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Upcoming Seminars

Irene Bozzoni, M.Sc. - "From coding to no-coding RNAs and back"

Full Professor, Dept. of Biology and Biotechnology "Charles Darwin" Sapienza - University of Rome, Rome, Italy
When May 09, 2017
from 12:00 PM to 01:30 PM
Where tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Abstract
High-throughput transcriptome analysis has revealed that the mammalian genome is pervasively transcribed into many different complex families of RNAs; even among the polyadenylated species, half resulted to be non-protein-coding RNAs. Moreover, it has been recently shown that quite a considerable number of transcripts have an unusual circular form. These novel RNAs are emerging as crucial players in the control of differentiation and development and their deregulation has been linked to several inherited and acquired disorders. I will show how these new classes of transcripts impinge on muscle function in normal and disease conditions and how they control gene expression. 

Angelo Lombardo, M.Sc., Ph.D. - "Targeted Epigenome Editing for Therapeutic and Basic Applications"

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy
When Jun 06, 2017
from 12:00 PM to 01:30 PM
Where tigem Auditorium "Vesuvius"
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Contact Phone 081-19230659
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Abstract
Gene silencing by RNAi and artificial nucleases is a powerful approach to interrogate gene function and holds great therapeutic promise for several diseases. We have developed a novel modality of gene silencing that exploits endogenous epigenetic mechanisms of embryonic stem cells to convey robust and inheritable states of transcriptional repression at the desired target gene in somatic cells. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the desired target locus to instruct de novo DNA methylation. Silencing was sharply confined to the targeted gene, was resistant to exogenous activation and could be relieved by targeted DNA demethylation. We demonstrated the portability of this technology by silencing three highly transcribed genes and using multiple DNA binding platforms. Finally, we expanded the breadth of targeted epigenome editing by multiplex gene silencing within the same cell. Overall, our hit-and-run strategy may provide a powerful new alternative to conventional gene silencing for the treatment of several diseases.

Vincenzo Costanzo, M.D., Ph.D. - "DNA damage response and DNA repair in human biology and disease"

DNA metabolism laboratory, IFOM, Milan, Italy
When Jun 13, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
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Contact Phone 081-19230659
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Abstract
Over the years we have studied different aspects of ATM and ATR dependent DNA damage response and Rad51 mediated DNA repair. Using vertebrate cell free systems and more recently genetically tractable mammalian model systems we have uncovered basic biological responses to DNA damage promoting DNA repair during DNA replication. These findings will be discussed in light of recent results obtained in the lab. 

Ido Amit, Ph.D. - "The power of ONE: Immunology in the age of single cell genomics"

Immunology Department , Weizmann Institute of Science, Rehovot, Israel
When Jun 20, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
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Contact Phone 081-19230659
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Abstract
The power of ONE: Immunology in the age of single cell genomics Ido Amit Weizmann Institute of Science Immune cell functional diversity is critical for the generation of the different regulator and effector responses required to safeguard the host against a broad range of threats such as pathogens and cancer, but also from attacking its own healthy cells and tissues
In multi cellular organisms, dedicated regulatory circuits control cell-type diversity and responses.
The crosstalk and redundancies within these circuits and substantial cellular plasticity and heterogeneity pose a major research challenge.
Over the past few years, we have developed a collection of innovative single-cell technologies, which provide unprecedented opportunities to draw a more accurate picture of the various cell types and underlying regulatory circuits, including basic mechanisms, transitions from normal to disease states and response to therapies. I will discuss some of our discoveries and how they change the current dogma in immune regulation as well novel technologies that combine single cell RNA-seq with CRISPR pooled screens and demonstrate the power of these approach es to probe and infer the wiring of mammalian circuits, fundamental to future engineering of immune cells towards desired responses, including immunotherapy



Christian Behrends, M.Sc., Ph.D. - "Expanding the functions of autophagy regulators to the nucleus"

Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich (LMU), Munich, Germany
When Jun 27, 2017
from 12:00 PM to 01:30 PM
Where tigem Auditorium "Vesuvius"
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Contact Phone 081-19230659
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Abstract
Autophagy is an intracellular recycling and degradation pathway that depends on membrane trafficking. Rab GTPases are central for autophagy but their regulation especially through the activity of Rab GEFs remains largely elusive. We employed a RNAi screen simultaneously monitoring different populations of autophagosomes and identified 34 out of 186 Rab GTPase, GAP and GEF family members as potential autophagy regulators, amongst them SMCR8. SMCR8 uses overlapping binding regions to associate with C9ORF72 or with a C9ORF72-ULK1 kinase complex holo-assembly, which function in maturation and formation of autophagosomes, respectively. While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion. The latter phenotype involved association of SMCR8 with the ULK1 gene locus. Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2. Collectively, we established SMCR8 as multifaceted negative autophagy regulator.

Pietro Genovese, Ph.D. - "Towards Clinical Translation of Safe and Effective Hematopoietic Stem Cell Gene Editing for the Correction of SCID-X1 "

Gene transfer technologies and new gene therapy strategies, Unit San Raffaele -Telethon Institute for Gene Therapy (SR-TIGET) San Raffaele Scientific Institute IRCCS, Ospedale San Raffaele, Milano
When Jul 04, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
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Contact Phone 081-19230659
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Abstract
The scope of genetic engineering of hematopoietic stem/progenitor cells (HSPC) has broadened from gene replacement to genome editing using artificial nucleases, enabling precise modification of endogenous genes. We exploited this strategy on HSPC to insert a functional cDNA into IL2RG gene, whose mutations cause SCID-X1, thus restoring its function and physiologic expression while avoiding the risk of insertional mutagenesis. To support the rationale and explore the safety of gene correction we developed a mouse model carrying a mutated IL2RG gene in place of Il2rg. To evaluate efficacy and safety of hematopoietic reconstitution from a limited number of corrected HSPC we performed competitive transplant with WT and IL2RG-/- HSPC and found that 10% of WT cells fully reconstitute the lymphoid compartments and that administration of a conditioning regimen before HSPC infusion is required to protect from the risk of lymphoma development from the transplanted progenitors. To validate the gene correction strategy in the disease model we developed a gene editing protocol based on CRISPR/Cas9 on murine IL2RG-/- HSPC. Upon transplant, the gene corrected cells were able to generate functional B and T lymphoid lineages, showing a clear selective advantage over uncorrected cells. The corrected cells persisted long-term in the mice and generated a functional T cell response upon in vivo challenge with a pathogen, indicating that IL2RG edited cells are able to partially correct the disease phenotype. Furthermore, by optimizing the gene editing protocol for human HSPC we could attain the threshold of IL2RG editing required for safe and effective disease rescue. By combining donor DNA delivery by AAV6 and advanced generation ZFNs we measured ~35% HDR in the bulk treated CD34+ cells and ~13% HDR upon transplant in NSG mice. Deep sequencing performed on treated CD34+ proved the high specificity of our optimized ZFNs, with no significant modification at any of the off-target sites identified by GUIDE-Seq for earlier generation ZFNs. Finally, to establish a clinical ready protocol, we scaled up the process, treating up to 25 million cells with highly qualified reagents. These studies established safety and robustness of HSPC gene editing for SCID-X1 and will be instrumental for the design of the protocol for its first clinical testing.


Ayelet Erez, M.D., Ph.D. - "The role of aminoacids' metabolism in carcinogenesis"

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
When Jul 18, 2017
from 12:00 PM to 01:30 PM
Where tigem Auditorium "Vesuvius"
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Contact Phone 081-19230659
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Abstract
The urea cycle (UC) functions in the liver to convert toxic ammonia and nitrogen waste to urea. Clinically, patients with urea cycle disorders present mostly with hyperammonemia leading to acute and chronic neurological abnormalities.  Surprisingly, in contrast to the established role of the urea cycle enzymes in ureagenesis, the expression of most urea cycle proteins is dysregulated in multiple cancers for which the benefit is unknown. We find that UC proteins' dysregulation in cancers generates a novel pattern of mutations which increases cancer survival, proliferation, invasion and migration and is hence associated with worsened patients' survival across cancers. Thus, our studies reveal oncogenic metabolic rewiring that maximizes the use of nitrogen by cancer cells and has prognostic and diagnostic values.

Robin Ali, Ph.D. - "Gene therapy for retinal degeneration: rods, cones and rod-like cones"

Professor of Human Molecular Genetics, Division of Molecular Therapy, UCL Institute of Ophthalmology, London, UK
When Jul 25, 2017
from 12:00 PM to 01:30 PM
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Contact Phone 081-19230659
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Amit Nathwani, M.D. - Department of Haematology, University College London Cancer Institute, London, UK

When Sep 12, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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