You are here: Home / Research / Upcoming Seminars

Upcoming Seminars

Antonio Rossi, Ph.D. - "In vivo models of chondrodysplasias caused by defects in proteoglycan biosynthesis: phenotyping and pharmacological approaches"

Department of Molecular Medicine Unit of Biochemistry, University of Pavia, Italy
When Nov 21, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
Add event to calendar vCal
iCal

Short CV

Abstarct
Heritable skeletal disorders are connective tissue diseases that primarily affect the development and homeostasis of the skeleton; unfortunately, in general no resolutive treatments are available for these painful conditions. Thus, the goal in this research area is the deep phenotyping of relevant in vivo and in vitro models in order to identify and test novel targets for innovative therapies.
In this respect among the skeletal disorders that are being studied in our group, Diastrophic Dysplasia (DTD) and Desbuquois Dysplasia (DBQD) are paradigmatic. Both dysplasias, with similar clinical features, are caused by defects in the biosynthesis of glycosaminoglycan (GAG) chains of proteoglycans (PGs).
DBQD type 1 is caused by mutations in the Calcium-Activated Nucleotidase 1 (CANT1) a Golgi/ER resident enzyme. To define the role of CANT1 in the etiology of DBQD, we generated Cant1 knock-in and knock-out mice. Morphological and clinical observations in the murine strains confirmed the skeletal defects described in the patients. PG synthesis was studied in rib knock-out chondrocytes; mutant cells showed GAG chains with reduced hydrodynamic size, GAG oversulfation, reduced PG synthesis and impaired secretion. This latter observation was confirmed by transmission electron microscopy of mutant vs. wild type cartilage showing the presence of dilated vacuoli suggesting a role of CANT1 in protein secretion.
Nowadays animal models are useful tools to elucidate the molecular mechanisms underlying genetic diseases as described above, but also to develop therapeutic strategies. The dtd mouse is a murine model of Diastrophic Dysplasia (DTD) a skeletal dysplasia caused by mutations in the sulfate-chloride antiporter (SLC26A2), crucial for sulfate uptake and GAG sulfation. Deep phenotyping of the model suggested that N-acetyl-L-cysteine (NAC) might play a role as an intracellular sulfate source for macromolecular sulfation. Because of the important prenatal phase of skeletal development and growth, we administered NAC in the drinking water to pregnant mice to explore a possible transplacental effect on the foetuses. A marked increase of proteoglycan sulfation was observed in dtd newborns from NAC treated pregnancies compared to the placebo group paralleled by a partial rescue of the abnormal bone morphology.
In conclusion, these different mouse models have recapitulated key aspects of disease pathology and identified new fundamental mechanisms paving the way for developing potential therapeutic approaches.

Maurizio Molinari, PhD - "Endoplasmic Reticulum-to-Lysosome-Associated Degradation of Proteasome-Resistant Protein Polymers"

Istituto di Ricerca in Biomedicina, Bellinzona, Svizzera
When Nov 28, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
Add event to calendar vCal
iCal

Short CV

Abstract
Efficient degradation of by-products of protein synthesis is required to maintain cellular proteostasis, i.e., the capacity to produce the proteome in appropriate quality and quantity. For misfolded proteins generated in the endoplasmic reticulum (ER), this mainly occurs via ER-associated degradation (ERAD), which requires dislocation across the ER membrane and degradation by cytosolic proteasomes. The mode of degradation from the ER of proteasome-resistant misfolded proteins, for example α1-antitrypsin Z (ATZ) polymers, is unknown. Here we report that luminal accumulation of polymeric ATZ activates ER-to-lysosomes-associated degradation (ERLAD). This course does not require autophagosome biogenesis, nor the intervention of ER-phagy pathways. Rather, it relies on vesicular delivery of luminal ER content to LAMP1-positive degradative organelles for clearance.

Alessandra Agresti, Ph.D. - "Inside out: the double life of nucleosomes"

In vivo Chromatin and transcription Group, Division of Genetics and Cell biology, San Raffaele Scientific Institute, Milan, Italy
When Dec 05, 2017
from 12:00 PM to 01:15 PM
Where Tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
Add event to calendar vCal
iCal

Short CV

Abstract
Contrary to what written in textbook, the amount of histones – and therefore of nucleosomes – is not a fixed parameter but a tunable one that cells exploit to adapt or respond to the external environment. We now hypothesize that histones leave the nucleus and double up as signaling factors.
Nucleosome reduction is detectable in macrophages exposed to stress signals where it facilitates the transcriptional response of inflammatory genes. Along the same line, cells progressing toward senescence reduce their nucleosome content and a similar decrease is found in cells that are genetically ablated for HMGB1 (High Mobility Group Box 1 protein).
On the contrary, the chromatin of ES cells acquires nucleosomes as differentiation progresses, suggesting that the difference in histone content can be considered as a new hallmark of pluripotency, in addition to and besides histone modifications.
Finally, histones are found in the serum of sepsis patients and their high concentration exacerbate systemic inflammation.
Many questions arise: are histones just passively released by dying cells? Or, are they also actively secreted by inflammatory cells?
Our results indicate that activated macrophages reduce their nucleosome content and concomitantly release microvesicles/exosomes (MV/E) loaded with histones. Are the two events functionally correlated? Do they represent a specialized form of intercellular communication, including to, from and between immune cells? We are trying to provide answers to these questions. 

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
Add event to calendar vCal
iCal

Short CV

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
Add event to calendar vCal
iCal

Short CV

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
Add event to calendar vCal
iCal

Short CV

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.