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kfield 17/12/2014 GIANT International Internship programme: Summer 2015 research projects

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kfield

17/12/2014GIANT International Internship programme: Summer 2015 research projects

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Research projects for international students –GIANT International Internship Programme 2015

The GIANT International Internship Program (GIIP) is a ten-week research internship programme scheduled to take place from May 25th to July 31st, 2015. Some partner laboratories may be able to extend the duration of the program.

Research project 1: Understanding the role of SEPALLATA3 splice variants in flower development......................................................................................................................... 2

Research project 2: From gene to potassium channel blockers............................................3

Research project 3: Designing novel anti-inflammatory drugs by targeting the CD domain of the MAP kinase p38α........................................................................................................4

Research project 4: Commissioning of, and first experiments on, the new instrument for in situ studies of nanoparticles and nanowires during their elaboration, using synchrotron X rays at the ESRF.....................................................................................................................5

Research project 5: Probing the flexibility in the complement proenzyme C1r2C1s2 of innate immunity by cryo-electron microscopy..................................................................................6

Research project 6: Self-assembling protein-based bionanowires........................................7

Research project 7: Energy Efficient Integrated Circuits for Brain Computer Interface systems................................................................................................................................. 8

Research project 8: Theoretical prediction of stable B and N-doped C60 and their synthesis pathways...............................................................................................................................9

Research project 9: Capillary microfluidics: achieving valving of spontaneous capillary flows by electro-capillary means.........................................................................................10

Research project 10: Optical spectrometer for trace detection of NO in breath analysis....11

Research project 11: Novel tools for the identification of small molecule –protein interactions......................................................................................................................... 12

Research project 12: Influence of neighbouring dielectric on the performance of UHF RFID Tags – survey and enhancement.........................................................................................12

Research project 13: Theory of spin-photon interfaces. Foundations and potential for quantum technologies.........................................................................................................13

Research project 14: Microfluidic system for continuous cell culture..................................14

Research project 15: Characterization of the biochemical and biological functions of a chromatic factor..................................................................................................................15

Research project 16: Fabrication of biocatalytic electrodes for bioenergy conversion using carbon nanostructures........................................................................................................16

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Research project 17: Intrinsically disordered Proteins: how do they work ?......................17

Research project 1: Understanding the role of SEPALLATA3 splice variants in flower development

Supervisor’s name: Chloe Zubieta

Lab: LPCV

Administrative contact: Sophie Mistri ; [email protected]

Key words to describe the project:

Transcription factors, SEPALLATA3, flower development, floral organs, ChIP-seq, MADS

Description of the project:

Floral organ development is orchestrated by the MADS family of transcription factors. These transcription factors are present in all eukaryotes, but in higher plants the family has undergone a large expansion. For examples, mammals have about 5 MADS transcription factors whereas Arabidopsis has over 100. In addition, angiosperms have added plant-specific domains to the MADS transcription factors which allow the proteins to form oligomeric complexes. Current hypothesis for flower development rely on the formation of these complexes to trigger different developmental programs. The MADS transcription factor, SEPALLATA3 (SEP3), is involved in the formation of all floral organs. SEP3 has three splice variants in Arabidopsis and these splice variants are able to form different protein complexes based on our crystallographic studies. The project aim is 1) to identify the target genes of the different SEP3 splice variants via chromatin immune-precipitation followed by deep sequencing (ChIP-seq) and 2) help create Arabidopsis mutants that have only one splice variant and examine the phenotype. These data will allow us to identify downstream pathways and targets of each SEP3 splice variant, understand the role of different splice variants in flower development and integrate our knowledge of the atomic structure of SEP3 with effects at the organismal level.

Skills required: A background in plant biology is recommended. Experience in chromatin immune-precipitation is also desired

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Research project 2: From gene to potassium channel blockers

Supervisor’s name: Beatrice Schaak ; [email protected]

Lab: IBS CEA

Administrative contact: Josephine Ramon

Key words to describe the project: In vitro electrophysiology, potassium channels

Description of the work:

Aims: To find novel medicine in spider venoms

Summary: Potassium channels are protein located in the cell membrane in order to let potassium flux. They are key players in the repolarization of cells during nerve signalling. They represent numerous drug targets. In a project funded for 4 years by the French Agence Nationale pour la Recherche, we are looking for channel blockers within the peptides diversity of spiders’ saliva glands.

In order to find these blockers, we embedded these potassium channels in vitro in an artificial lipid bilayer and we measure the flux and blockage of potassium ion through these proteins. Several key steps have been secured in order to get this fine electric activity recording in place: the in vitro synthesis and purification of these proteins and their insertion in liposomes.

The student will have to optimize Kv1.5 activity recording and to test venom fractions in order to look for cardiac arrhythmia inhibitors.

Experimental techniques:

Proteoliposomes production from protein synthetized in vitro.

Electrophysiology

Skills required: biochemistry and interest to work at the single molecule level.

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Research project 3: Designing novel anti-inflammatory drugs by targeting the CD domain of the MAP kinase p38α

Supervisor’s name 1: Mattew Bowler [email protected]

Supervisor name 2 (in case of absence): Gordon Leonard [email protected]

Lab: EMBL and ESRF

Administrative contact: Regis Lengrand

Key words to describe the project: Drug design

Description of the project:

The MAP kinase p38α is a central player in the activation of the inflammatory response. Phosphorylation by upstream kinases on a specific TxY motif leads to the activation of p38α which is then able to activate a series of transcription factors. It has therefore become the subject of intense study for novel small molecule modulators of inflammation. This kinase is an excellent target for the development of high throughput automatic fragment screening pipelines on the ESRF/EMBL beamline MASSIF1. We seek to identify novel inhibitors of the D-motif binding site, an allosteric regulatory site, for a new class of lead compounds with potential anti-inflammatory effects by soaking crystals of p38α with small molecule fragment libraries.

The project will provide training in many techniques required in drug lead identification and optimisation, including protein expression and purification as well as crystallisation. Soaked crystals will be sent to the MASSIF beamlines for automatic data collection, the student will then evaluate data sets for potential small molecule binding.

Skills required: This will involve training in X-ray crystallography and would suit a biochemist or physicist.

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Research project 4: Commissioning of, and first experiments on, the new instrument for in situ studies of nanoparticles and nanowires during their elaboration, using synchrotron X rays at the ESRF

Supervisor name 1: Gilles Renaud, [email protected]

Supervisor name 2 (in case of absence, holidays): Frédéric Boudaa, [email protected]

Lab: INAC / SP2M NRS

Administrative contact: Frédérique Garçin

Key words to describe the project: Nanowires; synchrotron; Molecular Beam Epitaxy, Chemical Vapour Deposition; in situ; Ultra-High-Vacuum

Description of the project:

The elaboration of nano-objects (quantum boxes, nano-wires, nanocatalysts…) for nano-electronics or catalysis uses growth methods such as Molecular Beam Epitaxy (MBE) or Chemical Vapor Deposition (CVD) which are thus fundamental to master, both technically and fundamentally. On the European Synchrotron Radiation Facility (ESRF) in Grenoble, we run an X-ray beamline coupled to an MBE/CVD Ultra-High-Vacuum (UHV) chamber, dedicated to the investigation by X-ray scattering of the structural properties (structure, shape, size, composition, organization, correlations…) of nano-materials during their elaboration by MBE and/or CVD. This instrument will be completed renewed during the 2014/2015 winter, thanks to funding by the French “Investissements d’Avenir” program. The proposed training stay will consist in participating in the final commissioning steps of the instrument and in the first test experiments. These will consist in growing Si/Ge nanowires of the highest quality, while investigating their structural properties, as well as undergoing research on supercooling of metal-semiconductor catalysts following a previous study published in Nature.

Research project 5: Probing the flexibility in the complement proenzyme C1r2C1s2 of innate immunity by cryo-electron microscopy

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Supervisor’s name 1: Wai Li Ling; [email protected]

Supervisor’s name 2: Guy Schoehn ; [email protected]

Lab: IBS

Administrative contact: Joséphine RAMON; [email protected]

Keywords: electron microscopy, single particle analysis, multivariate statistical analysis, immunology, complement

Description: This project studies a flexible protein complex C1r2C1s2 of the innate immune system using cryo-electron microscopy (EM). The isolated tetramer C1r2C1s2 forms an elongated chain in solution but folds to bind its partner protein C1q in the C1 complex. Upon target recognition by C1q, C1r2C1s2 undergoes a conformational change and activates the complement cascade that eliminates pathogens and flawed self-components. This activation is also involved in various autoimmune and inflammatory diseases. Determining the flexible domains in C1r2C1s2 will shed light on how the tetramer folds within C1 and how it changes conformation upon activation.

Our EM facility is well equipped with three FEI microscopes – a T12, a F20, and a 300 kV Polara. By analyzing cryo-EM images of the free C1r2C1s2 molecule taken with the new direct detector on the Polara, we aim to align the rigid central domain in the tetramer, whose structure has been solved, and study the flexibility of the neighbouring domains with multivariate statistical analysis.

Skills required: Background in physics, mathematics/statistics, or molecular biology as well as experience in linux and scripting is desired. Interest in electron microscopy, structural biology, and immunology is welcome. Self-motivation and diligence is valued.

Research project 6: Self-assembling protein-based bionanowires

Supervisor name 1: Dr. Vincent Forge

Supervisor name 2: Dr. Patrice Rannou

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Phone: +33-4-3878-9405

Email: [email protected]

Phone: +33-4-3878-2749

Email: [email protected]

Laboratory 1: CEA-Grenoble/DRT/iRTSV/CBM/AFFOND

Laboratory 2: CEA-Grenoble/DSM/INAC/SPrAM/LEMOH

Administrative contact (for HR matters) @ Laboratory 1:Nathalie Chaumery

Phone: 04-3878-9102. Email: [email protected]

Keywords to describe the project: Bioelectronics, Protein design & engineering, Self-assembling protein, Electronic & Ionic transport

Description of the project (aims, experimental techniques, recommended background):

Electron transport through proteins is a central mechanism of life, involved in production, storage, and use of energy in many biological processes[1]. The recent discovery of conduction in bacterial nanowires have opened doors to a protein-based electronics[2-3]. If understood and mastered, it could trigger a myriad of high tech applications making use of biosourced or genetically engineered (synthetic biology) active biomaterials.

The aim and ambition of this project are to understand and control the fundamental processes responsible for electronic transfer occurring across multiple (nano/micro/meso/macro-scopic) length scales in a model system specifically chosen for allowing a direct triple correlation in between its chemical structure, programmed self-assembly into high aspect ratio micro/nano-wires of known atomic structure and electronic transfer ability. The identified model systems, i.e. wild type and genetically modified nonpathogenic amyloid fibers (see Figure), will allow unprecedented in depth studies of the complex relations linking their structure and dynamics with their ionic and electronic transport abilities. Disentangling ionic from electronic transport contributions and identifying the relevant electron transport mechanisms at work within the core and periphery of the high aspect ratio amyloid fiber model systems will be the main scientific targets.

With a preferred (bio)physics background, the enrolled undergraduate student will join a multidisciplinary team uniting biologists (production of engineered proteins and biophysics), (electro)chemists (nanowire functionalization, connection to electrodes), (bio)physicist (electronic transport) and (nano)technologists (integration of bionanowires into devices). She/he will benefit from the state of the art technological & characterization platforms available within the MINATEC campus to develop her/his project under the supervision of Dr. V. Forge & Dr. P. Rannou.

Bibliography

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[1] N. Amdursky et al. Adv. Mater. 2014, 26, 7142. [2] C. Pfeffer et al., Nature 2012, 491, 218. [3] N.S. Malvankar et al., Nat. Nanotech 2014, 9, 1012

Research project 7: Energy Efficient Integrated Circuits for Brain Computer Interface systems

Supervisor’s name 1: Franck Badets ; [email protected]

Supervisor’s name 2: Stéphanie Robinet ; [email protected]

Lab: CEA-LETI DACLE/LEGECA

Administrative contact: Catherine Bour; [email protected]

Keywords: Brain Computer Interface – CMOS integrated Circuits – Impedance measurement – stimulation

Description of the project:

Brain Computer Interface (BCI) electronics systems are considered by scientific community as a possible way to compensate for handicap of heavily disabled persons. CEA-LETI and University Joseph Fourier of Grenoble are stakeholders of CLINATEC a state-of-the-art, unique in Europe clinic dedicated to brain studies and BCI implants located in CEA enclosure. CEA-LETI has already designed a BCI implant which consists in a discrete system composed of a full custom Analog Front End, a microcontroller, a power management unit and an RF link [1] [2]. Next generation of BCI implants should embed electrical stimulation to increase performances by bringing sensory feedback in a closed loop way.

The proposed internship will contribute towards the fully silicon integration of an electrical stimulation circuit by designing key blocs of an optimized architecture already patented by CEA-LETI [3].

[1]A. Eliseyev, T. Aksenova, C. Mestais, A.-L. Benabid, et al., CLINATEC BCI platform based on the ECoG-recording implant WIMAGINE and the innovative signal-processing to control the exoskeleton EMY: preclinical results, EMBC, 36th Annual International Conference of the IEEE, 2014

[2] Robinet, S., Audebert, P., Régis, G.& all. (2011). A Low-Power 0.7 32-Channel Mixed-Signal Circuit for ECoG Recordings. Emerging and Selected Topics in Circuits and Systems, IEEE Journal on, 1(4), 451-460

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[3] DUPONT, Florent, BECHE, Jean-Francois, CONDEMINE, Cyril, et al. Devices for electrical stimulation of a biological tissue and method for calibrating same. U.S. Patent Application 13/888,780, 7 mai 2013.

Skills required: Knowledge of analog electronics, simulation tools are required, and basic knowledge of CADENCE IC tools would be appreciated.

Research project 8: Theoretical prediction of stable B and N-doped C60 and their synthesis pathways

Supervisor’s name 1: Pascal Pochet

Lab: INAC (CEA)

Key words: Fullerene and graphene-like materials; Density functional theory; Potential energy surface exploration

Description of the project:

The raise of nano-science has promoted a lot of research efforts to find alternative fullerene materials that might be used as building block in the so-called bottom-up approach. In this study we will focus on N-doped C60 fullerene that have been synthesised 10 years ago [1] and on their boron counterpart as well. The attendee will perform an exhaustive exploration of the potential energy surface for this fullerene in order to check their synthesizable character using the proposed criterion in our last publication [2]. The second step will be to used the ART method [3] in order to find possible growth routes for the identified building block as recently proposed for boron cages [4]. The exploration will be performed at the DFT level using the BigDFT package [5] developed in Grenoble. Besides these important studies in cluster science, the attendee will have the possibility to develop experience in ab initio simulations on massive parallel supercomputers, which is a powerful investigation tool widely used both for basic or applied research.

[1] L. Hultman et al. Phys Rev Lett. 87 225503 (2001).

[2] S. De et al. Phys. Rev. Lett. 106, 225502 (2011).

[3] E. Machado et al. J. Chem. Phys. 135, 034102 (2011)

[4] P. Pochet et al. Phys. Rev. B 83, 081403(R) (2011).

[5] http://inac.cea.fr/L_Sim/BigDFT/

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Research project 9: Capillary microfluidics: achieving valving of spontaneous capillary flows by electro-capillary means.

Supervisor name 1: Jean Berthier ; [email protected]

Supervisor name 2: David Gosselin

Lab: DTBS/SBSC/LBAM

Keywords: capillarity, electro-capillarity, valves, metallic electrodes

Description of the project:

In biotechnology, biology and medicine, low-cost, portable systems are gaining momentum. Point-of-care systems (POC) and home-care systems are increasingly used. Using the patient blood—droplet taken at the tip of a finger—they will allow for detection of metabolites (cholesterol, glucose, thyroid hormones), viral load, and cell counting (haematocrit level).

These fluidic systems are actuated by capillary and surface tension forces. The ultimate goal is to reach the same sensitivity as laboratory instruments. Hence, progressively their sophistication is increasing, and there is a need to develop new capillary functions on such chips.

Valving is perhaps the most difficult fluidic function to master for portable systems. We propose to use a minimal electric energy source—that of a mobile phone for example—and an adequate geometry to actuate valving using electro-capillarity.

The theory of electro-capillarity is known since Lippmann, and the approach is mostly experimental. The candidate will develop the deposition of metallic electrodes in the micro-channels walls with the connection to the energy source, and find the geometrical designs that produce the stop of the flow under no-electric actuation conditions, and the release of the flow under low-voltage conditions.

Research project 10: Optical spectrometer for trace detection of NO in breath analysis

Supervisor’s name: Irène Ventrillard; [email protected]

Lab: Liphy (Joseph Fourier University)

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Administrative contact: [email protected]

Keywords: laser spectroscopy, high finesse cavity

Description: The LAME group of the LIPhy is well known in France and abroad for being at the fore front in the development of ultrasensitive spectroscopic techniques for selective and quantitative measurements of molecules present in a gas at very low concentration (trace detection). By the coupling of a laser to a high finesse optical cavity, the effective absorption length is enhanced up to dozens of kilometers while the actual cavity length is less than one meter allowing for a compact set-up for in-situ measurements. The group has developed an original technique called Optical Feedback-Cavity Enhanced Absorption Spectroscopy (OF-CEAS) that relies on the sensitivity of a semi-conductor laser to optical feedback, enabling the design of a compact instrument with very high detection sensitivity and very high molecule specificity, and a very small gas sampling volume. Additional advantages are that the method does not require routine calibration with certified gas mixtures and that the resulting robust instruments can be operated by non-specialists in a medical environment.

The student will study fundamental effects associated with the combination of OF-CEAS with QCLs. In particular, due to the strong absorption of the molecular lines in the MIR, the power broadening effect of intensity saturation has to be understood quantitatively. Another effect that will be studied is the impact of residual optical interference fringes on the spectrum normalization process. This effect is often more important in a QCL setup than in the traditional DFB setup, and it too requires a better characterization. These studies will involve both experiments and simulations.

Skills required: The candidate will have basic knowledge of optics and spectroscopy and an interest in instrumental developments. Knowledge in Labview software is suited.

Research project 11: Novel tools for the identification of small molecule –protein interactions.

Supervisor name 1: Jose A. Marquez; [email protected]

Supervisor name 2 (in case of absence): Irina Cornaciu ; cornaciu@embl

Laboratory: Marquez Team, European Molecular Biology Laboratory (EMBL)

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Administrative contact : Dominique Lancon ([email protected]) , Regis Lengrand ([email protected] )

Keywords to describe the project: Structural Biology, Protein crystallography, High Throughput, automation. Fragment screening,

Description of the project:

Structure-Guided Drug Design (SGDD) approaches are systematically incorporated in drug development campaigns in the pharmaceutical industry. There is a growing demand among academic groups in applying these techniques both for the identification of inhibitors and effector molecules, and as a key step to facilitate the transition from basic research to translational research. However, such approaches are manpower intensive, which limits the number of compounds that can be analyzed at a structural level. The goal of this project is to develop novel approaches for the identification of small molecule-protein interactions integrating both chemical and structural screening methods based on innovative technology recently developed at EMBL. This approach will be applied to the identification of small molecules targeting proteins of biomedical relevance.

Research project 12: Influence of neighbouring dielectric on the performance of UHF RFID Tags – survey and enhancement

Supervisor name 1: Dominique Vicard

Supervisor name 2 (in case of absence): Emmanuel Arène Phone: +33(0)6 3320 3710

Email: [email protected]: +33(0)7 7790 3930

Email: [email protected]

Start-up: Primo1D/CEA

Administrative contact (for HR matters): Dominique Vicard (see above)

Keywords to describe the project: RFID UHF experimental environment improvement antenna

Description of the project (aims, experimental techniques, recommended background):10 to 15 lines

This project aims at having a clear picture of the influence of the neighboring materials (textile, water, skin) on a set of UHF RFID tags used for traceability and referencing in a connected object framework. In textile (which is the primary market for the Primo1D

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startup) several sectors among which the industrial laundry and textile rental businesses are quickly moving to RFID solutions for the tracking of the textile assets they use or process. Several problems are still limiting the deployment of such solutions, among which the influence of the immediate surroundings of the RFID tag, which detunes the RFID antenna and therefore degrades the performances. The purpose of the internship is to first survey the behavior of RFID Laundry tags by benchmarking Primo1D’s tags and the tags from competitors with different kinds of perturbations, then designing and testing solutions for enhancing Primo1D’s E-Thread® tag performance. The experimental part will include measurements in anechoic conditions, and the use of a dedicated RFID tag measurement instrument. The prospective part will include RF simulations and microwave antenna design.

Research project 13: Theory of spin-photon interfaces. Foundations and potential for quantum technologies.

Supervisor name 1: Alexia Auffèves

Phone: +33(0)456387011

Email: [email protected]

Supervisor name 2: Cyril Branciard

Email: [email protected]

Laboratory: Institut Néel, Nanophysics and semiconductors (NPSC) group

Administrative contact (for HR matters): Florence Pois, [email protected]

Keywords: quantum optics, quantum information, theory, modelling

Description of the project:

The main goal of the project is to model and investigate theoretically the potential of spin-photon interfaces for quantum information processing. Such devices consist of single spins coupled to light propagating in waveguides, or photonic circuits: in these so-called "one dimensional atoms", light matter interaction is so strong that the spin state leaves a macroscopic imprint on single photons having interacted with it. The spin-photon interface opens major perspectives for quantum physics and quantum information processing, such as Quantum Non Demolition measurement of the spin using a single photon, or the possible engineering of spin-photon entanglement. On the other hand, one-dimensional devices have a range of promising functionalities when embedded in a network, e.g. could provide efficient quantum gates, quantum repeaters, or light rectifiers.

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The candidate should have already taken courses in quantum mechanics. A experience in coding (Matlab, Mathematica), will be appreciated.

Research project 14: Microfluidic system for continuous cell culture

Supervisor name 1: RIVERA Florence Email: [email protected]

Laboratory: LETI DTBSAdministrative contact :

Keywords to describe the project:

Description of the project:

Within the Department of Technologies for Health and Biology, the Biochip and Biopackaging laboratory develops new microfluidic systems to address the field of cell therapy. One of the research objective is the development of microbioreactor for continuous cell culture [1]. Such microbioreactor can be used for various applications such as drug screening on cell culture, or autologous stem cell expansion chamber. First developments have been performed demonstrating cell viability during continuous cell culture. We now want to integrate on-line sensing in order to precisely control the cell culture condition.

The main objectives of the internship will be to first take in hand the current set-up, to validate first design improvements in term of fluidic and to design a new set-up to integrate biosensors for cell culture monitoring. Depending on the project progress, final validation will be performed on real condition, meaning cell lines culture in the microbioreactor.

[1] Abeille, F. et al. Continuous microcarrier-based cell culture in a benchtop microfluidic bioreactor. Lab on a Chip 14, 3510-3518, doi:10.1039/c4lc00570h (2014)

The candidate shall speak English (or French) and have good communication skills as he/she will have to work and report inside a collaborative team.

He/She shall possess a background in the field of physics/engineering, physics/chemistry, biomedical engineering. Knowledge in microfluidics and/or cell culture would be a plus. The candidate shall have an experimentalist profile and be highly motivated by multidisciplinary project.

Duration: 3-6 (preferred) months

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Research project 15: Characterization of the biochemical and biological functions of a chromatic factor

Supervisor name 1: Christel CARLES

Supervisor name 2 (in case of absence): Emmanuel Thévenon

Email: [email protected]

Email: [email protected]

Laboratory: Laboratoire de Physiologie Cellulaire Végétale, UJF

Administrative contact (for HR matters): Sophie Mistri ([email protected])

Keywords to describe the project: Chromatin Biology, Developmental Genetics in Plant

Description of the project:

The TRITHORAX (TRX) factor was first characterized in Drosophila as a modifier of chromatin that maintains developmental genes transcriptionally active, via trimethylation on Lysine 4 of Histone 3 (H3K4me3). Several TRX homologs have been identified since then, known as members of the SDG large family of proteins. Among them, the ATX3 (SDG14) protein of Arabidopsis has the peculiar feature to contain, on the top of the habitual PHD domains (for recognition of modified histone residues) and SET domains (the enzymatic modules for methylation), a SAND domain that is also found in the ULTRAPETALA1 (ULT1) protein studied in the lab. The SAND domain of several animal transcription regulators directly binds to the major groove of DNA. ATX3 thus stands as a protein with putative binary functions, directly interacting with both histones and DNA, and potentially equivalent to the ULT1 – ATX1 interacting module identified by our group. (i) The student will characterize ATX3 enzymatic function and Histone target residue. (ii) He/she will use atx3 loss-of-function Arabidopsis mutants to screen for defects in histonemethylation and to identify ATX3 function during development.

Research project 16: Fabrication of biocatalytic electrodes for bioenergy conversion using carbon nanostructures

Supervisor name 1: Michael Holzinger

Email: [email protected]

Supervisor name 2 (in case of absence): Alan Le Goff

Email: [email protected]

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Laboratory: Départment de Chimie Moléculaire UMR 5250

Administrative contact (for HR matters): Régine Rozand ([email protected])

Keywords to describe the project: Biofuel Cells, Carbon nanostructures, Enzymes, Electrocatalysis, Bioelectrodes

Description of the project (aims, experimental techniques, recommended background):10 to 15 lines

The goal of this internship is to evaluate different approaches to form efficient biocatalytic electrodes for the glucose biofuel cell applications. A common strategy for glucose fuel cells development is to use enzymatic catalysts – e.g. glucose oxidase at the anodic side and laccase or bilirubin oxidase at the cathodic side. The overpotential, specificity and the catalytic activity of these biological catalysts are much more interesting than noble metals in aerated glucose solutions at neutral pH values. However, enzymes have a limited stability, depending on the environment in which they are used (temperature, pH, inhibitors...) and their active centers are often deeply embedded in the protein structure which makes the electron transfer difficult. The use of electron shuttles, called mediators, can drastically increase the yield of wired enzymes but reduces the output voltage of the fuel cell.

The objective of this internship is to optimize the connection between the redox active site of the enzyme and the electrode based on a porous matrix of carbon nanotubes or graphene. The grafting of these enzymes to these nanomaterials using a biocompatible polymer or a binder, acting as a mediator, will increase the efficiency of electron transfer between the enzyme and the electrode. The candidate should have a background in electrochemistry and in the manipulation of nanomaterials. He (she) will get an insight to the approaches used to form such porous nanostructures and to realize enhanced electron transfer between the redox enzymes and the nanostructures

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Research project 17: Intrinsically disordered Proteins: how do they work?

Supervisor’s name 1: Martin Blackledge

Email: [email protected]

Supervisor’s name 2 (in case of absence, holidays): MALENE RINGKJOBING JENSEN

Lab: Protein Dynamics and Flexibility by NMR, Institut de Biologie Structurale

Administrative contacts:

Joséphine RAMONTél : 33 (4) 57 42 86 96Email : [email protected] :

Dominique RibeiroTél : 04 57 42 85 61Email : [email protected]

Key words to describe the project: High field nuclear magnetic resonance spectroscopy, intrinsically disordered proteins, protein dynamics, conformational flexibility, protein folding upon binding, free-energy landscape

Description of the considered work (aims, experimental techniques, recommended background):

Proteins are inherently dynamic, exhibiting conformational freedom on timescales from picoseconds to seconds, implicating structural rearrangements essential for function. Nuclear Magnetic Resonance spectroscopy is sensitive to conformational fluctuations occurring on all time-scales, and in my group we develop methods to quantitatively describe these motions and to determine their role in biological function. Intrinsically disordered proteins (IDPs) have no stable fold, and represent extreme examples where protein flexibility plays a determining role in function. We are currently developing approaches to study the behaviour of IDPs from NMR data in vitro and in vivo, and to apply these to describe the formation of dynamic complexes in IDPs involved in human disease, for example viruses and neurodegenerative disease. The project will involve the measurement of atomic resolution structural information from IDPs using state of the art high field NMR equipment (600, 700, 850 and 950MHz are available in the lab). The project is suited to physical chemists or biochemists or biophysicists. We look forward to your application, in the meantime here is

Research projects for international students – GIIP 2015

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some more information about the lab: http://www.ibs.fr/groups/protein-dynamics-and-flexibility/

Skills required:Physical chemists, biochemists, biophysicists or physicists are welcome to apply. Basic knowledge of NMR, biophysics, molecular dynamics simulation or experience in working with intrinsically disordered proteins would be an advantage (but absolutely not essential).

Maximum duration (if you are able to welcome the student beyond July 25): 6 months

Research projects for international students – GIIP 2015