Medical products, drugs and chemicals are often being tested for their cytotoxicity to determine the risk they might have on humans and on the environment. The bio-compatibility of substances is of special interest for the group of cell physiology and cellular engineering. We perform a cytotoxicity standard assay routinely in vitro on a broad range of different cell lines.
The assessments of the in vitro cytotoxicity assays on cell cultures are based on the preparation of the tested materials. The preparation is then applied to the standardized cytotoxicity assay. The quantification of cell growth is performed by a colorimetric assay (MTT). A toxic effect of the applied substances is assessed by the fitting of a dose-response curve to the growth of the cells to the concentration of applied substance. Furthermore the inhibitory effect can be calculated by the IC50-value, the inhibitory concentration where the growth of cells is reduced to 50% of the control. The results are then finally summarized in a report. 

Many clinically relevant proteins such as G-protein coupled receptors (GPCRs) or ion channels have a complex structure with multiple membrane spanning regions. Therefore purification of the proteins as a source of antigen to raise specific antibodies is not feasible. Peptides representing a very small fraction of the protein of interest are not in the native conformation and often lead to lower affinity antibodies. Our method relies on the fact that the full-length human protein in its native conformation is used as an antigen which results in the generation of high affinity antibodies. Additionally, we use rabbits for the immunization since it is known that rabbits produce in general higher affinity antibodies than mice which also helps to generate excellent antibodies. 
 

Pluripotent stem cells have an essential role in embryonic development as well as in tissue and organ homeostasis during the entire life of an organism. Understanding the biology of this outstanding kind of cell could provide the biotechnology industry with game-changing opportunities. Experts in regenerative medicine currently investigate possibilities to develop new organs or parts thereof using stem cells. On the other hand the cosmetic industry is strongly interested in the rejuvenation and regeneration potential for skin that this type of cells could provide. However work with stem cells is impaired by their natural scarcity as well as the technical and ethical difficulties to collect and cultivate them.

These obstacles were resolved in 2007 when Takahashi and colleagues showed that simple skin cells could be artificially induced into pluripotent stem cells. The pluripotency of those induced pluripotent stem cells (iPSCs) is best demonstrated by their ability, like a natural embryonic stem cell, to form viable mouse chimeras.

We established the technology to generate iPSCs at the ZHAW in order to bring the full potential of pluripotent stem cells to the biotechnology industry. The group of cell physiology and cellular engineering can therefore help its partners to develop applications based on stem cell biology such as: 

• Test systems based on stem cells 
• A steady supply of specialized cell types through targeted differentiation of iPSCs 
• The identification and/or preparation of active ingredients from iPSCs

The molecular mechanisms of the cell physiology are often the basis for the understanding of essential processes in industrial biotechnology. Therefore the knowledge of the functional interactions within the cells and between the cells are the basis for the optimization of biotechnological processes or for the manufacture of products. Examples include changing an intracellular or membrane protein in a way that it is secreted by the cells for easier purification or changing the intracellular localization of an enzyme to use its activity for example as a membrane protein at the plasma membrane of special cells or to prevent wrong glycosylation of proteins which might be dangerous (uptake of the protein by dendritic cells and macrophages and creating an immune response) if used as a drug in humans. 

For projects in the area of glycobiology the intracellular transport and the correct localization of glycosyl transferases is determined as well as their enzymatic activity. The precise knowledge of the pathways allows a manipulation of the final localization of the glycosyl transferases for biotechnological use such as a secretion of the enzymes for easier purification. We also analyze the effect of differences in glycosylation of biosimilars (drugs, follow-on biologic, mostly a protein). The glycosylation of a protein as a hallmark of its quality, can vary during the production of recombinant proteins from producer to producer but also from batch to batch. This can lead to differences in the activity but also inherit the potential danger that the immune system of a patient will produce antibodies against those proteins used as drugs. In the best case such an immune reaction would render the drugs useless but unfortunately there is the danger that it will start an auto immune reaction. 

The laboratory of cell physiology and cell engineering manages a 4-lasers FACS (fluorescent activated cell sorter) that enables the precise analysis of physical or chemical characteristics of heterogeneous cell mixtures. Using the FACS we can identify rare cell types in a larger cell population (e.g. mesenchymal stem cells from adipose tissues), immuno-genotype cells (e.g. peripheral white blood cells), monitor cell differentiation (e.g. differentiation of macrophages to osteoclasts) or detect subtle changes in cellular physiology. Our flow cytometer is also equipped with an electrostatic sorting module that enable the enrichment of a specific cell type from a complex cell mixture or the sorting of a single cells into 96 well plates to generate a new clonal population.