The TIGEM Community

• Funded by the Italian Telethon Foundation
• Scientific Director, Andrea Ballabio
• 12 group leaders
• 35 technicians, administrative and support staff
• 51 PostDocs and research fellows
• 40 Ph.D. students
• 14 undergraduate students

Areas of Basic Interdisciplinary Research

• protein biochemistry
• molecular, cell and developmental biology
• molecular genetics
• bioinformatics
• functional genomics
• systems and synthetic biology
• gene therapy

Research Programmes

• Cell biology of genetic diseases
• Systems biology and Functional genomics
• Molecular therapy

Selected Research Projects Under Study

• Cilia and Human Diseases: Insights from the OFD Type I Syndrome
• Gene Therapy Approaches to Cure Patients with Inherited Blindness Diseases
• Gene Therapy of Severe Inherited Photoreceptor Diseases due to Mutations in Large Genes
• Hepatocyte Gene Therapy

• Lysosomal Storage Disorders: From Mechanisms to Cure
• Membrane Traffic and Neurodegeneration in Lysosomal Storage Disorders
• Mendelian Disorders of Membrane Trafficking: Molecular Mechanisms and Drug Target Identification

• Organization and Regulation of Intracellular Membrane Transport in Health and Disease
• Pharmacological Chaperone Therapy for the Treatment of Lysosomal Storage Disorders

• Role of Membrane Trafficking in Copper Homeostasis
• Systems and Synthetic Biology
• Substrate Reduction Therapy for the Treatment of Lysosomal Storage Disorders
• The Role of Noncoding RNAs in Eye Function and Disease
• Towards a Clinical Trial of Gene Therapy for Mucopolysaccharidosis VI
• Treating Retinal Degeneration by Transcriptional Silencing

Major Scientific Achievements

• Identified the disease genes responsible of several rare genetic disorders including: Oral- facial-digital type I (OFD1) syndrome, Multiple Sulfatase Deficiency (MSD), Opitz syndrome, X-linked recessive Chondrodysplasia Punctata and Ocular Albinism, among others

• Participated to the first clinical trial for Leber congenital amaurosis
• Demonstrated that a block of autophagy is involved in the pathogenesis of lysosomal storage disorders
• Demonstrated that large genes can be packaged in certain sero-types of adeno-associated viral vectors
• Developed novel reverse-engineering algorythms and modelling assessments in systems and synthetic biology
• Devised a bioinformatic strategy to identify target genes of microRNAs more efficiently
• Discovered that lysosomal biogenesis and function is regulated by a gene network that responds to a “control room” for lysosomes
• Coordinated the generation of the first high-resolution expression atlas of the mouse embryo transcriptome
• Demonstrated that transcriptional activation of lysosomal exocytosis promotes cellular clearance
• Successfully used adeno-associated viral vectors in several pre-clinical studies on lysosomal storage disorders including MPS II, MPS IIIA, MPS VI and MSD and in vast series of animal models of retinal degenerations including Ocular Albinism, retinitis pigmentosa, Stargardt disease, and Leber congenital amaurosis
• Developed a method to predict drug mode of action and drug repositioning from transcriptional responses
• Discovered that the transcription factor EB (TFEB) links autophagy to lysosomal biogenesis

Funding

• Other than by the Telethon Foundation, TIGEM is funded by prestigious international funding agencies such as the EU, NIH, EMBO and the Wellcome Trust, among others
• TIGEM has played a leading role in EU funded research and has been part of 12 EU funded consortia, three of which have been coordinated and managed by TIGEM. In addition, TIGEM has been awarded an advanced (CLEAR) and a starting (RetGenTx) European Research Council (ERC) grant as well as two Marie Curie Actions for the promotion and career development of young investigators