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.
The study of gene function - genetic and molecular strategies - the Evo-Devo approach
In vitro models: immortalized cell lines, primary cultures and co-cultures.
In vitro models based on stem cells - adult stem cells - introduction to hES and hiPS cell biology - the generation of induced pluripotent stem cells and their utility in disease modeling - differentiation of human induced pluripotent stem cells into neural cell types using the latest 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, knock-in and knock-out - 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
Pre-clinical research - pre-clinical drug trials in mice
Studies in patients - biomarkers for early diagnosis, follow-up of the progression of the disease and monitoring of therapeutic responses. - clinical trials - studies on post-mortem tissue
New therapeutic approaches and drug delivery strategy - RNAi as drugs - gene therapy - stem cell therapies - targeted drug delivery: nanoparticles, trojan horses and TAT-peptides.
Informazioni sul programma
Ppt files and scientific articles will be available on Ariel 2.0 WebSite
Prerequisiti e modalità di esame
Traditional frontal lesson
Materiale didattico e bibliografia
Tutorials Ppt presentation and videos
Reference Material Scientific articles and reviews