The aim of the course is to address the phases that characterize the study of a genetic disease for the identification of therapeutic strategies. It will discuss (i) stem cells as new models for understanding the function and dysfunction of disease genes; (ii) strategies for the identification of pathogenetic mechanisms; (iii) pre-clinical studies in animal models; (iv) studies in the patient; (v) the validation of new pharmacological targets and the development of drug-screening assays; (vi) novel therapeutic approaches based on gene therapy and stem cells.
1. In vitro models for the study of genetic diseases - Immortalized cell lines (constitutive and inducible knock-in and knock-out lines), primary cultures and co-cultures. - In vitro models based on stem cells adult stem cells mouse and human ES cell lines: derivation, culture, differentiation and genetic manipulation human iPS cells 2D and 3D differentiation protocols direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders - Single cell based strategies for the acquisition of transcriptional and epigenetic information in stem cells and in vivo - Stem cells for the study of protein structure, function and evolution
2. Ex vivo and in vivo models - isolated tissue and organ preparation to quantify the physiological (phenotypical) effects of disease genes - small animal models (C. elegans, Drosophila melanogaster, zebrafish) - transgenic mouse models, knock-in and knock-out - large animal models (transgenic pig, sheep and monkey)
3. Molecular mechanisms of genetic disorders - hypothesis-free approach and systems biology - the hypothesis-driven approach - high-throughput genotyping and sequencing for the study of genetic diseases
4. Disease mechanisms and therapeutic targets - identification and validation of pharmacological targets: in vitro and in vivo studies - drug-screening assays
5. Pre-clinical research - pre-clinical drug trials in mice - drug delivery in mice (acute and chronic studies) - assays to monitor drug efficacy
6. Studies in patients - genetic test and pre-implantation genetic diagnosis (PGD) for monogenic diseases - genome-wide association study (GWA study, or GWAS) for the identification of modifiers gene in monogenic diseases - biomarkers for early diagnosis, follow-up of the progression of the disease and monitoring of therapeutic responses. - clinical trials
7. New therapeutic approaches and drug delivery strategy - gene therapy for monogenic diseases - therapies with adult stem cells - stem cell therapies in Parkinson's Disease - targeted drug delivery: nanoparticles, trojan horses and TAT-peptides
8. Special lessons - good laboratory practice - the scientific manuscript - research funding - fraud and misconduct - science communication
Tutorials ppt presentation and videos
Reference Material Scientific articles and reviews
Prerequisites and examination procedures Students are expected to have basic knowledge of developmental biology, molecular biology and genetic. Oral examination.
Teaching Methods Traditional frontal lesson
Language of instruction English
Recommended Prerequisites none
Program information Ppt files and scientific articles will be available on Ariel 2.0 WebSite