Emplois
>
Paris

    PhD thesis project - Paris, France - Institut Curie

    Institut Curie
    Institut Curie Paris, France

    il y a 4 jours

    Default job background
    Description
    Institut Curie is a key player in the fight against cancer, combining an internationally renowned Research center with a state-of-the-art Hospital complex. Founded in 1909 by Marie Curie, Institut Curie brings together more than 3 700 researchers, doctors and caregivers at three sites (Paris, Saint-Cloud and Orsay) to carry out three missions: research, care, and the preservation and transmission of knowledge. Institut Curie is a private foundation recognized as a public interest institution. The Curie model, with its continuum from research to care, is now being applied in its modern form through its Curie 2030 strategic project.

    Description of the PhD thesis project

    Abstract

    Fundamental cell physiology originates from conformational changes and diffusion dynamics of membrane proteins embedded in the lipid bilayer. However, studying the interplay between nanoscale protein conformations and membrane mechanics is inherently challenging in cell-based experiments. In addition, the effect of membrane properties on the conformational cycles, and thus in the protein's activity remains an open question. In this thesis, we aim to investigate the diffusion dynamics and conformational heterogeneity of multidrug resistance ABC transporter BmrA as a function of its conformation, post-hydrolytic (closed) and apo (open). Diffusion analysis might reveal the formation of protein clusters in the different conditions. To this end, the PhD student will perform single-particle tracking measurements and single-molecule FRET experiments on BmrA reconstituted in giant unilamellar vesicles (GUVs) with controlled and varying membrane tensions. Combining advanced optical methods with biochemical approaches, this project will bring fundamental insights into the intrinsic diffusion dynamics of an active membrane transporter and its clustering in relation to membrane mechanics and conformational cycles; all possibly influencing the cell function.

    Background

    Our team has pioneered studies on membrane protein dynamics using micropipette-aspirated GUV systems combined with single-molecule tracking. More recently, during her PhD, A. Damm obtained evidence of membrane curvature-induced enhanced opening of protein conformations and thus perturbing its activity. The new PhD student will benefit from these established biochemical assays and custom built single-molecule microscopes, to tackle open questions in membrane biophysics to systematically decouple the role of intrinsic protein dynamics from protein-protein interactions and membrane-mediated effects.

    Objectives

    1. Effect of membrane tension on BmrA catalytic cycle (and thus its activity): We will employ GUV assay at very low protein density to probe the effect of membrane stretching on the dynamics of conformational changes of single transporter. Using single-molecule FRET coupled to single molecule tracking, we will measure the ATP dependence of the opening and closing rates for varying tensions relevant for physiological conditions. These results will be compared to a theoretical model developed by Pierre Sens's group.

    2. Effect of protein conformational dynamics on its diffusion in membranes: Our team have discovered that proteins with similar sizes, but different shapes can have different motilities when the membrane tension is lowered. However, the mobility of a protein that constantly switches conformation is not known. To this end, we aim to measure the effect of protein activity on the mobility of single BmrA in membranes using single-particle tracking. Moreover, we expect that membrane deformations induced by the conformational switches might generate active protein clusters in the membrane, revealed by the protein mobility.

    Experimental approaches

    The PhD candidate will benefit from training in experimental biophysics. In particular, concepts and tools regarding the use of biomimetic systems combined with state-of-the-art single-molecule fluorescence spectroscopies will be employed to study spatial-temporal dynamics of membrane proteins (also see Figure below). The candidate will also work in close collaborations with theoreticians to provide physical models/frameworks of protein fluctuating/clustering while undergoing conformational switches in membranes.

    International, interdisciplinary & intersectoral aspects of the project

    The PhD candidate will benefit from the existing network, both national and international teams including computational microscopy and machine learning approaches for single-molecule data analysis. This project will be developed in close collaboration with Daniel Lévy (membrane protein expert) within the department and with the theoreticians of the lab.

    We employ biochemistry (for in-vitro protein reconstitution), synthetic biology (such as click-chemistry for site-specific fluorescence labeling), and advanced optical methods (single-molecule FRET, single particle tracking, fluorescence correlation spectroscopy) to explore the influence of conformations and protein diffusion in bio membranes. Thus, the PhD candidate will benefit from a highly interdisciplinary and multinational research environment located in the historic neighborhood of Paris.

    Recent publications

    1. Damm A. Interplay between the conformational dynamics of a transmembrane protein and the mechanical properties of its surrounding membrane (Doctoral dissertation, Sorbonne Université, 2019), updated results arriving soon in bioRxiv.

    2. Srinivasan S, Regmi R, Lin X, Dreyer CA, Chen X, Quinn SD, He W, Coleman MA, Carraway III KL, Zhang B, Schlau-Cohen GS. Ligand-induced transmembrane conformational coupling in monomeric EGFR. Nature Communications. 2022;13(1):3709.

    3. Regmi R, Srinivasan S, Latham AP, Kukshal V, Cui W, Zhang B, Bose R, Schlau-Cohen GS. Phosphorylation-dependent conformations of the disordered carboxyl-terminus domain in the epidermal growth factor receptor. The journal of physical chemistry letters. 2020;11(23):

    4. Quemeneur F, Sigurdsson JK, Renner M, Atzberger PJ, Bassereau P, Lacoste D. Shape matters in protein mobility within membranes. Proceedings of the National Academy of Sciences. 2014;111(14):5083-7.

    5. Tsai FC, Simunovic M, Sorre B, Bertin A, Manzi J, Callan-Jones A, Bassereau P. Comparing physical mechanisms for membrane curvature-driven sorting of BAR-domain proteins. Soft Matter. 2021;17(16):

    Interdisciplinary profile with exposure to either of the following research domains:


    • Biochemistry of membrane proteins, and model membrane systems


    • Fluorescence microscopy and/or advanced optical techniques such as single particle tracking and single molecule FRET experiments

    Expected courses/training include topics on soft matter, biophysics, optics, etc.

    Fluent in English

  • Université Paris-Saclay GSLife Sciences and Health

    Régulations de L'épissage Des Arn Par de Nouveaux

    il y a 1 semaine

    Université Paris-Saclay GSLife Sciences and Health Paris, France

    **Régulations de l'épissage des ARN par de nouveaux partenaires du facteur U2AF. // RNA splicing regulations by novel U2AF partners.**: · - Réf **ABG-120245** · **ADUM-52933** · - Sujet de Thèse- 13/02/2024- Université Paris-Saclay GSLife Sciences and Health- Lieu de travail- Evr ...

  • Université Paris-Saclay GS Informatique et sciences du numérique

    Synthèse D'animation 3D à Partir Des Instructions

    il y a 1 semaine

    Université Paris-Saclay GS Informatique et sciences du numérique Paris, France

    **Synthèse d'animation 3D à partir des instructions textuelles // AI-Generated 3D Animations with Text Prompts**: · - Réf · - **ABG-118377** · **ADUM-51674** · - Sujet de Thèse- 23/11/2023- Université Paris-Saclay GS Informatique et sciences du numérique- Lieu de travail- Evry Ce ...

  • Caisse de dépôt et placement du Québec

    Associate, Infrastructure

    il y a 2 jours

    Caisse de dépôt et placement du Québec Paris, France

    Job Description · Role · The Analyst will support CDPQ's ongoing efforts toward its business objectives by advising on transaction execution based on the required risk and return and by helping with post-investment management of CDPQ's assets in Europe. The Analyst will also assi ...

  • SCOR

    Investor Relations Intern

    il y a 1 semaine

    SCOR Paris, France

    The Investor Relations department is key in interfacing directly with investors (e.g. current and potential shareholders and the broader financial community) as well as sell-side analysts /brokers. Additionally, the department assists the financial community in understanding SCOR ...

  • SCOR

    Strategic Analysis Intern

    il y a 1 semaine

    SCOR Paris, France

    The Investor Relations department is key in interfacing directly with investors (e.g. current and potential shareholders and the broader financial community) as well as sell-side analysts/brokers / rating agencies. The department assists the financial community in understanding S ...

  • Pernod Ricard

    Consumer Understanding and Targeting Senior Planner

    il y a 1 semaine

    Pernod Ricard Paris, France

    Want to join a fast-moving and responsible company, and work among convivial teams? Pernod Ricard is looking for a Consumer Understanding and Targeting Senior Planner to drive strategy and growth You will be based at The Island, our office in central Paris. · Who are we: · Pernod ...

  • Partech Partners

    Partech Growth

    il y a 2 jours

    Partech Partners Paris e, France

    We are opening a Paris-based position for a 6-month **internship in our Growth equity investment team**, starting in January 2023. · You will be joining a team of 11 people focusing on Partech's Growth equity strategy, based at the Partech Shaker - our building in the 2nd arrondi ...

  • Université Paris-Saclay GSLife Sciences and Health

    Développement Et évaluation Clinique D'une

    il y a 1 semaine

    Université Paris-Saclay GSLife Sciences and Health Villejuif, France

    **Développement et évaluation clinique d'une virothérapie anti-tumorale innovante // Development and clinical evaluation of an innovative anti-tumor virotherapy**: · - Réf · - **ABG-111123** · **ADUM-46354** · - Sujet de Thèse- 14/02/2023- Cifre- Université Paris-Saclay GSLife Sc ...

  • Institut Supérieur d'Electronique de Paris (ISEP)

    Stage de Fin D'étude: Anomaly Detection in Iot

    il y a 6 jours

    Institut Supérieur d'Electronique de Paris (ISEP) Issy-les-Moulineaux, France

    _**Internship: State of the art solutions for Anomaly Detection in IoT Environments**_ · **General presentation / Technological context** · The world is moving fast toward an era of Web 3.0. The Internet of Things (IoT), part of such an evolution, connects smart devices to digita ...

  • Observatoire de Paris

    Dynamique Et Nature Des Galaxies Naines

    il y a 6 jours

    Observatoire de Paris Meudon, France

    **Dynamique et nature des galaxies naines irrégulières // Nature and dynamics of dwarf irregular galaxies**: · - Réf · - **ABG-110398** · **ADUM-45722** · - Sujet de Thèse- 21/01/2023- Observatoire de Paris- Lieu de travail- Meudon - France- Intitulé du sujet- Dynamique et nature ...

  • HITACHI ASTEMO FRANCE S.A.S.

    Phd Candidate

    il y a 1 semaine

    HITACHI ASTEMO FRANCE S.A.S. Drancy, France

    **Description** · **Ready to contribute to the future of the automotive industry?** · We are Hitachi Astemo France S.A.S, part of Hitachi Astemo, focusing on world-leading advanced mobility solutions within the fields of electrification, autonomous driving, and connectivity to he ...

  • HITACHI ASTEMO FRANCE S.A.S.

    Phd Candidate

    il y a 1 semaine

    HITACHI ASTEMO FRANCE S.A.S. Drancy, France

    **Description** · **Ready to contribute to the future of the automotive industry?** · We are Hitachi Astemo France S.A.S, part of Hitachi Astemo, focusing on world-leading advanced mobility solutions within the fields of electrification, autonomous driving, and connectivity to he ...

  • INRIA

    Securing Algorithms for Classification and

    il y a 1 semaine

    INRIA Versailles, France

    **PhD Position F/M**: · **Securing Algorithms for Classification and Machine Learning on Personal Data using Trusted Execution Environments** · **Supervision **:Iulian Sandu Popa (Iulian.Sandu-Popa at ), Nicolas Anciaux (Nicolas.Anciaux at ) · **Context.** · **Objectives of the t ...

  • Université Paris-Saclay GS Sport, Mouvement, Facteurs Humains

    Thèse en Management Du Sport ou économie Du Sport

    il y a 1 semaine

    Université Paris-Saclay GS Sport, Mouvement, Facteurs Humains Orsay, France

    **Thèse en management du sport ou économie du sport // PhD project in sport management or sport economics**: · - Réf · - **ABG-111080** · **ADUM-46107** · - Sujet de Thèse- 12/02/2023- Université Paris-Saclay GS Sport, Mouvement, Facteurs Humains- Lieu de travail- Orsay cedex - F ...

  • École polytechnique

    Satellites Plasmoniques Photo-induits

    il y a 1 semaine

    École polytechnique Palaiseau, France

    **Satellites plasmoniques photo-induits // Photinduced plasmonic satellites**: · - Réf · - **ABG-111189** · **ADUM-46432** · - Sujet de Thèse- 16/02/2023- École polytechnique- Lieu de travail- Palaiseau - France- Intitulé du sujet- Satellites plasmoniques photo-induits // Photind ...

  • L'École polytechnique

    Bachelor Program Academic Officer

    il y a 4 jours

    L'École polytechnique Palaiseau, France

    **École polytechnique** (also known as "L'**X**") is a world-class higher education and research establishment dedicated to sciences and technology, **founded in 1794**. The School granted a **military status** in 1804, and operates under the administrative supervision of the Min ...

  • Université Paris-Saclay GS Biosphera - Biologie, Société, Ecologie & Environnement, Ressources, Agri

    Comment Les Endophytes Impactent La Nodulation Chez

    il y a 6 jours

    Université Paris-Saclay GS Biosphera - Biologie, Société, Ecologie & Environnement, Ressources, Agri Orsay, France

    **Comment les endophytes impactent la nodulation chez les plantes légumineuses // How endophytes impact symbiotic nodulation in legume plants**: · - Réf **ABG-121320** · **ADUM-55011** · - Sujet de Thèse- 16/03/2024- Université Paris-Saclay GS Biosphera - Biologie, Société, Ecolo ...

  • Groupe Français de Rhéologie

    Thèse - PhD Thesis in partnership with Stellantis - Industrial dip-coating process study using

    il y a 1 semaine

    Groupe Français de Rhéologie Paris, France

    Thèse - PhD Thesis in partnership with Stellantis - Industrial dip-coating process study using complex shapes and non-Newtonian fluids · Description: · Full description: · Context: · Dip-coating processes consist in covering an object with a thin layer of liquid, using sequen ...

  • Centeon

    Research Associate

    il y a 2 jours

    Centeon Paris, France

    Company Mission: · Centeon (stealth mode) is a low-carbon chemicals company. Our vision is to develop and to scale a breakthrough pathway for the low-energy, low-carbon production of commodity chemicals in service of today's energy transition. · Job Mission: · We are looking for ...

  • INRIA

    PhD Position F/M Campagne doctorant 2024

    il y a 6 jours

    INRIA Paris, France CDD

    Contexte et atouts du poste · The PhD thesis witll be co-supervised by Mario Sigalotti (CAGE) and Eugenio Pozzoli (CNRS, IRMAR). · Mission confiée · The goal of this project consists in developing nonlinear geometric control methods for the analysis of bilinear partial differe ...