Title: Allergy Research at BCE
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
BCE will host the Alpha Winter Meeting on allergy research on Jan. 22nd, 2024 at Aarhus University, Denmark.
More than 40 participants will discuss 15 presentations from active researchers from academia and industry as well as younger researchers and students.
The meeting is focusing on active research in allergic diseases, ranging from molecular and cellular research to clinical and therapeutic applications. The mission of the meeting is to exchange and discuss scientific ideas and promote national and international collaboration in the field. The meeting has a particular focus on younger scientists.
We are looking forward to welcome all participants interested in the field.
For further information please click here.
Contact: Edzard Spillner, BCE
Lecture by: Master Student Kaya Helene Rosell
Title: Development and characterization of esophageal 3D co-culture system for studying epithelial-stromal interactions
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Epithelial tissues serve as protective barriers and maintain homeostasis of the gastroesophageal tissues that are vulnerable to diseases. The maintenance and function of these organs rely on epithelial-stromal interactions, highlighting the importance of paracrine signaling in tissue regeneration. While traditional 2D cultures fail to model these interactions effectively, 3D organoid cultures offer improved physiological relevance, though they still lack the complexity of in vivo environments. The project aims to develop and characterize 3D co-culture systems that integrate epithelial cells and fibroblasts to better mimic native tissue dynamics, enabling the study of epithelial-stromal crosstalk and tissue organization.
Master Student
Lecture by: Master Student Kristine Brix Poulsen
Title: Validation and characterization of CRISPR/Cas9 knockout of cytidine deaminase in human ectocervical epithelial stem cells.
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Recent research indicates that co-infection with Chlamydia trachomatis and HPV can drive oncogenesis in human ectocervical stem cells. A hallmark of cervical cancer is the presence of cytidine deamination-associated mutational signatures. To investigate the mechanisms linking co-infection and cytidine deaminase activity to cervical cancer, patient-derived human ectocervical epithelial stem cells expressing HPV16 E6E7 oncogenes were nucleofected with a CRISPR/Cas9 construct targeting specific cytidine deaminase. In this project, the generated knockout stem cells were validated and characterized using PCR, puromycin selection assays, fluorescent imaging and cytidine deaminase activity assay. These findings enable further investigations into the role of cytidine deaminase in cervical carcinogenesis.
Master Student
Lecture by: Master Student Sille Lykke Engermann
Title: Development of Biocompatible In Vitro Intestinal Scaffold by Volumetric Printing
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Gastrointestinal diseases affect millions worldwide and pose significant healthcare challenges due to their complexity and the lack of suitable research models. I will discuss some results from my master’s thesis, which explores tomographic volumetric printing to create simplified small intestine-like scaffolds using low-polymer-content GelMA hydrogel with enzymatic coatings, assessing the method's feasibility and material biocompatibility.
Master Student
Lecture by: Master Student Valentin Vacari Møller
Title: Humanization of allergen-specific nanobodies for passive immunization
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
This project focuses on the humanisation of three Api m 1-specific nanobodies developed by the group. The goal is to optimise their compatibility with the human immune system while maintaining their binding affinity, stability, and expression levels. Both nanobodies and nanobody-hIgG1 constructs are evaluated, expressed in bacteria or mammalian cells, and analysed using biolayer interferometry to determine binding kinetics. These efforts aim to further advance the development of diagnostic and therapeutic strategies against venom-induced allergic reactions.
Master Student
Lecture by: Master Student Alberto Ianis Trantea
Title: Synthetic Nanobody Yeast Display Platform for Selecting Allergen-Specific Nanobodies
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Synthetic nanobody libraries combined with yeast display technology, provide a versatile and efficient alternative to immune repertoire libraries, enabling the streamlined selection of allergen-specific nanobodies. In this talk, I will discuss the selection of Api m 1-specific nanobodies and their characterization alongside previously identified nanobodies developed in our lab, providing a foundation for developing targeted diagnostic and therapeutic tools for honeybee allergy treatments.
Master Student
Lecture by: Master Students Marc Marburger & Fie Larsen
Title: FEA and AI of 3D Liver Displacements During pneumoperitoneum and inertial focusing of nanoparticles in vessels of deformable tissue
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Two industrial master theses projects have been launched to improve surgical outcomes in laparoscopic liver surgery. Mathematical models of liver deformations and blood flow is developed and solved using the finite element method. Their geometry is based on segmented 3D image volumes and theoretical vessels.
Marc Marburger’s project:
Fie Larsen’s project:
Master Students
Lecture by: Assistant Professor Vineesh Indira Chandran
Title: A new approach to treating MASH
Place: Gustav Wieds Vej 10A, 8000 Aarhus C, Building 3140, Room 103.
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive disease of the liver that is currently affecting more than a third of the world’s adult population and is the leading cause of liver transplant, surpassing Hepatitis C-related complications. It is characterized by triglyceride accumulation, severe inflammation, and fibrosis. Due to the high global incidence and prevalence rates of MASH and their substantial economic burden on healthcare systems, early interventions are urgently needed. The exact molecular mechanisms underlying progression of MASH is an active topic of investigation, however a widely held hypothesis is that fat accumulation is the primary driver of the disease. Therefore, drugs targeting fat accumulation in hepatocytes resulting in hepatic steatosis is a topic of active investigation. In this study, we developed a novel antibody-drug conjugate (ADC) targeting asialoglycoprotein receptor 1 (ASGPR1) on liver hepatocytes and characterized the stability, specificity, localization, and biodistribution in liver hepatocytes using in vitro and in vivo models; with potential implications in the treatment of MASH.
Lecture by: Postdoc Tong Tong
Title: The Human Cortex Lab: A Pioneering Human Brain Tissue Platform and Insights into Glioblastoma Cell Excitability
Place: Gustav Wieds Vej 10A, 8000 Aarhus C, Building 3140, Room 103.
Translating basic cancer neuroscience research into clinical applications is challenging, primarily due to the difficulty of bridging the gap between research findings and effective patient treatments. Many therapeutic agents fail in clinical trials, often because preclinical models inadequately replicate human biology. Limited access to patient-derived samples, preservation difficulties, and the lack of integration between biological and clinical data further hinder progress. The Human Cortex Lab addresses these challenges by providing an advanced human brain tissue platform that offers fresh tissue collection, organotypic slice cultures, and viral transduction techniques. This platform links clinical and biological data for comprehensive analyses in collaboration with brain tumor and neuroscience researchers. One research project, using this platform, investigates the excitability of glioblastoma (GBM) cells. Fluorescence-guided whole-cell patch-clamp recordings in human brain slices revealed that 56% of GBM cells at the tumor’s leading edge exhibit neuron-like excitability, generating aberrant action potentials. These findings shed new light on GBM cell behavior and underscore the platform’s critical role in advancing translational research and developing targeted therapies.
Lecture by: Postdoc Pon Ganish Prakash
Title: Comparing the physiological and transcriptional fidelity of 3D organoid models and Native tissue
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Organoids are 3D tissues grown from organ specific adult stem cells, that mimics the functional, structural and biological complexity of human organs. These miniature models can self-organize and differentiate, offering a close approximation to in vivo tissues. Their potential as near-physiological models have led to a surge in research, highlighting their vast applications, particularly in disease modelling and drug discovery. However, their ability to accurately capture transcriptional signatures due to the lack of the in vivo microenvironment, i.e due to the absence of key cell types like stromal and immune cells, remains debated. This presentation will discuss our ongoing research, using single cell sequencing and bioinformatics to evaluate how well patient-derived cervical organoids replicate the cellular diversity and gene expression patterns of actual cervical tissue biopsies.
Lecture by: Guest Researcher Abid Hussain
Title: Identification of a Novel Allergenic Protein from Paper Mulberry Pollen
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Broussonetia papyrifera (Paper Mulberry) is a widely distributed tree and it has a significant impact on public health due to its allergenic potential. In Pakistan, it is a major sensitizer for patients with allergic rhinitis and asthma. Our group recently identified a 12-15 kDa non-specific lipid transfer protein (nsLTP) from Paper Mulberry pollen, now recognized as Bro p 3.0101, which has been accepted by the IUIS/WHO Allergen Nomenclature Sub-Committee. In this seminar, I will discuss the identification and characterization of this newly recognized allergen, its unique immunological reactivity profile, and its implications for advancing allergy diagnostics and targeted therapies.
Guest Researcher
Lecture by: Postdoc Éloïse Marie Mussard
Title: Development and characterization of a piglet intestinal organoid model to study the effects of postbiotics on the intestinal epithelium
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
In piglets, diarrhea is commonly observed after weaning and is associated with a dysfunction of the intestinal epithelial barrier. In the context of the reduction of antibiotics use in farms, new strategies are implemented to preserve the digestive health of piglets at weaning. The use of postbiotics (nutritional products derived from microorganisms) seems to be a promising strategy but their effects on the piglet intestinal epithelium are not well known. The objective of my PhD was to develop and characterize a model of piglet intestinal organoids allowing to test the effects of postbiotics targeting the barrier function of the intestinal epithelium. By culturing piglet intestinal epithelial stem cells in an extracellular matrix protein gel, three-dimensional (3D) structures were formed by a monolayer of polarized epithelial cells and including several cell types. Based on gene expression analyses, we showed that piglet intestinal organoids partially retained the phenotype related to their original digestive segment while they did not maintain the specific gene expression profile of suckling or weaned piglets. Our characterization of 3D organoids confirmed that the apical side of epithelial cells is oriented towards the lumen and is therefore not easily accessible to study the effects of nutritional products. We then developed an organoid cell monolayer culture model that allows access to the apical side of the cells and to study the barrier function of the epithelium. Using this model, the effects of products derived from microorganisms: butyrate, a metabolite produced by the intestinal microbiota, and two postbiotics. We also studied these microorganism-derived products in the context of epithelial barrier dysfunction induced by the mycotoxin deoxynivalenol (DON). Taken together, our results indicate that the piglet intestinal organoid model is useful for studying the physiology of the intestinal epithelium in a gut segment-specific manner. Cell monolayers derived from piglet intestinal organoids allow access to the apical side of the cells and can be used to demonstrate the effects of microorganism-derived products on the epithelial barrier. These new tools can be used in many contexts to study in vitro the porcine digestive epithelium for veterinary and biomedical research.
Lecture by: Master Student Matous Najman
Title: Computational Study Of The Immune System Response To Bee Venom
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Development of immune therapy can be aided by computational modelling, helping us to understand mechanisms of sensitivity and allergic reaction, and create predictions for immune system development with and without the therapy. The main hypothesis suggests that a computational model can be developed to model the immune system reaction to bee venom. Moreover, it is hypothesized that such model can be validated and altered using clinical and/or experimental data. He will present findings from his thesis works.
Master Student
Lecture by: Postdoc Anne-Kathrine Kure Larsen
Title: Inka-PAK4 protein crystals as tool to study intracellular mechanobiology
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Cells and tissues are affected by and can respond to physical and biochemical changes of their extracellular environment. Several methods exist to mimic the extracellular environment to study these responses, as well as tools to measure cellular forces from the outside. However, mechanostimulation from the intracellular environment is currently challenging. This presentation will focus on the characterization of a novel tool, inka-PAK4 protein crystals, to physically stretch a cell from the inside, while it also has the potential to assist the measurement of intracellular forces.
Lecture by: Postdoc Naveen Kumar Nirchal
Title: Dietary Modulation of Gastroesophageal Tissue Regeneration Through Organoids and Single-Cell Sequencing
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Gastroesophageal tissues, including the esophagus, gastroesophageal junction, and stomach, are vital for digestive health. Several risk factors, such as male gender, age, smoking, GERD, high-fat diet-related obesity, and Vitamin A deficiency, can disrupt their function and increase the risk of Barrett's esophagus (BE), a condition that elevates the risk of esophageal adenocarcinoma. This presentation will focus on the role of retinoic acid (RA), an active metabolite of Vitamin A, in regulating gastroesophageal tissue homeostasis.
Lecture by: PhD Student Bjarke Krogstrup Jensen
Title: Bi-specific Nanobody-based IgG for Blocking the Major Honeybee Venom Allergen Api m 1
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Hymenoptera venom is the most common cause of anaphylaxis. This occurs due to an allergic reaction, triggered by allergens binding to IgE/receptor complexes located on the surface of effector cells. In this talk, I will characterize different allergen-specific nanobody constructs and show blocking of the binding between the allergen and the IgE/receptor complexes, inhibiting the allergic reaction. These findings provide promising evidence for utilizing nanobody constructs as a passive immunotherapy approach for protection against anaphylaxis in honeybee venom allergy.
Lecture by: PhD Student Catalina Suarez Londoño
Title: Open Foam Characterization for Computer Simulation of Mechanical Cues in Cell Differentiation
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
The stiffness of the extracellular matrix (ECM) plays a significant role in cell differentiation, although the underlying mechanisms remain unclear. Biomaterials composed of different ratios of polycaprolactone (PCL), dioxane, and water, forming open foam structures with macro- and nanopores, are used to investigate these effects. Digital twins of these foams are generated through 3D reconstructions from X-ray tomography and electron microscopy images, enabling the analysis of properties such as porosity, tortuosity and local thickness. Correlating material composition with physical characteristics allows for in silico studies of how mechanical cues influence cell differentiation and motility.
Lecture by: Postdoc Bjarke Nørrehvedde Jensen
Title: Anisotropic Biomaterials with Wireless Electromagnetic Stimulation for Guiding Neural Regeneration
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Nerve injuries affect millions of people worldwide and the current surgical procedures have limited success in repairing damaged tissue. In this presentation I will cover the development of a wireless electromagnetic stimulation system that we have combined with filamentous gelatin-based hydrogels for providing electrical, chemical, and mechanical cues to enhance regeneration after peripheral nerve injuries.
Lecture by: Master Student Lone Hallum
Title: Characterization of Polymeric Scaffold Properties
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Polymeric scaffolds used for tissue regeneration, can be fabricated through thermally induced phase separation. By varying the underlying chemical composition, the resulting scaffolds differ both in morphology and mechanical properties. Through mechanical testing and computational modelling, some of the changes can be quantified and analyzed. In this presentation, I will discuss the utilized methods and some of my findings from the project.
Master Student
Lecture by: Associate Professor Thomas Lykke-Møller Sørensen
Title: X-Ray tomography for imaging organoids
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
X-ray tomography is a tool for the 3D analysis of samples in life sciences. We have used the P-14 beamline at EMBL/DESY in Hamburg to image organoids and develop labelling techniques. I’ll give a short update on progress and challenges and present some recent results.
Lecture by: Master Student Jesper Rosendahl Laursen
Title: ”Cell membrane lipid profiling of bacterial cultures during growth and impact on shelf-life/stability”
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
This project delves into the study of the lipid bilayer of Lactic Acid Bacteria, a fundamental component of the dairy and probiotics industry. It focuses on understanding how various environmental stressors influence the evolution of the lipid bilayer and the stability of Lactic Acid Bacteria growth. The project aims to unravel the relationship between growth conditions and membrane composition, thereby contributing to our knowledge of Lactic Acid Bacteria cultures.
Master Student
Lecture by: Master Student Fie Karlskov Larsen
Title: ”R&D to Thesis: Modelling Liver Deformations in Laparoscopic Liver Surgery”
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
In collaboration with BK Medical, a GE healthcare company, who specializes in advanced surgical imaging solutions, particularly high-resolution ultrasound systems for real-time imaging, a project has been launched. The aim is to improve surgical outcomes in laparoscopic liver surgery by developing mathematical models of liver deformations to create finite element models based on segmented 3D image volumes. The models will be used to quantify and validate deformations against real data and literature values.
My R&D study focuses on becoming familiar with programs such as 3D Slicer, COMSOL and python, while gaining a better understanding of anatomy, clinical relevance, liver cancer and elasticity theory through a literature study.
Master Student
Lecture by: Postdoc Anne-Sofie Ravn Ballegaard
Title: Is IgE a suitable target in allergy therapy?
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
The antibody isotype IgE is the main player in type I hypersensitivity. Hence, targeting IgE is a major option for therapeutic intervention in allergic diseases. Available treatment forms rely merely on inhibition of the IgE binding to its receptor on effector cells. However, molecular approaches to displace IgE from its receptor on effector cells without risk of activation have been described.
In this presentation, I will give an update on the development of candidate molecules that have the capability of inhibition as well as displacement activity.
Lecture by: PhD Student Pon Ganish Prakash
Title: "Single-cell RNA transcriptomics of cervical exfoliated cells during carcinogenesis reveals potential biomarkers”
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Cervical cancer is a prevalent gynecological malignancy despite the efficacy of various screening methods. Persistent human papillomavirus (HPV) infection is the primary cause of Cervical cancer. Understanding the multicellular ecosystem and signaling events at different stages in cervical carcinogenesis enables the identification of early detection biomarkers, which is critical for impeding the transition from low-grade cervical intraepithelial lesions to cancer. Here, I will discuss the recent study revealing potential biomarkers and cellular pathogenesis in cervical carcinogenesis using Single-cell RNA sequencing of cervical exfoliated cells.
PhD Student
Lecture by: Master Student Pernille Broch
Title: ”Establishment of selecting artificial immune repertoires via yeast surface display”
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
The presentation will focus on the generation of nanobodies with specificity for given target structures from synthetic yeast display libraries. This technology could enable circumvention of time constraints and need of immunization and might have the potential to provide antibodies against immunologically silent epitopes. Benefits and pitfalls of the approach and results obtained in the project so far will be presented.
Master Student
Lecture by: Professor Peter Lindberg Nejsum
Title: Parasite extracellular vesicles show diverse functions in their host
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Helminths are parasitic worms that often cause chronic infection by releasing excretory/secretory products that modulate the host’s immune response. We, and others, have shown that extracellular vesicles (EVs) are released with the excretory/secretory products. To understand the potential role of EVs in host-parasite interaction, we have profiled their content and identified microRNAs and proteins that may be essential for parasite survival. To further understand their role, we have conducted several functional studies, and strikingly, we find that EVs may play a diverse role in host-pathogen interaction depending on parasite species. While we find that Ascaris release EVs that suppress the host immune response and are selectively internalized by monocytes, Trichuris-derived EVs did not modulate the immune response but selectively packed microRNAs in EVs that can suppress cancer genes. Other parasites release highly immunogenic EVs, suggesting a central role in pathogenicity. In conclusion, though we find that EVs are critical in host-parasite interaction their role is context and species-dependent.
Lecture by: Postdoc Kristian Juul-Madsen
Title: Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer’s Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer’s Disease-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis.
Lecture by: Josephine Baunvig Aagaard (Postdoc in the Immunological Biotechnology group)
Title: Nanobodies for Prevention of Anaphylaxis in Honeybee Venom Allergy
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Insect venom allergy is the most common cause of anaphylaxis. Central in the allergic reaction is the binding of venom allergens to IgE/receptor complexes on the surface of effector cells triggering immediate allergic reactions and potentially anaphylaxis. In this presentation, I will demonstrate how allergen-specific nanobody formats can block the binding of allergens and thereby prevent the subsequent allergic reaction. These findings provide the functional and structural basis for establishing a passive immunotherapy approach for protection against anaphylaxis in honeybee venom allergy.
Lecture by: Mette Steen Toftdal (Industrial Ph.D. student from the group of Nanofiber Technology and Cellular Engineering)
Title: Fighting Diabetes – Combining Beta Cell Therapy with Tissue Engineering
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Diabetes affects over 400 million people worldwide, and while cell therapy holds promise for curing Type 1 diabetes, low retention rates and inadequate cell survival remain ongoing challenges. Combining cell therapy with tissue engineering may provide a solution to these challenges. In this presentation, I will introduce a developed device for beta cell transplantation. The device, consisting of PLCL/GelMA/alginate coaxial nanofibers embedded in an alginate hydrogel, was characterized physically and mechanically, as well as analyzed for its interaction with beta cell clusters. The device shows potential for improving beta cell therapy and overcoming challenges in cell survival.
Lecture by: Postdoc Naveen Kumar Nircha
Title: "From Organoids to Organism: Unraveling the Gastroesophageal Junction Evolution Through Single-Cell and Spatial Transcriptomics”
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
The gastroesophageal junction (GEJ) is a key anatomical site prone to stress-induced metaplasia and subsequent esophageal adenocarcinoma (EAC), a cancer with a notably low five-year survival rate. In our study, we utilized single-cell transcriptomics and spatial analysis to identify the cellular and molecular intricacies of the GEJ in healthy mouse tissue, spanning from embryonic to adult stages. We uncovered distinct transcriptional profiles and signaling pathways in epithelial and mesenchymal cells that are pivotal in GEJ development. Through advanced techniques like organoid models, lineage tracing, and single-molecule RNA in situ hybridization, we have further deciphered the regulatory mechanisms of squamo-columnar junctional epithelial cells in the GEJ. Our research illuminates the molecular framework of GEJ development and provides comprehensive insights into the interactions between fibroblasts and epithelial cells, enhancing our understanding of tissue heterogeneity, homeostasis, and regeneration.
Speaker: Associate Professor David Bernick from University of California Santa Cruz
Title:
"Engineering the future with Synthetic Bio"
Place: Auditorium 1170-347, Ole Worms Allé 3 , 8000 Aarhus C
David Bernick is an Associate Teaching Professor of Biomolecular Engineering at the University of California Santa Cruz campus, USA. Across both his teaching and research, he explores topics in synthetic biology and bioinformatics, emphasizing opportunities to aid under-resourced communities and the technical challenges in support of those communities. Over the past decade, he has had the pleasure of mentoring undergraduate students in the IGEM program (International Genetically Engineered Machines). Together, they have taken on projects in biofuel development, diabetes management, food insecurity, biotoxicity of water, agricultural plastic waste and access to contraceptives. Each of these areas share the larger goal of supporting our planet while normalizing sustained access to a flourishing life experience.
Dr. Bernick will discuss recently published (view paper) work to produce Exendin-4 with a consumable microbial chassis to improve access to this GLP-1 agonist. This peptide hormone and its derivatives are useful tools in the management of some forms of diabetes caused by insulin regulatory deficiency (link to paper). He will also discuss the IGEM program as a focus for undergraduate education for those interested in bioengineering, bioinformatics and other translational professions.
David Bernick
Associate Teaching Professor
Biomolecular Engineering
University of California
Santa Cruz, Ca
dbernick@ucsc.edu
Speakers: Bekir Engin Eser & Frederik Vig Benfeldt
Titles:
"Expanding the Toolbox of Fatty Acid Hydratases: A Thermostable Hydratase from Marinitoga piezophila with a Low Temperature Optimum and Unique Regioselectivity"
"Multi-enzyme/whole cell catalytic production of short-medium chain diols and diacids"
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
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1st Speaker : Bekir Engin Eser
Title: Expanding the Toolbox of Fatty Acid Hydratases: A Thermostable Hydratase from Marinitoga piezophila with a Low Temperature Optimum and a Unique Regioselectivity
Abstract: Fatty Acid Hydratases (FAHs) catalyze the addition of water to unsaturated fatty acids to generate hydroxy fatty acids (HFAs) as products. Since HFAs have diverse application areas from materials and cosmetics industries and possess beneficial bioactivities, their benign enzymatic synthesis from abundant oils has attracted a lot of attention in the recent decade. One common challenge with biocatalytic conversions, including FAHs, is the stability of enzymes towards process conditions. Thus, we looked at Nature to find thermostable FAHs and characterized FAH ortholog from the thermostable and piezophilic organism Marinitoga piezophile. As expected, MpFAHY showed high thermostability, retaining over 90 % of its activity even after 30-min incubation at 70 °C. However, interestingly, the enzyme showed the highest activity at a much lower assay temperature of 20 °C, with sharp decreases above and below this temperature. This might indicate a physiological function of the enzyme, e.g. being part of a cold adaptation mechanism of the organism, which normally lives at 45-70 °C. Moreover, the purified enzyme requires NaCl to be active, consistent with the living habitat of its source organism. Another interesting property of the enzyme was its unique regioselectivity. MpFAHY was able to produce a mixture of 10-OH and 13-OH products from linoleic acid, with 13-OH being the preferred product, which is not a common property of wild-type FAHs.
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2nd Speaker: Frederik Vig Benfeldt
Title: Multi-enzyme/whole cell catalytic production of short-medium chain diols and diacids
Abstract: The rising issue of plastic pollution and the limited motivation for mechanical recycling urges the academia and industry to develop the technologies that enable close- or open- loop recycling and upcycling. To address this, the ACTPAC project seeks to develop a practical method to transform chemically inert C-C backboned plastic waste, specifically polyethylene (PE), into high-value monomers and biochemicals.One of the pivotal challenges in this transformation is the biotransformation of alkanes into α,ω-alkandiols and diacids, particularly due to the difficulty in directing C-H oxy-functionalization at the least reactive terminal positions. The ACTPAC project aims to utilize the unique capabilities of Cytochrome P450 (CYP450) enzymes to overcome this challenge. Our strategy involves screening and characterization of promising CYP153A orthologs capable of hydroxylating and oxidizing medium length alkanes into α, ω-diols and diacids. Engineering of selected CYP153A enzymes to fine-tune their specificity and activity towards targeted substrates through computational methods and machine learning algorithms. Lastly, scale-up is aimed to be conducted in large-scale bioreactors, with a focus on enhancing efficiency, cofactor regeneration, and fine-tuning reaction conditions to maximize yields.
Speakers: Laura Munoz, Susmit Chakraborty & Timothé Philippon
Title: Relevance of H2 consumption characteristics for acetogenic and methanogenic bioelectrochemical CO2 reduction
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Acetogens and methanogens reduce carbon dioxide with H2 as electron donor to obtain energy. This autotrophic metabolism is of interest for CO2 valorization biotechnologies, such as gas fermentation and even more microbial electrosynthesis. Indeed, the ability of those microbes to rapidly consume H2 could enhance electrochemical H2 production, once put near an electrode performing proton reduction. This hypothesis could be important for bio-electrochemical applications if proven to be true. To test our hypothesis, we must first characterize differences in H2 consumption characteristics between available acetogenic and methanogenic strains. Understanding those differences will also aid optimal strain selection for microbial electrosynthesis.
First, we determined the H2 threshold, i.e. the H2 partial pressure at which acetogenesis or methanogenesis halts, for diverse acetogenic (1) and methanogenic strains and observed strong differences. The observed H2 thresholds suggest significant variations in bioenergetics, potentially influencing growth yields and kinetics as well.
Furthermore, we determined the H2 consumption kinetics of different acetogens over a wide range of H2 initial concentrations. Interestingly, we observed that their H2 consumption followed first-order kinetics at under-saturated H2 levels. Our results thus suggest that acetogenic conversion rates can be increased by increasing the H2 partial pressures. In addition, we found strong differences in the first-order H2 consumption coefficient. We hypothesize the kinetic differences can be in part related to different types of hydrogenases of the strains.
In addition, to predict the performance of these strains in bioelectrochemical reactors, we incorporated the H2 threshold and kinetic data into mathematical models. These models simulate the behaviour of the strains under various conditions, such as electric current input, providing useful insights to optimize H2 utilization rates and enhance process efficiency.
Overall, our comprehensive new understanding of H2 dynamics for these hydrogenotrophic strains will guide the selection of suitable biocatalysts for microbial electrosynthesis.
References
1 Munoz, L; Philips, J. No acetogen is equal: Strongly different H2 thresholds reflect diverse bioenergetics in acetogenic bacteria. Environ Microbiol 2023;25:2032–40.
Lecture by: Professor Dr.-Ing. habil. Selin Kara, Department of Biological and Chemical Engineering, Aarhus University, Denmark
Title: "Process intensification for enzymatic decarboxylations: Transitioning from lab to industrial scales”
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303
The application of nature’s catalysts, “enzymes,” for the synthesis of chemicals is a crucial emerging field of industrial biotechnology to meet the current and future needs of our society for sustainable manufacturing of chemicals. Nature uses an elegant and efficient synthetic strategy: Coupling enzymes in multi-step pathways without intermediate isolation and purification steps with precise spatial control of catalysis. Inspired by nature, the design of multi-step biotransformations has been attracting significant attention within the biocatalysis community. The talk will introduce enzymatic decarboxylation reactions (in cascading systems), exploring the use of non-conventional media, enzyme immobilization, and different operational modes for enhancing the volumetric productivity of these biocatalytic applications.
Lecture by: Maria Florencia Bambace & Herald Wilson Ambrose
Title: "Reuterin-based biological treatment to mitigate methane emissions from pig slurry storage”
Place: Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303.
Methane (CH4) accounts for more than 90% of farmgate greenhouse gas (GHG) emissions in pig farming, with 80% being produced during manure management. In intensive pig production, slurry is stored in manure pits under the barn floor for short term storage (1 to 6 weeks) and in outside storage tanks for longer storage periods. During this time, CH4 is emitted as a result of microbial degradation of organic substrates present in the pig feces, combined with the anaerobic conditions developed under the slurry surface, which promote the activity of methanogens. Acidification is considered a benchmark technology for mitigating CH4 emissions from stored slurry. However, there are several associated drawbacks such as safety issues in application, soil sensitivity to increased sulphur loads during land application, and inhibitory effects on biogas production. Other chemical additives raise further environmental concerns; hence the need for a biological alternative is highly sought for CH4 mitigation in slurry storage.
Biological treatments studied thus far, utilizing microbial or enzymatic additives have shown little to insignificant potential for CH4 mitigation in pig and cattle slurry storages. In this seminar talk, we will present and discuss the results of a successful biological treatment aimed at inhibiting methanogenic activity in slurry storages, conducted on a laboratory scale headspace emission setup. The biological additive involves the use of Limosilactobacillus reuteri, which in the presence of glycerol produces reuterin, a broad-spectrum antimicrobial agent. We assessed the impact of endogenously produced reuterin on CH4 emissions from pig slurry by initially introducing both L. reuteri and glycerol into the slurry, which was then stored for a period of 26 to 30 days, during which CH4 emissions were measured. We also optimized the dosage combination of L. reuteri and glycerol. Our results showed that endogenously produced reuterin reduced CH4 emissions by 74-90% compared to untreated slurry. The environmental and biological aspect of our study will be further discussed, highlighting this novel approach as a promising alternative to H2SO4 or chemical surfactant treatments for reducing methanogenic activity in pig slurry storages.
Lecture by: Nele Van Dessel, CEO from Ernest Pharmaceuticals (USA)
Title: "The use of Salmonella bacteria to treat cancer”
Place: Zoom, https://aarhusuniversity.zoom.us/j/62375855091
The microbial biotechnology course will host an online guest lecture on the use of Salmonella bacteria to treat cancer.
The guest speaker is Nele Van Dessel, CEO from Ernest Pharmaceuticals (USA), a small startup company, trying to bring this new and intriguing microbial biotechnology to the market.
