Cell Biology Webinar Series

Abstract:

Classifying tumors by organ, such as breast or brain, ignores the genetic, biologic, and patient-related factors that make cancer cases unique. Cancer therapy is therefore moving from a one-size-fits-all paradigm to one of greater personalization. Using an in-house established platform, based on an assembly of benchtop instruments, researchers in the Remke Lab at the University of Dusseldorf Medical School have developed a system that will help guiding oncologists toward the right treatments, at the right time, for the right patients.

Based on quantitative, high-throughput screening, this approach will contribute to uncover optimal treatment choices from libraries of approved and late development-stage anticancer drugs. This highly sensitive, cell-based screening platform allows low-volume, multiple-concentration assays to support informed decision-making. The ultimate goal of this research is to enable truly personalized treatment regimens for life-threatening cancers.

Speaker Bio:

Dependable, creative, and capable scientists, Nan Qin and her colleagues, have developed a semi-automated high-throughput drug screening platform in the Department for Pediatric Oncology, Hematology and Clinical Immunology at the Children’s Clinic of the University Hospital in Düsseldorf.

In the past 5 years, they have successfully screened more than 100 primary cultures of patient-derived tumor cells and more than 150 established cell lines from a wide variety of tumor entities using drug libraries comprising about 250-650 compounds. They have extensive experience in sample preparation and processing of in vitro high-throughput drug screening and evaluation and annotation of the corresponding data.

Abstract:

The high rates of clinical failure of new anticancer drugs highlight that the standard approaches to evaluate drug efficacy do not faithfully reproduce human biology, and thus, do not accurately represent the disease processes or response to treatment. In this webinar we will discuss the advantages of using 3D culture models over the traditional methods, with particular emphasis on the importance of tumor microenvironment and tissue-relevant extracellular matrix (ECM) in obtaining accurate drug response data. We will show examples of tumor-specific 3D culture models and their use for screening of anticancer compounds, including immuno-oncology agents. Finally, we will highlight the advantages of using multimodal readout to evaluate multiple parameters associated with cellular response to anticancer drugs.

Learning objectives:

• Learn about the fundamental differences between conventional 2D and 3D cell culture approaches and the pros and cons of using them for drug development.
• Learn how tumor microenvironment affects tissue organization and response to treatment and why it is crucial to incorporate it into pre-clinical models.
• Discover how Tecan’s D300e and Spark Cyto can be used to analyze drug response in 3D cultures.

Speaker Bio:

Julia has over 20 years of experience in oncology R&D spanning multiple areas of cancer biology, including: the development of organotypic preclinical models, molecular target and biomarker discovery, evaluation of drug-resistance, tumor microenvironment, cancer stem cells, and tumor immunology. Prior to founding zPREDICTA, Julia held a faculty appointment at the Department of Biological Sciences at Purdue University working on the mechanisms of cancer development and spread and the effects of tissue microenvironment on drug response. Subsequently, Julia founded zPREDICTA with a goal to develop tumor-specific 3D culture models reconstructing the native microenvironment of human tissues to mimic the drug behavior as seen in patients. From target discovery and lead optimization to preclinical evaluation of efficacy and toxicity, zPREDICTA’s goal is to develop the tools necessary to accurately identify compounds that will have the highest probability of improving human health.

Abstract:

Organotypic cultures are well established in research but are mainly manually processed. In order to implement these technologies in industry, the method standardization using liquid-handling platforms to automate production processes is mandatory. We will present some key examples of production and maintenance of scaffold-free and scaffold-based 3D cell cultures in comparison to manual handling. Cultures based on tumor cell lines (HCT-116) and human fibroblasts (WI-38) were produced in a high throughput-compatible 96 well plate format, which makes them amenable for drug screening.

Speaker Bio:

Dr Epifania Bono is a research associate in the Cell Biology and Tissue Engineering team at ZHAW in Waedenswil. She completed her degree in biology, specializing in molecular biology, at the University of Palermo in Italy. During her PhD, Epifania focused on cell biology and molecular biology at the University of Palermo, and then worked at the Institute of Biomedicine and Molecular Immunology ‘A.Monroy’ in Palermo. Her current scientific research focuses on cell culture technology, tissue engineering, and bioprinting for the development and application of biomaterials, as well as cell and tissue characterization in manual and automated cultivation systems.

Abstract:

Metabolic profiling of cell line collections has become an invaluable tool to study disease etiology, drug modes of action and to select personalized treatments. However, large-scale in vitro dynamic metabolic profiling is limited by time-consuming sampling and complex measurement procedures. By combining high-throughput metabolomics with time lapse microscopy we established a workflow for large-scale metabolic profiling of adherent mammalian cells and the rapid measurement and analysis of drug-induced dynamic changes in intracellular metabolites. I will illustrate how this technology enables to study the role of aberrant transcriptional regulation in mediating cancer metabolic rewiring and can be applied to reveal drug mechanism of action. Our approach opens new opportunity in systems pharmacology and reveals new ways to analyze patient-derived metabolic profiles and the development of alternative therapeutic strategies to counteract upstream reprogramming of cellular metabolism.

Speaker Bio:

Mattia Zampieri is a junior PI at the Institute of Molecular Systems Biology of ETH in Zurich. He studied Bioengineering in Padova before doing a PhD in Bioinformatics at the International School for Advanced Studies in Trieste and Boston University. During his PhD he worked on mathematical modeling of microbial metabolism and reverse engineering transcriptional regulatory network from molecular profiling data. In 2011 he moved to the lab of Prof. Uwe Sauer at ETH where he developed novel high throughput metabolomics frameworks and quantitative models to study the role of microbial metabolism in mediating the response to antimicrobial treatments. His research led to unique high-throughput metabolomics frameworks and computational tools broadly applicable to diverse biological systems and therapeutic areas, opening new opportunities in systems biology and systems pharmacology.

Abstract:

High-content screening and morphological profiling is becoming increasingly popular in the characterization of new compounds and their mode of action in pharmaceutical and academic drug development. Using highly sensitive technologies, morphological changes can already be detected in sub-cytotoxic concentrations. For the generation of morphological profiles, a precise investigation of cytotoxicity with respect to concentration and time is therefore indispensable. In this webinar, Dr. Christopher Wolff, FMP Berlin, presents a fast and reliable method to develop a cytotoxicity assay for high-content screening using Tecan’s Spark® Cyto multimode reader with imaging capabilities. The imaging-based apoptosis assay enables a precise determination of the apoptotic state in treated cells. The Spark® Cyto provides highly sensitive and precise characterization of compound-induced cytotoxicity, while multicolor image analysis allows for rapid and reliable detection of early and late apoptotic cells. The assay performance was found to be comparable to dedicated high-content screening imagers, enabling a rapid integration of this assay into large-scale high-content screens.

Speaker Bio:

Dr. Christopher Wolff is a biophysicist and member of the screening unit of the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP). With his expertise in quantitative analysis of multicolor microscopy images, he is working on expanding the analytical methods of the screening unit in the field of high-content screenings. In particular, he focuses on the morphological profiling of large compound databases to characterize the toxicity and mode-of-action of uncategorized substances to assist in the development and discovery of new therapeutic agents.

Abstract:

The Murdoch Children’s Research Institute (MCRI) is Australia’s leading center for pluripotent stem cell-based medicine and is internationally recognized for its expertise in disease modeling. Our strategy is to apply this world-leading expertise in stem cell-derived tissues via the development of a robust pipeline for human-targeted drug discovery. By modeling a ‘disease in a dish’, we are able to understand disease mechanism-of-action and test clinically validated drug targets. To achieve this, MCRI has established a Disease Modelling Facility designed for automated high content-high throughput, drug screening of compounds using human-derived cells and tissues.

Speaker Bio:

Hidalgo-Gonzalez has over 10 years' experience in the generation of genetic and induced disease models from human induced pluripotent stem cells designed for high-throughput drug screening. Hidalgo-Gonzalez is the Manager of the Disease Modelling Facility at MCRI. His research focuses on the identification of novel drug-like compounds in advanced human disease models. This facility is equipped with an automated high-throughput imaging system for monolayer and 3D phenotypic drug screening.

Abstract:

Most organisms display ~24-hour cycles in their biology. In humans and other animals, these circadian rhythms result from daily timing mechanisms in every cell that together function like a biological clock; allowing our physiology to anticipate and prepare for the differing demands of day and night. Normally our biological clock is fine-tuned each day by the schedule we keep, particularly the timing of meals and light exposure. When we see bright light or eat at the wrong biological time, as often occurs during shift work or jet-lag, it disrupts our biological clock and increases the risk of chronic illnesses such as type II diabetes, cardiovascular disease and some cancers. Conversely, the effectiveness of some drugs and surgeries can vary with the biological time of treatment. Delineating the molecular mechanisms that impart daily rhythms to our biology is therefore important for understanding human health and may provide new insights into the prevention and treatment of many diseases. Our research is focused on understanding the fundamental mechanisms of daily cellular timekeeping and how circadian regulation of biological function is achieved.

Speaker Bio:

John studied Biochemistry at New College, Oxford, and then did his PhD research on cAMP signalling and the mammalian circadian pacemaker at the MRC Laboratory of Molecular Biology in Cambridge with Michael Hastings. As a post-doc, he studied circadian rhythms in plants and algae with Andrew Millar (Edinburgh) and then human cells then at the Institute of Metabolic Science in Cambridge. John was awarded a Wellcome Trust Career Development Fellowship in 2011, and in 2013 was recruited to become a group leader in the Cell Biology Division of the LMB.

Abstract:

Photodynamic therapy (PDT) is a therapeutic strategy based on the selective accumulation of a photosensitizers (PS) and their activation by light to induce cytotoxic death in cancer cells. This approach has been introduced into the clinics several years ago and is currently routinely used for the treatment of various types of cancer, particularly cutaneous malignancies. Although PDT is associated with excellent cosmetic results, specificity towards cancer cells, insufficient PDT efficacy and side effects including inflammation induced pain constitute major challenges associated with this treatment. Identification of novel photosensitizer molecules, potentially activated by daylight, associated with decreased PDT-induced pain and inflammation, as well as the development of novel, tumor-targeted PS delivery systems are gaining increasing interest in the field. Our group is working on both aspects: using the Tecan Spark20M reader we are currently i) characterizing novel photosensitizer molecules with regard to their uptake and daylight-induced PDT efficacy in skin cancer or their progenitor cells, ii) assessing novel nanocarrier systems including functionalized extracellular vesicles (EVs) for tumor-specific and highly efficacious PS delivery. In this presentation, we will explain the basic protocols which we have established and discuss experimental results from our PS uptake and PDT induced cellular cytotoxicity studies.

Speaker Bio:

Dr. Ina Albert is scientist in the Pharmaceutical technology and Pharmacology group at Zurich University of Applied Science (ZHAW) Waedenswil in Switzerland. She works on the development of cell based in vitro assays to characterize innovative treatment strategies against cancer. Prior to joining ZHAW, she studied Pharma-Biotechnology at Ernst-Abbe-University in Jena

Abstract:

Routine applications in cell-biology laboratories include the labor intensive work of clone selection and picking for a diversity of downstream applications. Hybridoma clone picking for isolation and screening of monoclonal antibodies as well as stem-cell clone picking are becoming a growing need of pharma and research labs. In this presentation we will show how SciRobotics PickoloPLUS™ and GFPickolo solutions on Tecan’s Fluent™ are used for automating the task of hybridoma and stem-cell clones picking.

Speaker Bio:

SciRobotics designs and develops computer vision based solutions for laboratory automation in the biopharma industry, academia and governmental institutes. Dr. Kaplan is a scientist and entrepreneur with an interdisciplinary background in Software Engineering and a PhD in biology from the Weizmann Institute of Science in Israel. Prior to co-founding SciRobotics, he worked as a software engineer at Intel and at a startup company in the silicon valley in California.

Abstract:

Determining if a new cosmetic product, pharmaceutical ingredient, or chemical substance is harmful to humans is a key prerequisite for product safety and consumer protection. Traditionally, skin sensitization testing relied on animal models, but these approaches are expensive, time consuming and raise ethical questions, while only offering limited human relevance and accuracy. SenzaGen has developed a unique, in vitro approach to sensitization testing, combining cell biology and flow cytometry with genomics-based screening and machine learning-assisted classifications

Speaker Bio:

Anna Chérouvrier Hansson leads the business development and sales activities at SenzaGen. With more than 20 years in the life science industry, she has experience from leading projects within pharma, medical device and specialised service companies with focus on delivering superior products and solutions.

Ulrika Mattson is Senior Application Scientist at SenzaGen. She has a long experience of laboratory work and today she leads projects and studies involving SenzaGen’s proprietary technology GARD for assessment of skin and respiratory sensitizers. Ulrika has experience of Tecan’s equipment at SenzaGen’s laboratory.

Abstract:

Pharmaceutical development, fundamental molecular and cellular biology research, as well as biologics manufacturing rely on genetically engineered cell lines to induce a well-defined phenotype. However, in conventional cell line development workflows, obtaining a stable monoclonal cell line can be a tedious process of several weeks with extensive manual work, but often of limited success. Discover how the FluidFM BIO Series remarkably speeds up the generation of genetically engineered monoclonal cell lines. The FluidFM cell line development workflow combines two unique features - automated nano-injection for the transfection and pick & place for cell isolation. In this webinar, we will introduce you to the benefits of FluidFM and show you how:

• Automated FluidFM nano-injection optimizes CRISPR-Cas9 RNP delivery, directly into the nucleus.
• FluidFM pick & place enables gentle single cell isolation to start a monoclonal cell culture.
• FluidFM cell line development workflow is particularly suited for hard-to-transfect cells, rare cells, large inserts, and multiplex editing.

With FluidFM, get your monoclonal cell line in less than 3 weeks.

Speaker Bio:

Dr. Paul Monnier obtained his PhD in molecular biology from University Pierre and Marie Curie in Paris, while working on non-coding RNAs involved in epigenetic growth control of the embryo. After a postdoc at ETH Zurich, working on CRISPR genetic screens, he joined Cytosurge to set up their new biology laboratory. Here, he develops applications and protocols related to FluidFM technology in the field of Life Sciences.

Abstract:

In vitro functional bioassays are central to potency and stability testing programs for drug release, but require a high degree of precision and accuracy between experiments and operators. Automating these assays can increase throughput, reduce assay variability, decrease operational costs, and more importantly offer consistent method execution and transfer between sites. In this webinar we present automation of functional cell-based assays from Eurofins DiscoverX using Tecan’s newest generation of liquid handler, FLUENT. Case studies on automating DiscoverX’s cell-based assays that are routinely used for drug release will be discussed.

3 key words on the content:

Automation
Potency Bioassay
QC Lot Release

Speaker Bio:

Gaurav earned his Ph.D. in Cell and Molecular Biology from the Indian Institute of Science studying the activation mechanism of GPCRs. During his post-doc at the University of California San Diego, Gaurav discovered novel intracellular trafficking pathways essential for organelle biogenesis. At Eurofins DiscoverX, Gaurav is responsible for scientific integration and market development of the cell-based assays portfolio, and support method transfers to CROs for drug development programs for biologics and biosimilars.

Dr. Lucía Bruzzone is a product manager at Tecan. She studied molecular biology and biotechnology at the University of Buenos Aires in Argentina. During her PhD, she focused on cell biology and genetics at the Institut Jacques Monod in Paris, France. She joined Tecan in 2019 as an application specialist and focused on the development and support of applications on Tecan’s liquid handling platforms in the cellomics and proteomics area before joining the detection team in 2021.

Abstract:

The Fraunhofer ITMP ScreeningPort in Hamburg focusses on assay development for biochemical and cell-based formats, on development and application of efficacy and toxicity assays based on human pluripotent stem cells, on assay miniaturization, high-throughput and high-content screening, and on chemi- and bioinformatics. During this webinar hIPSC assay technologies will be presented that are being applied and developed further at the ScreeningPort to address questions in current drug discovery projects. The presenters will share their view on the emerging need for assay standardization and increased throughput, as well as address the challenges that are faced during lab automation.

3 key words on the content:

HiPSC
Drug discovery
Lab automation

Speaker Bio:

Dr. Ole Pless is a senior scientist at Fraunhofer ITMP ScreeningPort in Hamburg, Germany, focusing on the application of pluripotent stem cell technology for efficacy and safety assessment of therapeutic candidate molecules. Dr. Pless has leading roles in several pan-European research consortia focusing on neurodegenerative, metabolic and infectious disease. Dr. Pless holds a PhD from the Max Delbrück Center for Molecular Medicine and the Humboldt University in Berlin.

Gesa Witt is a research associate at the Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP). She studied Pharmaceutical Biotechnology at the University of Applied Sciences in Hamburg and joined Fraunhofer in 2014. Her scientific work focusses on the development of lab automation solutions for biochemical and cell-based assays as well as on the implementation of appropriate research data management workflows.

Abstract:

The outcomes of cell-based workflows - such as transfection, cell proliferation and cell-based assays - can be affected by factors as varied as genetic design, media composition and process factors. Given limited time and resources, how would you narrow down which conditions give you the best outcomes? Design of Experiments (DOE) is an efficient approach to optimizing such complex biological processes.

In this presentation, we will demonstrate the use of our Antha software to easily plan and implement automated DOE for a range of cell biology processes. In particular, we will walk through a multi-stage DOE that we executed to achieve an 500% increase in product yield by optimizing growth medium components and process factors. We will then show how this methodology was easily adapted for the optimization of transfection and construct assembly. The outcomes of cell-based workflows - such as transfection, cell proliferation and cell-based assays - can be affected by factors as varied as genetic design, media composition and process factors. Given limited time and resources, how would you narrow down which conditions give you the best outcomes? Design of Experiments (DOE) is an efficient approach to optimizing such complex biological processes.

Speaker Bio:

Dr James Arpino is Principal Scientist and Product Manager for DOE at Synthace. James is passionate about realising the breadth of improved productivity afforded by lab automation platforms and implementation of highly sophisticated DOE. James holds a PhD in Synthetic Biology and Protein Engineering and has almost 10 years’ experience as a research scientist.