Stem cells and genetic diseases

A.A. 2017/2018
Insegnamento per
6
Crediti massimi
48
Ore totali
Lingua
Inglese
Obiettivi formativi
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.

Struttura insegnamento e programma

Edizione attiva
Responsabile
Lezioni: 48 ore
Docente: Zuccato Chiara
Programma
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
Informazioni sul programma
Ppt files and scientific articles will be available on Ariel 2.0 WebSite
Prerequisiti e modalità di esame
Students are expected to have basic knowledge of developmental biology, molecular biology and genetic.
Oral examination.
Metodi didattici
Traditional frontal lesson
Materiale didattico e bibliografia
Tutorials ppt presentation and videos

Reference Material Scientific articles and reviews
Periodo
Secondo semestre
Periodo
Secondo semestre
Modalità di valutazione
Esame
Giudizio di valutazione
voto verbalizzato in trentesimi
Docente/i
Ricevimento:
Su appuntamento
INGM Padiglione Invernizzi Via F. Sforza 35, 20122 Milano