The course is focused on the steps that characterize the study of genetic diseases to identify new therapeutic strategies. I will discuss: i) how to study the function of genes related to diseases; ii) in vitro models to study genetic disease with a specific focus on those based on stem cells; iii) the strategies for the identification of pathogenic mechanisms; iv) pre-clinical studies in animal models ; v) clinical studies; vi) validation of new drug targets and the development of drug - screening assays; vii ) new therapeutic approaches based on gene therapy and stem cells.
Expected learning outcomes
At the end of the course students will have acquired knowledge about i) molecular tools and models to study disease genes; ii) strategies to identify and validate genetic-driven druggable targets; iii) the use of drug targets in drug screening assays; iv) the use of stem cells for understanding and treating genetic disorders; v) gene and cell-based therapies.
The study of gene function: genetic and molecular strategies (CRISPRs, TALENs, ZFNs); the Evo-Devo approach. In vitro models: immortalized cell lines, primary cultures and co-cultures; adult stem cells; hES and hiPS; stem cells differentiation into neural cell types using 2D and 3D methodologies; design CRISPRs for gene-editing of pluripotent stem cells. Ex vivo and in vivo models: isolating tissue and organ preparation; organotypic slice colture; small animal models (C. elegans, Drosophila melanogaster, zebrafish); transgenic mouse models; large animal models (transgenic pig, sheep and monkey). Molecular mechanisms of genetic disorders: the hypothesis-free approach: genomics, transcriptomics, proteomics, lipidomics; systems biology; the hypothesis-driven approach. Disease mechanisms and therapeutic targets: identification and validation of pharmacological targets: in vitro and in vivo studies; drug-screening assays. Studies in patients; biomarkers for early diagnosis, follow-up of the progression of the disease and monitoring of therapeutic responses; clinical trials. New therapeutic approaches and drug delivery strategies: RNAi as drugs; gene therapy; stem cell therapies; targeted drug delivery: nanoparticles, trojan horses and TAT-peptides.
Prerequisites for admission
The student must possess basic concepts of general pharmacology, biochemistry and molecular biology.
Interactive frontal lessons with Power-point-assisted slides and video; students are encouraged to attend and to actively participate; discussions are fostered to verify proper understanding, to stimulate critical thinking and to improve communication skills. Presented materials will be made available through the ARIEL platform.
Scientific articles and reviews will be provided. The students can also refer to "Stem Cell Genetics for Biomedical Research. Edited by Raul Delgado-Morales. Springer"
Assessment methods and Criteria
The exam consists of an oral test in which three topics (stem cells based models, drug development, pre-clinical assessment of drugs) are required to be covered.