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Intracellular lipid droplets: using computer simulations to link biophysics with cell biology

Applicant Vanni Stefano
Number 163966
Funding scheme SNSF Professorships
Research institution Département de Biologie Faculté des Sciences Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Biophysics
Start/End 01.01.2017 - 31.12.2020
Approved amount 1'607'200.00
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All Disciplines (3)

Discipline
Biophysics
Physical Chemistry
Biochemistry

Keywords (9)

endoplasmic reticulum; hairpin topology; molecular dynamics; coarse grain simulations; lipid droplets; computational modeling; surface tension; all-atom simulations; integral membrane proteins

Lay Summary (Italian)

Lead
Le gocce lipidiche sono il principale meccanismo attraverso il quale le cellule accumulano grassi per poter affrontare eventuali periodi di scarso apporto energetico.Al momento, però, a causa di notevoli difficoltà pratiche nelle tecniche sperimentali usate per studiarle, le proprietà' strutturali e biofisiche di queste strutture cellulari sono in larga parte oscure.Questo progetto intende sviluppare nuove tecniche computazionali per studiare le gocce lipidiche a livello molecolare e comprendere nel dettaglio i meccanismi cellulari in cui queste sono coinvolte.
Lay summary
Nel corpo umano, il grasso viene accumulato in compartimenti intracellulari altamente specializzati: le gocce lipidiche. Fino a pochi anni fa, queste gocce erano considerate serbatoi di energia pressoché inerti, ma studi recenti hanno indicato come queste strutture siano altamente dinamiche e giochino un ruolo centrale in numerosi processi cellulari, tra cui la proteolisi o la replicazione virale. Questi processi sono cruciali in molte condizioni, sia fisiologiche che patologiche, tra cui l'obesità e le malattie metaboliche.

L'obiettivo di questo progetto è di far luce sulle proprietà microscopiche delle gocce lipidiche e di chiarire il loro ruolo nella regolazione di differenti processi cellulari. A questo scopo, svilupperò nuovi e più accurati modelli computazionali per descrivere le gocce lipidiche, e studierò in dettaglio sia le loro proprietà chimiche sia la loro interazione con varie proteine.

Lo scopo finale é quello di ottenere una descrizione ad alta risoluzione di queste strutture cellulari, al fine di proporre un modello interpretativo coerente con i dati sperimentali attualmente disponibili e per progettare nuovi approcci sperimentali in vivo e in vitro per fare luce sulle basi molecolari della biologia delle gocce lipidiche e sui meccanismi patologici che le coinvolgono.
Direct link to Lay Summary Last update: 31.10.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets
ValeriaZoni, RashaKhaddaj, PabloCampomanes, Abdou RachidThiam, RogerSchneiter, StefanoVanni (2021), Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets, in Elife, 10, e62886.
Ceramide chain length–dependent protein sorting into selective endoplasmic reticulum exit sites
SofiaRodriguez-Gallardo, KazuoKurokawa, SusanaSabido-Bozo, AlejandroCortes-Gomez, AtsukoIkeda, ValeriaZoni, AuxiliadoraAguilera-Romero, Ana MariaPerez-Linero, SergioLopez, MihoWaga, MisakoAraki, MiyakoNakano, HowardRiezman, KouichiFunato, StefanoVanni, AkihikoNakano, ManuelMuniz (2020), Ceramide chain length–dependent protein sorting into selective endoplasmic reticulum exit sites, in Science Advances, 6(50), eaba8237.
Conserved functions of ether lipids and sphingolipids in the early secretory pathway
Noemi Jimemez-Rojo, Manuel Leonetti, Valeria Zoni, Adai Colom, Suihan Feng, Namrata Iyengar, Stefano Matile, Aurelien Roux, Stefano Vanni, Jonathan Weissman, Howard Riezman (2020), Conserved functions of ether lipids and sphingolipids in the early secretory pathway, in Current Biology, 30(19), 3775-3787.
Accurate Estimation of Membrane Capacitance from Atomistic Molecular Dynamics Simulations of Zwitterionic Lipid Bilayers
Vikram ReddyArdham, ValeriaZoni, SylvainAdamowicz, PabloCampomanes, StefanoVanni (2020), Accurate Estimation of Membrane Capacitance from Atomistic Molecular Dynamics Simulations of Zwitterionic Lipid Bilayers, in Journal of Physical Chemistry B, 124(38), 8278-8286.
How Do Ethanolamine Plasmalogens Contribute to Order and Structure of Neurological Membranes?
West Ana, Zoni Valeria, Teague Walter E, Leonard Alison N., Vanni Stefano, Gawrisch Klaus, Tristram-Nagle Stephanie, Sachs Jonathan N., Klauda Jeffery B. (2020), How Do Ethanolamine Plasmalogens Contribute to Order and Structure of Neurological Membranes?, in The Journal of Physical Chemistry B, 124(5), 828-839.
Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity
Campomanes Pablo, Zoni Valeria, Vanni Stefano (2019), Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity, in Communications Chemistry, 2(1), 1.
Proteomics-Based Monitoring of Pathway Activity Reveals that Blocking Diacylglycerol Biosynthesis Rescues from Alpha-Synuclein Toxicity
SosteMartin, Charmpi Konstantina, Lampert Fabienne, GerezJuan Atilio, van OostrumMark, MalinovskaLiliana, BoersemaPaul Jonathan, PrymaczokNatalia Cecilia, RiekRoland, PeterMatthias, VanniStefano, BeyerAndreas, PicottiPaola (2019), Proteomics-Based Monitoring of Pathway Activity Reveals that Blocking Diacylglycerol Biosynthesis Rescues from Alpha-Synuclein Toxicity, in Cell Systems, 9(3), 309.
Structure and Dynamics of the Acyl Chains in the Membrane Trafficking and Enzymatic Processing of Lipids
Vanni Stefano, Riccardi Laura, Palermo Giulia, Vivo Marco De (2019), Structure and Dynamics of the Acyl Chains in the Membrane Trafficking and Enzymatic Processing of Lipids, in Accounts of Chemical Research, 52(11), 3087.
To Bud or Not to Bud: A Perspective on Molecular Simulations of Lipid Droplet Budding
ZoniValeria, NietoVincent, EndterLaura J, RisseladaHerre Jelger, MonticelliLuca, VanniStefano (2019), To Bud or Not to Bud: A Perspective on Molecular Simulations of Lipid Droplet Budding, in Frontiers in Molecular Biosciences, 6, 124.
Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology
Friedman Ran, Khalid Syma, Aponte-Santamaria Camilo, Arutyunova Elena, Becker Marlon, Boyd Kevin J., Christensen Mikkel, Coimbra Joao T. S., Concilio Simona, Daday Csaba, van Eerden Floris J., Fernandes Pedro A., Graeter Frauke, Hakobyan Davit, Heuer Andreas, Karathanou Konstantina, Keller Fabian, Lemieux M. Joanne, Marrink Siewert J., May Eric R., Mazumdar Antara, Naftalin Richard, Pickholz Monica, Piotto Stefano, Pohl Peter, Quinn Peter, Ramos Maria J., Schiott Birgit, Sengupta Durba, Sessa Lucia, Vanni Stefano, Zeppelin Talia, Zoni Valeria, Bondar Ana-Nicoleta, Domene Carmen (2018), Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology, in JOURNAL OF MEMBRANE BIOLOGY, 251(5-6), 609-631.
PackMem: A Versatile Tool to Compute and Visualize Interfacial Packing Defects in Lipid Bilayers
Gautier Romain, Bacle Amélie, Tiberti Marion L, Fuchs Patrick F, Vanni Stefano, Antonny Bruno (2018), PackMem: A Versatile Tool to Compute and Visualize Interfacial Packing Defects in Lipid Bilayers, in Biophysical journal, 115(3), 436-444.
Intracellular Lipid Droplets: From Structure to Function.
Stefano Vanni (2017), Intracellular Lipid Droplets: From Structure to Function., in Lipid Insights, 10, 1-3.
Toward Chemically Resolved Computer Simulations of Dynamics and Remodeling of Biological Membranes
Soares T. A., Vanni S., Milano G., Cascella M. (2017), Toward Chemically Resolved Computer Simulations of Dynamics and Remodeling of Biological Membranes, in Journal of Physical Chemistry Letters, 8(15), 3586-3594.
Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure
ValeriaZoni, RashaKhaddaj, IvanLukmantara, WataruShinoda, HongyuanYang, RogerSchneiter, StefanoVanni, Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure, in Proceedings of the National Academy of Sciences.

Datasets

Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets

Author Valeria, Zoni; Rasha, Khaddaj; Pablo, Campomanes; Abdou Rachid, Thiam; Roger, Schneiter; Stefano, Vanni
Publication date 22.01.2021
Persistent Identifier (PID) http://doi.org/10.5281/zenodo.4457468
Repository Zenodo


Collaboration

Group / person Country
Types of collaboration
Patricia Bassereau lab/Institut Curie Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Rachid Thiam Lab/ENS Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Roger Scheniter lab/ University of Fribourg Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Manuel Muniz lab Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Paola Picotti lab/ETHZ Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Jason Schnell lab/Oxford University Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Howard Riezman lab/UNIGE Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
The Lipid Droplets Conference Talk given at a conference A molecular view of lipid droplet biogenesis 06.07.2020 online, United States of America Vanni Stefano;
LS2 Annual Meeting Talk given at a conference Lipid droplet biogenesis as a liquid-liquid phase separation 13.02.2020 Zurich, Switzerland Vanni Stefano;
Molecular simulation symposium Poster Lipid droplet biogenesis is a liquid phase separation spatially regulated by seipin and membrane curvature 09.12.2019 Nagoya, Japan Zoni Valeria;
Modeling phase separation in health and diseases: from nano- to miso-scale Talk given at a conference Lipid droplet biogenesis is driven by a liquid-liquid phase separation 30.09.2019 Toulouse, France Vanni Stefano;
CECAM50 Poster Molecular simulations of cellular membranes: coming of age? 26.09.2019 Lausanne, Switzerland Vanni Stefano;
PhD SwissSoftDays Talk given at a conference The physical chemistry of lipid droplet biogenesis 27.08.2019 Lausanne, Switzerland Zoni Valeria;
Joint 12th EBSA, 10th ICBP-IUPAP Biophysics Congress Poster Molecular dynamics investigation of protein-membrane association 20.07.2019 Madrid, Spain Sririvasan Sriraksha;
Joint 12th EBSA, 10th ICBP-IUPAP Biophysics Congress Poster The physical chemistry of lipid droplet biogenesis 20.07.2019 Madrid, Spain Zoni Valeria;
NCCR Chemical Biology Summer Retreat Talk given at a conference Molecular biophysics of cellular membranes 13.06.2019 Villars-sur-Ollon, Switzerland Vanni Stefano;
BeFri Research Retreat 2019 Poster The physical chemistry of lipid droplet biogenesis 09.05.2019 Kandersteg, Switzerland Zoni Valeria;
Swiss Soft Days 2019 Talk given at a conference Droplet Induced Deformations on Soft surfaces 22.03.2019 Fribourg, Switzerland Ardham Vikram Reddy;
Biophysical Society Meeting Poster Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity 02.03.2019 Baltimore, United States of America Campomanes Pablo; Vanni Stefano;
Leman lipid club Talk given at a conference Molecular biophysics of cellular membranes 20.02.2019 Lausanne, Switzerland Vanni Stefano;
Multiscale Modeling from Macromolecules to Cell: Opportunities and Challenges of Biomolecular Simulations, Talk given at a conference The physical chemistry of lipid droplet biogenesis 04.02.2019 Lausanne, Switzerland Vanni Stefano;
Multiscale Modeling from Macromolecules to Cell: Opportunities and Challenges of Biomolecular Simulations Poster Unveiling the role of ether lipids in Golgi-ER retrograde transport 04.02.2019 Lausanne, Switzerland Zoni Valeria;
The 2018 Golgi Meeting ‘Membrane trafficking in cell organization and homeostasis Poster The physical chemistry of lipid droplet biogenesis 15.10.2018 Sorrento, Italy Vanni Stefano;
Liquid Liquid Phase Separation in Cells Talk given at a conference Towards a molecular view of lipid droplet biology 23.05.2018 Lausanne, Switzerland Vanni Stefano;
EMBO | EMBL Symposium: Cellular Mechanisms Driven by Liquid Phase Separation Poster Towards a molecular view of lipid droplet biogenesis 13.05.2018 Heidelberg, Germany Vanni Stefano;
Frontiers in Computational Biophysics: understanding conformational dynamics of complex lipid mixtures relevant to biology Talk given at a conference Towards a molecular view of lipid droplet biology 10.01.2018 Lugano, Switzerland Zoni Valeria; Vanni Stefano;
Soft matter interfaces: from biology to engineering applications Talk given at a conference Which oil is right for you? An atomistic view of oil-lipid-water interfaces. 05.11.2017 Ascona, Switzerland Vanni Stefano;
Molecular and Cell Biology of Membranes Poster Towards a molecular view of lipid droplet biology 21.05.2017 EMBL Heidelberg, Germany Vanni Stefano;
Molecular basis for membrane remodelling and organization Talk given at a conference Towards a molecular view of lipid droplet biology 03.04.2017 Roscoff, France Vanni Stefano;
Structured Soft Interfaces: Caught Between Multi-Scale Simulation and Application Talk given at a conference Making sense of membrane diversity in vesicular trafficking pathways, atom by atom. 23.01.2017 Leiden, Netherlands Vanni Stefano;


Self-organised

Title Date Place
Swiss Soft Days 22.03.2019 Fribourg, Switzerland

Communication with the public

Communication Title Media Place Year

Awards

Title Year
ETHZ/JSPS fellowship - exchange fellowship for young researchers between Switzerland and Japan 2019

Associated projects

Number Title Start Funding scheme
194807 Intracellular lipid droplets: using computer simulations to link biophysics with cell biology 01.01.2021 SNSF Professorships

Abstract

Cellular membranes play a huge role in a myriad of key cellular processes as diverse and fascinating as vesicle trafficking, receptor functioning or synaptic transmission. Yet, due to intrinsic limitations of biophysical and biochemical methods when dealing with a membrane-mimetic environment, a high-resolution knowledge of the basic physicochemical principles that govern these processes is still limited. In this context, in silico modeling is a promising alternative strategy, since computational-based studies offer the possibility to investigate the behavior of matter directly at the atomistic level under highly controlled conditions. In this project, I plan to improve the current capabilities of computational models to describe complex biological-like membranes, with a special focus on the role of surface tension on membrane interfacial properties. These developments will be used to characterize in silico the unique membrane of lipid droplets (LDs), a remarkably fascinating organelle that consists of a hydrophobic core of neutral lipids surrounded by a phospholipid monolayer, and to investigate how its physicochemical properties modulate the interactions between LDs and a unique family of integral membrane proteins that is enriched in LDs: those that possess a hairpin-like topology in their membrane-bound domain. The high-resolution picture that will emerge from the simulations will provide a new conceptual framework to interpret biophysical and cellular experiments on LDs, and it will lead to the rational design of experimental approaches to understand the molecular basis of LD biology and of related diseases.
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