Die Master Thesis ist der wissenschaftliche Kern Ihres Studiums: Ihre Fachkurse wählen Sie bereits im Hinblick auf das Thema Ihrer Thesis, welches Sie vor Studienbeginn bestimmen. Basierend auf den theoretischen Grundlagen des Studiums beantworten Sie eine konkrete Fragestellung in Ihrem Forschungsgebiet. Sie erarbeiten Lösungen mit Relevanz für Forschung, Wirtschaft und Gesellschaft, meist in Zusammenarbeit mit nationalen oder internationalen Partnern. Entsprechend arbeiten Sie in einer Forschungsgruppe am Institut für Biotechnologie in Wädenswil oder extern bei einem Industrie- oder Forschungspartner. Mit der Thesis demonstrieren Sie nicht nur Ihr Wissen und Ihre Kompetenz, sondern auch die Fähigkeit, sich erfolgreich in einer Forschungsgruppe zu integrieren und Ihre spezifischen Kenntnisse in Ihrem Wissenschaftsgebiet zu erweitern.

Für die Master Thesis konzentrieren Sie sich auf einen bestimmten Bereich der pharmazeutischen Biotechnologie im Rahmen einer Forschungsgruppe. Dabei planen und arbeiten Sie weitgehend selbständig in Absprache mit Ihrer Betreuungsperson und allfälligen externen Forschungs- oder Industriepartnern. So vertiefen Sie nicht nur Ihre wissenschaftlichen und technischen Kompetenzen, sondern eignen sich auch Kenntnisse in Projektmanagement an. Ein Forschungsprojekt langfristig und erfolgreich zu verfolgen, erfordert und schult Ihre Flexibilität, beispielsweise, wenn wissenschaftliche Hypothesen überdacht oder Versuchsanordnungen angepasst werden müssen. Für die Thesis ist ein Zeitraum von acht Monaten vorgesehen, den Sie individuell während Ihrer Gesamtstudienzeit einplanen können.

Das Thema Ihrer Master Thesis wählen Sie in einer der folgenden Forschungsgruppen:

• Diagnostic of plant pathogenic viruses (together with Bioreba)
• Antiviral testing of textiles (together with Chahan Yeretzian)
• Genome sequencing, assembly and annotation (together with the group of Theo Smits from IUNR)
• Secondary metabolites of Streptomyces and activation of silent biosynthetic gene clusters
• Production of recombinant proteins and inhibitor screening (together with the group of Rainer Riedl)
• Modification of yeasts for production of biological derived products from waste (together with Circular Industries)

Contact: Prof. Dr. Martin Sievers

• Integrated Bioprocess Development
  Modern bioprocesses for pharmaceuticals, recombinant proteins, food ingredients or cosmetics need to be designed with a holistic view on the entire production chain. A sound understanding of culture behavior, cell biology and genetics has to be combined with bioreactor technology, tailored analysis, monitoring and control strategies. Automated workflows and ‘smart’ data exploitation concepts (e.g. soft sensors, model-based predictions & control, digital twins) have become essential tools in R&D and industrial biomanufacturing.
  Thesis topics on integrated bioprocess development, for different organisms, products and applications, are routinely available in our research group. Each project harbors its own challenges, and many are conducted in direct collaboration with industry partners, innovative startups or international academic institutions. We invite you to get in touch with the group leader for more information on current projects (details confidential).
• Cell-based Pharmaceutical Products
  Many established and innovative pharmaceutical products, with tailored, multifunctional properties, contain cells or cell parts as the pharmacologically active entity. Examples include live vaccines, prodrug systems, tumor-targeting bacteria, whole-cell drug carriers, or bacteriophages. For clinical application, it is essential that these cells can be produced under strictly controlled conditions, and ideally in a way that enhances their quality-relevant properties. Often, dedicated bioassays (e.g. cell culture models for binding and uptake, kinetic profiling or pharmacological activity) need to be available right next to the bioreactor to obtain the necessary information for efficient optimization.
  Circulating between biological testing and technical optimization, we support different companies and research partners in their efforts of developing optimal products. Please get in touch for more information on the currently available topics.
• From Analytics to Diagnostics – A Detailed Look on Cells
  In the context of bioprocessing, the cell is the central “biofactory”, expressing the compounds of interest. Viability status, replicative age, metabolic activity, productivity, and many other cell-biological parameters are of high importance to the process engineer and should ideally be easy to observe. Unfortunately, this is not always the case, and only possible by use of elaborate sensors or analysis technologies, combined with specially developed staining assays, reporter strategies, and/or data mining tools (e.g. machine learning, multivariate data analysis).
  The same analysis technologies can be applied to develop and optimize diagnostic concepts, e.g. in the early detection of parasitic diseases, drinking water contaminations or phytopathology. We routinely develop and apply dedicated cell-focused analysis tools and technologies for use in bioprocess monitoring and different diagnostic settings. Different master thesis projects are available for students interested in creative development work and applied data science.

Contact: Dr. Lukas Neutsch

• Expression, purification and bioanalytics of therapeutic monoclonal antibodies and fragments thereof
• Investigation of role of glycosylation in antigen-antibody binding interaction
• Expression, purification and bioanalytics of various human cathepsin candidates (includes mammalian expression systems)
• Episomal expression, purification and bioanalytics of human Fc Gamma Receptors and neonatal Receptor FcRn (includes mammalian expression systems)
• structure-activity relationship and analysis of enzymatic mechanism in bacteriophage tailspike proteins (includes cloning, expression in bacterial expression system, protein purification and diverse set of bioanalytical methods with assay development
• Bacteriophage Engineering

Contact: Prof. Dr. Sabina Gerber

• Surface functionalization of extracellular vesicles (EVs) for target-specific delivery of therapeutic proteins
• Investigation of the role of cysteine cathepsins in hypoxia mediated cancer cell invasion and metastasis using cell-based imaging assays
• Establishing of novel pharmaceutical formulations for bacteriophages / phage proteins
• Characterization of primary fibroblasts from patients with implant-associated fibrosis to identify novel therapeutic targets

Contact: Prof. Dr. Steffi Lehmann

• Development of plant based biopolymers for the use of pharmaceutical drug delivery systems. 

Contact: Dr. Andrea Baier

• Isolation, characterization, and genome sequence analysis of novel bacteriophages for the specific control of pathogenic bacteria
• Characterization of phagobiomes
• Conservation of bacteriophages by freeze- and spray drying
• Combinatorial effects of bacteriocins and bacteriophages in the control of pathogenic bacteria
• Heterologous cloning, expression, and characterization of phage-encoded endolysins
• Heterologous cloning, expression, and characterization of phage-encoded tail spike proteins
• Construction of recombinant temperate bacteriophages to reprogram the bacterial host
• Phage breeding – expanding phage host ranges by guided evolution
• Optimization of bacteriophage propagation in liquid culture at lab scale 

Contact: Prof. Dr. Lars Fieseler

• Development of isothermal DNA amplification methods for pathogen detection: This involves the purification of DNA polymerases and helicases (expressed in E. coli) and assay optimisation.
• Identification of novel target sites for covalent small-molecule antagonists: Purification of proteins (expressed in human cells, insect cells or CHO cells) and characterisation of putative target residues through structure-function studies and mass spectrometry.
• Development of small-molecule antagonists for disease-relevant proteins: Screening of libraries, optimisation of compounds, and functional characterisation through biochemical and cellular assays.

Contact: Dr. Kerstin Gari

• Topic 1: Comparative genomics to determine the phytopathological potential of Erwinia oleae DAPP PG-531
  Erwinia oleae DAPP PG-531 (LMG 25322^T) was isolated as olive knot endophyte but can in collaboration with Pseudomonas savastanoi pv. savastanoi cause disease of olive trees, called olive knot disease. The genome of this strain has been sequenced, autoassembled and published as a draft genome. An improvement of the genome assembly still is required to work well with it for comparative genomics and to draw some important conclusions. For this, the genome will have to be sequenced using a long-read technology. Additional, using comparative genomics with genomes from other Erwinia spp., the potential to be a pathogen will be examined in detail.
• Topic 2: Comparative genomics of Phytobacter spp. and related species
  Novel clinical isolates are appointed as members of the Enterobacteriaceae, all belonging to the genus Phytobacter. Some of the current isolates are highly resistant to different antibiotics. Different genomes of Phytobacter spp. were determined in the last years. Some of these still require a more detailed assembly, while others are fine for comparison. Comparative genomics of the different members of this genus will be done to determine differences between the different species within this interesting genus.
• Topic 3: Assembly and analysis of the genomes of two clinical Pantoea agglomerans isolates.
  We recently obtained and sequenced two Pantoea agglomerans strains that were isolated from a thorn wound. To be able to compare and visualize differences to the already available collection of P. agglomerans strains, the genomes will have to be assembled and annotated. Based on comparative genomics, we will draw first conclusions on the potential of the two strains in the field of pathogenicity, antibiotic resistances, biocontrol, or metabolism.
• Topic 4: Degradation of 17b-estradiol-3-sulfate (E2-3S) by Pseudomonas spp.: a genomics approach
  In a recent master work, we isolated many different bacterial species able to degrade E2-3S, a potential endocrine disruptor that appears to be present in the environment. Some of the isolates were members of the Pseudomonas putida group, closely related to Pseudomonas japonica based on 16S rRNA gene sequencing. In this study, we will do complete genome sequencing of one of these isolates and characterization of the biodegradation potential, both in silico and in vitro. Additionally, we will perform comparative genomics with other members of this group and determine whether Pseudomonas wadenswilerensis and further members are able to grow with E2-3S, also both in silico and in vitro.

Contact: Prof. Dr. Theo H.M. Smits

• Development of cell therapeutics based on human mesenchymal and induced pluripotent stem cells (focus on mass propagation and differentiation in bioreactors, work with spheroids and microcarriers)
• Intensified and continuous upstream processing in modern monoclonal antibody productions (N-1 perfusion, high-seed fed-batch production, continuous mAb production)
• Novel low-cost culture media for plant cell culture-based products of cellular agriculture
• Development of food additives and food based on plant cell cultures (co-operation with our foodstuff technologists)

Contact: Prof. Dr. Regine Eibl

• Scale-down and scale-up of biopharmaceutical production processes based on microorganisms, plant cells, animal cells and human cells (Co-operation with the team of Regine Eibl and companies, the topic may include medium development)
• Bioreactor characterization, design and tests for biopharmaceutical applications (Usage of classical bioengineering tools and modern methods such as Computational Fluid Dynamics, Particle Image Velocimetry, etc.)
• Bioreactor development for the production of in vitro meat (including cell cultivations and the production of myofibers)
• Novel cellular agricultural approaches for microorganism-based products suitable for human nutrition (e.g. single cell protein, mushrooms)

Contact: Prof. Dr. Dieter Eibl

• Biotechnological production of enzymes in fermentation scale and optimization of fermentation conditions with regard to enzyme activity and product formation.
• Combination of enzymes from different microorganisms to integrate novel metabolic pathways into E. coli or yeast.
• Establishment of new enzyme cascades for the production of fine chemicals.

Contact: Dr. Christin Peters

• Production of renewable cosmetic, fragrance or flavour ingredients (80% experimental /  20% theoretical work)
• Use of plant-derived lignin polymers in renewable plastics or plasticisers (80% experimental /  20% theoretical work)
• Pretreatment of lignocellulosic biomass for renewable chemicals production (80% experimental /  20% theoretical work)
• Pilot-scale steam explosion petreatment of lignocellulosic biomass for renewable chemicals production (collaboration with Bern University of Applied Sciences, 80% experimental /  20% theoretical work)

Contact: Dr. Thomas Pielhop

• Development of sensors for critical process parameters in (bio)process control (pH, pO2, biomass concentration, ion concentration, substrates and metabolites) based on electrochemical and optical methods and dielectric spectroscopy
• Application of sensors in on-line bioprocess monitoring and control, with a special focus on single-use systems
• Development of methods for near-line and off-line process analysis of metabolites and substrates in biotechnological cultivations (HPLC, spectroscopy, LC/MS)

Contact: Prof. Dr. Caspar Demuth

• From Medicinal Plant to Product: Quality assurance along the value chain of herbal medicines and other plant based health products in collaboration with our industry partners in Pharma, Food and Cosmetics
• Standardized extracts of the European Pharmacopoeia: Research contributing to rational and evidence-based phytotherapy
• Phytochemical Analysis: Analytical studies involving UHPLC-DAD-FLR-ELSD-RI-MS, GC-FID, HPTLC
• Bioautography: Bioassay-linked chromatography for pharmacological and toxicological screening of natural products
• Fractionation and isolation of plant-based natural products
• Galenic formulation: Forms of application including cremes, tablets, pastilles and liquid formulations for herbal drugs
• Ethnopharmacology: Research of traditionally used medicinal plants

Contact: Dr. Andreas Lardos

• Microbiology and metabolism of anaerobic fungi: laboratory work, microbiological & bioprocess oriented.
• Cultivation and kinetics of methanogenic archaea: Laboratory work, microbiological & bioprocess engineering oriented
• Detection and reduction of microplastics in soils: laboratory & field work, analytically oriented
• Power-2-Gas: Bioprocess engineering of microbiological methanation of hydrogen to methane. laboratory work, bioprocess oriented
• P-recovery from sewage sludge by means of hydrothermal carbonization: laboratory & pilot work, process engineering & analytically oriented.

Contact: Dr. Hajo Nägele

The research of the group cell physiology and cell engineering covers a broad spectrum of the field of cell biology with a focus on stem cell research, cell-based test systems/reporter systems, genetic engineering of cells and immunology (generation of new antibodies).

• Human induced pluripotent stem cells
  We have established the technology to produce human iPSCs in our laboratory in order to exploit the potential of iPSCs for the biotech industry. We can therefore help our industrial partners to develop applications of stem cell biology in the areas of: test systems based on stem cells, continuous supply of specialized cell types through targeted differentiation of iPSCs and identification and production of active substances from iPSCs.
• Development of cell-based test systems
  In cooperation with project partners, a large number of specially developed cell-based test systems and standard methods are used or, if necessary, newly developed. Some examples of these test systems include: blood-brain barrier, Caco-2 permeability test, osteoclast differentiation, cytotox assays, etc.
• Primary cell cultures and production of cell lines
  We identify, isolate and/or immortalize primary cells. These immortalized primary cells or already established cell lines can also be genetically modified (CRISPR/Cas) to change and improve their properties or adapt them for new applications. With the help of this technology, we can establish new cell-based assays (development of a full 3D skin model with a reporter system for oxidative stress), control recombinant protein expression in mammalian cells or develop new cells with new properties.
• Production of new antibodies against complex membrane proteins
  Many clinically relevant proteins such as G-protein coupled receptors or ion channels have a complex structure with multiple transmembrane domains. For this reason, purification of these proteins as a starting material for the production of specific antibodies is out of the question. Peptides used to generate AKs represent only a small fraction of the total protein and are not in the protein's native conformation, often resulting in lower affinity antibodies. Our method is based on using the entire human protein in its native conformation as an antigen for the production of high-affinity antibodies.

Contact: Prof. Dr. Jack Rohrer

• Cell morphology in thin-film preparations of whole blood
  Improper preparation of blood smears on slides for microscope examination can lead to distorted cell morphology of even damaged cells. Parameters such as ambient drying conditions, permitted shear forces, sample age etc have so far been empirically optimized in laboratory practices, but without a deeper understanding of the cell's membrane, nucleus and cytoplasm behavior during thin-film deposition and drying.
• Platelet activation in thin-film preparations of whole blood
  Pathways for the mechanical (& potentially chemical) activation of platelets in whole blood need to be investigated and proposed. Models can then be formulated and validated, which will capture the behavior of platelets during the creation and drying of whole blood wedge smears on slides for examination under a microscope.
• Investigation of whole blood surrogates and models
  The development of medical devices is heavily reliant on the supply of human samples. For certain central lab disciplines, whole blood is needed (can be expensive & of limited supply). A literature review of rheological and morphological characteristics of human blood can be conducted, in order to establish what alternatives / surrogates for human blood can be found, either artificial or natural (e.g. amongst domestic animal species).
• Engineering Macrophages for Cancer Immunotherapy
  We are looking for highly motivated person as MSc student for our project: "Engineering Macrophages for Cancer Immunotherapy". The master thesis is focused mainly on the molecular biology part of the project e.g. generation chimeric receptors and production of lentiviral vectors to express the receptors stably in human macrophages via transduction and evaluating the gene-engineered macrophages in in vitro. The desired profile is listed below. The project is related to "Human chimeric antigen receptor macrophages for cancer immunotherapy" (M. Klichinsky et al., 2020), but is a more sophisticated approach. You will learn state of the art cloning methods, how to produce lentiviral vectors for gene engineering and handling and transducing primary human cells. In addition we also want to evaluate non viral vectors for engineering. The methods for read out are using flow cytometry, microscopy, qPCR and Westernblot.
  Please note, the project is a high risk, high gain project, which, when it is successful, will be translated to a clinical application.
  The lab for the macrophage project is located at the USZ laboraties in Schlieren and you would be part of the macrophage team consisting of 3 people. You will be directly supervised by Dr. Sabrina Traxel and you will be able to take part in weekly group and project meetings, regular one-on-one discussions with supervisor, journal clubs and progress reports.

Contact: Prof. Dr. Steffi Lehmann