduktion von Deoxynivalenol (DON) und anderen Mykotoxinen in kontaminierten Getreide (250 TEUR)

 

English: Development of a biologic-technological process (premix) for sustainable reduction of deoxynivalenol (DON) and further mycotoxins in contaminated cereals

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Summary: in work

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In cooperation with the German PROTEKUM - Umweltinstitut GmbH.

Deutsch: Bioraffinerie-Modul zum gerichtet-fermentativen Aufschluss von Biomasse für eine kombinierte energetische und stoffliche Verwertung (2 MEUR)

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Teilvorhaben 1: Biokatalytischer Aufschluss von NaWaRo (300 TEUR)

 

English: Biorefinery module for the directed, fermentative conversion of biomass for a combined energetic and material utilization

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Sub-project 1: Biocatalytic degradation of renewable raw materials

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Summary: in work

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In cooperation with the German Bavarian State Research Institute for Agriculture (LfL), University of Hohenheim (UoH), Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB), Goethe Center for Scientific Computing (G-CSC) of the Goethe University Frankfurt/Main and Pilzhof Dr. Schulz, Biopract GmbH, Hörmann Energie und Umwelt GmbH and Avat Automation GmbH Tübingen (AVAT).

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Report: https://doi.org/10.2314/GBV:766705102

 

PATENT: ENZYMPRÄPARAT ZUR STABILISIERUNG UND STEIGERUNG DER BIOGASPRODUKTION (DE 20 2010 006 607.7) 

Test trial KTG Biogas AG (plant Putlitz) – Evaluation of the effect of enzyme addition on performance (enzyme sponsored by DSM)

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Summary: During my PhD studies, I found a commercial pectinase preparation produced for fruit processing, outperforming commercial cellulase, hemicellulase and laccase preparations. The enzyme preparation was tested in vitro on diverse substrates and showed overall success in terms of increasing the methane production during anaerobic digestion. To confirm a positive effect on a larger scale, a practical trial was initiated using identical operated, horizontal biogas plants from KTG Agrar SE fed with crops, leading to high dry matter concentrations of the medium. The pectinase preparation was sponsored by DSM. One bioreactor was used as control and was operated without enzyme application. The regime of testing enzymes in the second bioreactor was as follows: a) reference period without enzyme application, feeding maize, grass and corn, b) enzyme application to maize and corn, c) enzyme application to maize, corn and sweet sorghum, d) enzyme application to maize, corn, sweet sorghum and rye, and e) a second reference period without enzyme application. Different institutions conducted various analysis on the sampled medium, and KTG provided data on the performance of the bioreactors (T, gas yield etc.). Biopract monitored the production of various acids, evaluated the gas production and conducted an economic assessment. They revealed that the pectinase preparation stabilized the process when the temperature and acid concentration (in particular propionic acid) rised in the bioreactors due to the warm weather at that time point. The Technical University controlled the viscosity of the medium with novel equipment on side. Studies of the impact of the enzyme or substrate variation on the microbial community was carried out by the Helmholtz Zentrum München. Our institute monitored the pH, FOS/TAC and content of ammonium, dry matter, raw protein, raw ash, raw fat, raw fibre, starch, water-soluble carbohydrates, cellulose, hemicellulose and lignin, and calculated the biodegradability of raw fibre, starch, water-soluble carbohydrates, polymers of the lignocellulose and raw fat. Results showed that enzymatic pretreatment (100 g enzyme/t DM of substrate) of different substrate mixtures containing mainly maize silage increased the lignocellulose degradation, in particular hemicellulose and a substantial increase in specific energy production was obtained. In addition, the viscosity in the fermentation media was significantly reduced up to 18%. In conclusion, the addition of an enzyme preparation as biological treatment led to an economical operating improvement in efficiency of the biogas process. Based on that, the enzyme preparation was modified, tested in further industrial bioreactors by DSM and MT Energy and was patented. The preparation is marketed as Axiase for biogas processes and is sold all over Europe. 

 

In cooperation with KTG Agrar SE (Germany), DSM (Netherland), Biopract GmbH (Germany), Technical University of Berlin (Department of Biotechnology, Germany) and Helmholtz Zentrum München (German Research Center for Environmental Health, Germany).

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PRODUCT WEBPAGE: AXIASE

Deutsch: Entwicklung gesundheitsfördernder Futtermittel für Jungtiere durch Inklusion von Mykotoxinen (300 TEUR)

 

English: Development of health-promoting feedstuffs for young animals by inclusion of mycotoxins

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Summary: The aim was to decrease acute and chronic mycotoxicoses of calves and piglets by the formation of inclusion complexes, in particular the encapsulation of mycotoxins by cyclodextrins, focusing on the guest-host interaction. With the help of computer modeling, we simulated inclusion complexes of aflatoxin B1, ochratoxin A, zearalenone and deoxynivalenol and the cyclodextrins: α-, β-, γ- and  δ-cyclodextrin. The cyclodextrins α and δ exhibited undersized or oversized cavities for inclusion, respectively. For in vitro inclusion of mycotoxins, pure cyclodextrins (references) or an in-lab produced cyclodextrin mixture were applied, produced by enzymatic starch conversion resulting in a high content of β- and γ-cyclodextrin and mimicking nature. We established and validated the high performance thin layer chromatography for analyzing cyclodextrins. The stability of cyclodextrins and mycotoxins was tested in digestion simulations. These reflected the toxicity of mycotoxins by, inter alia, high stability in the gastrointestinal tract. Cyclodextrin α was more stable than β and γ, and the latter partially degraded in the gastric juice. We determined the complex formation in aqueous solution, and demonstrated an 100% inclusion of aflatoxin B1 by β-cylcodextrin. Spectroscopic (UV-VIS, Fluorescence) analysis revealed inclusions of aflatoxin B1, ochratoxin A and zearalenone by β -and γ-cyclodextrin and the in-lab product. The in-lab product, containing a mixture of cyclodextrins, was of advantage compared to pure, individual cyclodextrins, and showed good stability in lyophilized form at a storage of 6 months at -18 °C. The use of such product would reduce the costs by elimination of production steps such as purification of cyclodextrins. Deoxynivalenol was not sufficiently detectable in terms of an inclusion equilibrium with the applied methods and requires an investigation in an follow-up project.

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In cooperation with the German PROTEKUM - Umweltinstitut GmbH.

Deutsch: Grundlagen der Biogasgewinnung aus pflanzlicher Biomasse: Systemanalyse der mikrobiologischen Stoffumwandlung unter besonderer Berücksichtigung des Einflusses der Substratbereitstellung, der Intermediatbildung sowie der Prozessführung (2 MEUR)

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Teilvorhaben 1: Untersuchungen zum Einfluss der enzymatischen Vorbehandlung von Biogas Crops auf die Prozesskette der Methangewinnung (200 TEUR)

 

English: Fundamentals of biogas production from plant-based biomass: system analysis of microbiological material conversion under special consideration of the impact of substrate provision, intermediate formation and process control

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Sub-project 1: Determination of the impact of enzymatic pretreatment of biogas crops on the process chain of methane formation

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Summary: Polysaccharides of plant cell walls are of limited digestibility due to their cross-linking to lignin. To allow microbial conversion during anaerobic digestion, and by that increase the substrate utilization and process efficiency, substances or techniques for degradation are desired. On this basis, the objective was to investigate the effects of different commercial enzyme preparations in three digestion process stages. Selected energy plants of varying degrees of particle sizes (chopping lengths) were applied as digester feedstock. Enzyme preparations were chosen by enzyme assays, containing primary cellulase, pectinase, xylanase or laccase. The selected enzymes were added to the feedstock before the ensiling of plants, before the biogas process (pre-hydrolysis) or directly to fermenters as sole preparation or as mixtures. Pre-treated substrates were subsequently digested in biochemical methane potenial (BMP) tests. Beside the biogas and methane yield, the degradation degree of cellulose, hemicellulose and lignin, and the release of low molecular carbohydrates were investigated for evaluating the enzyme performance. A mass balance over the entire process was conducted for cellulose. Moreover, the mass and nutrient loss during ensiling, and the acid and alcohol spectra were analyzed. Additionally, the swelling of lignocellulose caused by addition of water in a pre-hydrolysis process was examined as a method of pre-treatment, with generally positive results. The aim of an improved substrate conversion of maize and rye and thus an enhanced biogas production by enzymatic pretreatments was achieved. Scientific fundamentals regarding the impact of enzymes on biogas processes were established. Enzymatic pretreatments in process steps before methanation showed potential for further developments.

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In cooperation with the German Brandenburg University of Cottbus-Senftenberg (BTU), Hamburg University of Applied Sciences (HAW Hamburg), Leibniz Institute of Agricultural Engineering and Bioeconomy (ATB), Bavarian State Research Institute for Agriculture (LfL), Technical University Munich (TUM), University of Hohenheim (UoH), Goethe Center for Scientific Computing (G-CSC) of the Goethe University Frankfurt/Main, Humboldt University Berlin and Johann Heinrich von Thünen Institute - Federal Research Institute for Rural Areas, Forestry and Fisheries.

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DOCTORAL THESIS