Discover Glo 2023 - Biologically Relevant Models to Advance your Research

Exploring Endogenous Cell Biology with CRISPR-Mediated Bioluminescent Tagging

Stably integrated transgenes and tags have been useful for interrogating basic aspects of cell biology, but often fail to fully reflect physiologically relevant parameters relating to binding partners and interactors. These known limitations may adversely skew data set interpretation. CRISPR-mediated methods now allow for specific and precise incorporation of tags into native loci (“knockins”), thus offering notable and incremental improvement in achieving true endogenous biology. This seminar describes our efforts to improve gene editing efficiencies and workflows, means to identify and characterize those edits, and to demonstrate their utility using well-validated cancer pathway protein:protein interactions. Specific emphasis will be focused on our luciferase and luciferase complementation tagging systems and the relative merits or limitations of each approach.

A transgenic mouse model for multi-scale visualization of stress activation

Cells are continuously exposed to microenvironmental stressors. The ensuing adaptive response relies on various molecular sensors that activate signaling pathways governing transcriptional and translational programs. These programs then support cellular plasticity in the face of stress. The integrated stress response (ISR) axis represents a major signaling pathway controlling various cellular functions involved in cellular plasticity. However, the inducibility of ISR is heterogeneous within the organism and rather tissue and cell type specific. Thus, the study of how the different cells comprising the tissue of interest respond to stress requires models that can track the degree of activation of stress pathways at all scales of the organism. To address this issue, we have developed a transgenic mouse model that allows the visualization of ISR activity at the organism, tissue and cell level. To illustrate the interest of this technology based on bioluminescence acquisition, our results show how stem or differentiated epithelial cells differentially induce ISR following proteostasis stress in derived intestinal organoids. Overall, this transgenic model is an interesting resource to monitor and study the degree of stress activation and reduce the use of animals in preclinical studies.

From Petri Dishes to Chips: How Biochemical Assays Enhance Organ-on-Chip Technology

The successful translation of pre-clinical research results into clinical practice remains a significant challenge for the pharmaceutical industry. Clinical trials often fail, have limited efficacy, or induce toxic side effects that were not anticipated. This is in part due to inadequate pre-clinical models, such as two-dimensional cell cultures, which do not mimic the complex environment cells find in vivo. Recent advances in organ-on-a-chip technology offer a promising avenue to model important aspects of human physiology in vitro. MIMETAS' OrganoPlate® is an organ-on-a-chip platform that allows for controlled and complex cultivation of cellular systems in three dimensions, mimicking architecture, mechanical properties, cellular composition and biochemical functionalities of healthy and diseased organs. To effectively harness the potential of this technology, sensitive, robust, reproducible, and interpretable assays are necessary for the study of complex tissue cultures. These assays must be able to accurately measure key physiological parameters and responses to treatments, allowing for the identification of potential drug candidates and the prediction of clinical outcomes. The integration of organ-on-a-chip technology and reliable assays could transform pre-clinical drug development by providing accurate and predictive models of human physiology.

I grew up in Southern Switzerland and relocated to Zurich in 2012 to commence my undergraduate studies in Biology at the Swiss Federal Institute of Technology (ETH). Subsequently, I pursued a Master's degree in Biomedical Engineering, with a specialization in tissue engineering, also at ETH, and successfully completed my studies in 2018.

From 2019, I have been a Marie Sklodowska-Curie fellow student affiliated with MIMETAS, a biotech company located in Leiden, Netherlands, as part of the PoLiMeR consortium. In my current role, I focus on liver models and contribute to the development of a throughput-capable organ-on-chip culture platform, which MIMETAS specializes in developing and commercializing.