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Upcoming Seminars

Serena Carra, M.Sc., Ph.D. - "The HSPB8-BAG3-HSP70 chaperone complex: implication in protein homeostasis and neurodegenerative diseases"

University of Modena and Reggio Emilia, Modena, Italy
When Dec 12, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Abstract
HSPB8 is a member of the mammalian small Heat Shock Protein family (HSPB1-HSPB10) that is ubiquitously expressed. Unlike HSPB1, HSPB4 and HSPB5, which mainly form homo- and hetero-oligomers of variable size by associating with themselves or with other HSPBs, HSPB8 forms a stable and stoichiometric complex with HSPA8/HSPA1A and its co-chaperone BAG3. Binding to BAG3 regulates HSPB8 stability, function and subcellular localization. Here, I will summarize key findings that demonstrate the role of the HSPB8-BAG3-HSPA1A chaperone complex in buffering misfolded proteins, including defective ribosomal products, and targeting them to the macroautophagy machinery for clearance. The concerted action of these three partners allows to efficiently bind to and hold misfolded species (HSPB8) and to transfer them to the autophagic vacuoles (HSPA1A and BAG3), via subsequent association with the autophagic receptor p62/SQSTM1 and the motor protein dynein. I will discuss the implication of the HSPB8-BAG3-HSPA1A chaperone complex in the maintenance of protein homeostasis under pathological conditions characterized by the accumulation of aggregation-prone proteins. I will report the identification of a novel role of the HSPB8-BAG3-HSPA1A chaperone complex in the maintenance of stress granule composition and dynamics and I will discuss how its deregulation may contribute to neurodegenerative disease progression. Finally, I will discuss how deregulation of the HSPB8-BAG3-HSPA1A complex, due to mutations in HSPB8, causes motor neuropathy and muscle atrophy

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.

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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Abstract
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

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"
Contact Name
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.