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Upcoming Seminars

Giuseppe Testa, MD., Ph.D - "Disease avatars: cell reprogramming and the functional annotation of human genomes"

Professor of Molecular Biology, Department of Oncology and Hemato-Oncology, University of Milan, Director of Laboratory of Stem Cell Epigenetics, European Institute of Oncology, Milan, Italy
When Feb 21, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Curriculum Vitae

Astract

The in vitro recapitulation of human development, largely propelled by cell reprogramming, is transforming medicine by making genetic variation and disease predisposition experimentally tractable. This is especially true for disorders of the nervous system, for which cell reprogramming is particularly relevant due to the inaccessibility of relevant tissues, and whose main disease-associated genes are strongly enriched for transcription factors and chromatin regulators. Chromatin function has emerged as a central domain of dysregulation in the pathogenesis of intellectual disability (ID) and autism spectrum disorder (ASD), with a steadily increasing number of genes encoding for key chromatin modulators causally associated to these conditions. Transcriptional and chromatin dysregulation is thus a privileged entry point into the mechanistic underpinnings of neurodevelopmental conditions, yielding relatively rapid molecular insight for bridging genetic or environmental lesions to in vivo phenotypes. In our lab we focus on a selected group of ID and/or ASD conditions caused by point mutations or dosage imbalances affecting chromatin pathways with a critical function in neural development. I will discuss a summary of our latest inroads into these disorders, including novel insights from an integrated platform of 2D and 3D stem cell-based models of neural development through which we investigate convergent chromatin dysfunction brought about by genetic and environmental causes of intellectual disability.

Roberto Sitia, M.D. - "Editing the Secretome: Signal Integration at the ER-Golgi Interface"

Head of Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, Ospedale San Raffaele IRCCS, Milan, Italy
When Feb 28, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium Vesuvius
Contact Name
Contact Phone 081-19230659
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Abstract
Cells communicate with the external world by releasing and expressing proteins on their surfaces. Fidelity is essential, but also is efficiency, particularly for professional secretors such as  pancreatic or plasma cells.  This 40 min talk will describe how cells manage to operate their protein factory presto e bene, focussing on particularly demanding molecules of biomedical relevance, like polymeric antibodies and metalloproteases. Unexpected links between proteostasis in the early secretory compartments and signalling reveal how cells continuously adjust essential parameters such as nutrient supply, factory (re)organization and export control. 

Scott David Emr, Ph.D. - "Sorting out membrane traffic to the lysosome: Ubiquitin, ESCRTs and protein quality control Systems”

Professor of Molecular Biol. and Genetics; Director, Weill Institute for Cell and Mol. Biol., Cornell University, Ithaca (NY), USA
When Mar 02, 2017
from 11:00 AM to 12:15 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Curriculum Viate

Abstract
The Emr lab has focused its efforts on the molecular mechanisms responsible for the biogenesis, maintenance and function of the lysosome. We have used the single-cell yeast Saccharomyces cerevisiae as a genetic model system to discover and isolate the complex machinery that sort and deliver proteins and enzymes to lysosomes. One set of proteins, the ESCRT complexes (ESCRT-0, -I, -II, -III, and the Vps4 ATPase), sort cell surface receptors and membrane proteins into vesicles that invaginate and bud into the lumen of the late endosome (forming multi-vesicular bodies, MVBs). These MVBs then fuse with the lysosome delivering the vesicles containing the membrane proteins into the lumen of the lysosome where they are degraded. Recent biochemical and structural studies in our lab have identified the ESCRT-III complex as a vesicle budding machine. The ESCRTs mediate not only MVB formation but also, other important cellular processes, including the budding enveloped viruses like HIV, cytokinesis, plasma membrane repair, and nuclear envelope reformation. Recently, our lab also uncovered a pathway for the selective sorting and degradation of lysosomal membrane proteins. This selective degradation process requires activation of a novel lysosome-anchored ubiquitin ligase complex. Lysosomal membrane proteins are sorted and degraded in the lumen of the lysosome in an ESCRT-dependent process.

Tomas Kirchhausen, M.S., Ph.D. - "Cellular Dynamics imaged in real time and in 3D: the mechanism"

Professor of Cell Biology and Professor of Pediatrics, Harvard Medical School, Boston Children’s Hospital, Boston (MA) - USA
When Mar 02, 2017
from 12:20 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Curriculum Vitae

Abstract
Four years ago it would have been unheard off. Three years ago, it was a dream. Now, it’s a reality. By using ultra-thin sheets of light to rapidly illuminate biological samples with extremely low photon doses, 3D experiments previously limited to seconds or minutes by photo-bleaching or by photo-toxicity, can now be extended to hours or days. The lattice light sheet microscope invented by Eric Betzig is a new fluorescence visualization tool that can image living cells in action, from single molecules to organelle biogenesis to cell migration, with unprecedented duration at diffraction limited resolution and high-temporal resolution. The talk will illustrate our most recent efforts mainly using the lattice light sheet microscope to ‘see’ in three dimensions processes that mediate and regulate the movement of vesicular carriers throughout cells and the biogenesis of organelles in both, isolated cells maintained in tissue culture conditions and cells within tissues of a living zebrafish embryo. It will also illustrate our analysis of the recruitment dynamics of ESCRT-III and Vps4 revealed the mechanism of reverse membrane budding and fission on endosomes. The data is consistent with a model whereby that Vps4 acts as a ATP-dependent molecular ratchet to stochastically mediate the clustering of relatively short curved ESCRT-III filaments; at early stages, the uncoordinated ATP-dependent ratchet activity of several Vps4 hexamers promotes membrane bulging, i.e. ILV budding; at later stages, the rachet activity facilitates the apposition of the opposing membrane leaflets of the bulged cone leading to membrane fusion, release of the ILV and creation of MVBs.

Shawn M. Ferguson, Ph.D. - "Lysosome Function, Dysfunction and Neurodegenerative Disease"

Associate Professor, Department of Cell Biology, Yale University, New Haven, CT - USA
When Mar 03, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Curriculum Vitae

Abstract

The goal of research in my lab is to understand how the status of lysosomes is sensed and how lysosomal function is regulated to meet cellular demands.  We focus in particular on the interface between the cell biological mechanisms that regulate lysosome homeostasis and the contributions of dysfunctional lysosomes to neurodegenerative disease. We are in particular interested in Alzheimer’s disease and the amyotrophic lateral sclerosis-frontotemporal dementia spectrum due to the convergence of clues from human genetics and brain pathology that has indicated major roles for lysosome dysfunction in these diseases. We address these questions in mouse models, human induced pluripotent stem cells and mammalian cell lines.