Fatma Masmoudi is from Tunisia but born and raised in Kuwait. She received her BSc in Biochemistry and Molecular Biology from Kuwait University and her MSc on Biomedical and Molecular Sciences Research from King’s College London. Her MSc thesis was on isolated primary human hepatocytes encapsulated in alginate as a potentially new in vitro system for toxicological studies. During her MSc research project, she tested traditional two-dimensional (2D) and three-dimensional (3D) cell culture platforms using collagen and Matrigel, as opposed to the encapsulation in modified alginate in a 3D-form. Subsequently, she carried screening of cellular viability and function assays, and cytotoxicity assays. After completing her MSc, she had the opportunity to work at the University of Oxford with two research groups working on bone diseases. Throughout her research involvement, she continued working on tissue culturing and assay techniques to study osteoclasts formation and function. Following her interest in 3D culture platforms and drug testing, she is now doing her PhD on standardizing organoids for high-throughput screening (HTS) at Charles River who specialize in early drug discovery.
About Fatma’s research project
In recent years a variety of different methods have been used to grow organoids derived from either human multipotent adult stem cells or pluripotent stem cells (ESC, iPSC). Differences between protocols and approaches in organoids culture conditions have resulted in inconsistent results and lack of reproducibility. This calls for a more methodic approach to avoid human biological diversity so that studies are cross-comparable. The first aim of the project is to standardize organoids culturing methods and optimize human organoid culture for HTS. This will start with a secondment at the AMC where basic training will be provided on how to isolate stem cells from human fetal and adult intestines, culture organoids in 3D and epithelium monolayer form. Since the secondment is at the AMC Medical Microbiology department, virus culturing and compound testing as antivirals will also be practiced. After the secondment, knowledge and techniques on organoids and virus research will be transferred to Charles River to focus on developing intestinal organoids as a human 3D cell culture model for research on viruses. For many years virus studies have been hindered by the use of surrogate in vitro models that do not support viral growth and replication or by animal models that are often not compatible with an early drug discovery pipeline. As a direct follow up to the first aim, the standardized intestinal organoids culture will be used to study enteric viruses that infect the gastrointestinal (GI) tract. Following the successful development of gut organoids as a robust and reproducible ex vivo cultivation system for enteric viruses, drug screening on virus infected gut organoids with the aim of identifying a new class of antiviral drugs will be performed. The PhD project is conducted at Charles River early target discovery and validation site, allowing to get expertise on drug testing as antivirals in a high-throughput manner. To increase the knowledge on the introduction of HTS screening for antiviral drug testing on organoid platform, a secondment at the Rega Institute at KU Leuven will be included.
About Charles River
Charles River is an early-stage contract research organization (CRO). We have built upon our foundation of laboratory animal medicine and science to develop a diverse portfolio of discovery and safety assessment services, to support clients from target identification through preclinical development. Utilizing our broad portfolio of products and services enables our clients to create a more flexible drug development model, which reduces their costs, enhances their productivity and effectiveness to increase speed to market.
This project focuses on the application of human organoid technology in industrial drug discovery. The purpose of this project is to develop human organoid-based infectious disease models and to apply these in drug screening using a variety of technologies (e.g. (stem) cell culture, high throughput screening, virology/infectious disease, and high content imaging).