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Upcoming Seminars

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 Dec 19, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
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



Nicola Elvassore, Ph.D. - "High-Efficiency Cellular Reprogramming and Differentiation in engineered micro-environment"

Dipartimento di Ingegneria industriale, Università di Padova e Venetian Institute of Molecular Medicine (VIMM) di Padova
When Jan 16, 2018
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Abstract
Organogenesis and tissue generation are complex developmental processes starting from germ layer specification and phenotypic differentiation to tissue morphogenesis. This multi-scale processes are controlled by the concerted action of biochemical and physical cues, however the precise molecular events that integrate mechanical and biochemical signals to control developmental process are not fully known.
Biomimetic scale down of developmental processes through micro-technologies and microfluidics allows accurate control of cell culture microenvironment, of temporal evolution of chemical gradients and of mechanical features. Shaping topological, mechanical, and soluble microenvironment will allow investigating, characterizing, dissecting, and reconstructing biological and physiological phenomena. We explored whether we could control somatic human cell reprograming, pluripotent stem cell expansion, selective germ layer commitment and derivation of functional tissue-specific cells by tuning biomechanical and biochemical extrinsic and intrinsic cell signaling. The different developmental stages required cell niche specification in terms of accurate balance between extrinsic and intrinsic factors.

Diego Pasini, Ph.D. - "Control of Cellular Identity by Chromatin Modifying Activities"

Department Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy
When Jan 23, 2018
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
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Contact Phone 08119230659
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Establishing and then maintaining cellular identity during differentiation requires signalling events to be transmitted to the chromatin level; transcription factors (TFs) and chromatin-remodelling activities work together to orchestrate the transcription programs underlying this transmission. It is now clear that chromatin remodelers play a major role in regulating cellular identity, resulting one of the most mutated pathways among all type of human cancers. In this context, Polycomb proteins (PcG) play a crucial role as regulators in development and differentiation and are frequently mutated or altered in their activity in numerous types of human cancers, via molecular mechanisms that are still poorly understood. At the meeting will be presented the recent advances of our laboratory aimed to dissect the molecular mechanisms underling the activity of distinct PcG activities in establishing and maintaining cell type specific transcriptional identity during both normal homeostasis and pathological conditions.


Christian Michael Grimm, M.Sc., Ph.D. - "From mucolipidosis type IV to Ebola: insights into function and pharmacology of endolysosomal cation channels"

Ludwig-Maximilians-Universität (LMU), Department Pharmazie Center for Integrated Protein Science Munich (CIPSM), Munich, Germany
When Jan 29, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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My group is interested in the analysis of cation channels of the TRP (transient receptor potential) superfamily within the trafficking network of the endolysosomal system. Lysosomal dysfunction can result in endolysosomal storage disorders (LSDs) such as mucolipidoses or mucopolysaccharidoses but is also implicated in metabolic diseases, the development of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, retinal diseases and pigmentation disorders, trace metal deficiencies such as iron deficiency, and even cancer. Highly critical for the proper function of lysosomes, endosomes, and lysosome-related organelles (LROs) is the tight regulation of various fusion and fission processes and the regulation of proton and other cation concentrations within the endolysosomal system (ES). TRPML cation channels (TRPML1, 2 and 3) and Two-pore channels (TPCs) have recently emerged as important regulators of such processes within the ES and appear to be essential for a proper communication between the various endolysosomal vesicles. We use endolysosomal patch-clamp techniques, molecular and cell biology techniques as well as genetic mouse models to study the physiological roles and activation mechanisms of these ion channels in-depth.

Oscar Moran, Ph.D. - "Anion transport mechanisms through lipid bilayers by synthetic ionophores: towards a cystic fibrosis therapy"

Istituto di Biofisica, CNR, Genova, Italy
When Feb 06, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
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Abstract
Cystic fibrosis (CF) is a genetic lethal disease, originated from the defective function of the CFTR protein, a chloride and bicarbonate permeable transmembrane channel. CF mutations affect CFTR through a variety of molecular mechanisms which result in different functional defects. Current therapeutic approaches are targeted to specific groups of patients that share a common functional defect. We seek to develop an innovative therapeutic approach for the treatment of CF using anionophores, small molecules that facilitate the transmembrane transport of anions. We have characterised the mechanism of anion transport of synthetic molecules based on the structure of  prodigiosine, a red pigment produced by bacteria. Using ion sensitive electrodes (ISE), we measured the chloride eflux from large unilamelar liposomes upon addition of micromolar amounts of anionophores. Data is consistent with a carrier that facilitates the transport of anions  through lipid membranes down the electrochemical gradient. The transport is not coupled with proton or hydroxide translocations. The selectivity sequence of the prodigiosin inspired ionophores is formate > acetate > nitrate > chloride >  bicarbonate. Sulphate, phosphate, aspartate and gluconate are virtually not transported by these anionophores. The transport activity is modulated by the pH at the side where the anionophore is applied, suggesting that the ionization state of the molecule may decide the anion-anionophore interaction. These prodigiosin-derivate ionophores can also induce anion transport in living cells. Their capacity to transport chloride and bicarbonate when applied at low concentration, and  low toxicity take shape as a promising starting point for the development of CF-therapy drug candidates.

The project TAT-CF has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 667079

Angelo Reggiani, Ph.D. - "Glycogen synthase kinase 3β (GSK-3β): More on its role in neuropsychiatric and neurodevelopmental disorders

Department of Drug Discovery, Italian Institute of Technology (IIT), Genova, Italy
When Feb 20, 2018
from 12:00 PM to 01:30 PM
Where tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
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Abstract
Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation onto serine and threonine amino acid residues of several target molecules. The enzyme is part of the so called canonical Wnt signaling pathway, is highly conserved across species  and is involved in the regulation of many cellular processes such as cellular proliferation, migration, glucose regulation, and apoptosis. Because of this widespread role aberrant GSK-3β activity has been linked to several disease conditions such as inflammation, neurodegeneration, alteration of circadian clock, neurodevelopmental and psychiatric disorders.
In my talk I will initially focus on how dysregulation of GSK-3β activity can affect mood disorders and I will discuss the potential therapeutic benefit of specific GSK-3 β inhibitors.
Then I will move to discuss the role of GSK-3β in Fragile X syndrome (FXS) also known as Martin-Bell disease, one of the most common genetic causes of autism, due to an expansion of the CGG triplet repeat within the Fragile X mental retardation 1 (FMR1) gene on the X chromosome, resulting in loss of fragile X mental retardation protein (FMRP) expression.
There is now growing evidence of an increased GSK-3β activity in FXS. For example, in FXS animal models a GSK3b overactivation  has been found,  as also confirmed by us in cultured fibroblasts from FXS patients.  Furthermore, we and others have found that in FMR-1 mice the chronic administration of selective inhibitors fully normalizes typical FXS behavioral deficits such as hyperactivity, cognitive disruption and reduced social interaction. Taken together, these findings strongly indicate that GSK3b  is dysregulated in FXS and that  selective inhibitors should ultimately provide benefit to patients. 

Francesco Papaleo, Ph.D. - "A precision medicine genetic marker for core cognitive deficits in schizophrenia"

Genetics of Cognition Laboratory, Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), Genova, Italy
When Feb 27, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
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Contact Phone 08119230659
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Abstract
Antipsychotics are the first-line and most widely used medications for the treatment of schizophrenia spectrum disorders. Clinical responses to these drugs are highly variable. However, predictors of individual responses to antipsychotic treatments have been elusive. Here we report a pharmacogenetics interaction related to a core cognitive dysfunction in patients with schizophrenia. In particular, genetic variations reducing dysbindin-1 expression differentiate individuals with better executive functions responses to antipsychotic drugs. Multilevel ex vivo and in vivo analyses in post mortem human brains, genetically modified mice, andDrosophilae melanogaster demonstrated that such antipsychotics-by-dysbindin-1 interaction is mediated by enhanced presynaptic dopamine D2 function within the prefrontal cortex (PFC). These findings provide a genetic indicator for a biological mechanism underlying cognitive disabilities in patients with schizophrenia, thus paving the way for the implementation of a precision medicine approach to treatment.

Lukas A. Huber, M.D. - "Structure-function relationship of LAMTOR signaling on endosomes"

Biozentrum der Medizinischen Universität Innsbruck, Sektion für Zellbiologie, Innsbruck, Austria
When Mar 06, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
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Contact Phone 08119230659
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Abstract
The LAMTOR [late endosomal and lysosomal adaptor and MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) activator] complex, also known as "Ragulator," controls the activity of mTOR complex 1 (mTORC1) on the lysosome. The crystal structure of LAMTOR consists of two roadblock/LC7 domain-folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag guanosine triphosphatases (GTPases) associated with the pentamer through their carboxyl-terminal domains, predefining the orientation for interaction with mTORC1. In vitro reconstitution and experiments with site-directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling. Functional data validated the effect of two short LAMTOR1 amino acid regions in recruitment and stabilization of the Rag GTPases.