GIANT International Internship
programme:
Summer 2015 research projects
kfield
17/12/2014
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 ; sophie.mistri@cea.fr
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 plantspecific 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 ; beatrice.schaack@ibs.fr
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 mbowler@embl.fr
Supervisor name 2 (in case of absence): Gordon Leonard leonard@esrf.fr
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, gilles.renaud@cea.fr
Supervisor name 2 (in case of absence, holidays): Frédéric Boudaa, frederic.boudaa@esrf.fr
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 nanoelectronics 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.
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Research project 5: Probing the flexibility in the complement
proenzyme C1r2C1s2 of innate immunity by cryo-electron
microscopy
Supervisor’s name 1: Wai Li Ling; wai-li.ling@ibs.fr
Supervisor’s name 2: Guy Schoehn ; guy.schoehn@ibs.fr
Lab: IBS
Administrative contact: Joséphine RAMON; josephine.ramon@cea.fr
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.
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Research project 6: Self-assembling protein-based bionanowires
Supervisor name 1: Dr. Vincent Forge
Phone: +33-4-3878-9405
Email: vincent.forge@cea.fr
Supervisor name 2: Dr. Patrice Rannou
Phone: +33-4-3878-2749
Email: patrice.rannou@cea.fr
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: Nathalie.chaumery@cea.fr
Keywords to describe the project: Bioelectronics, Protein design & engineering, Selfassembling 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 selfassembly 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
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(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
[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 ; franck.badets@cea.fr
Supervisor’s name 2: Stéphanie Robinet ; Stephanie.robinet@cea.fr
Lab: CEA-LETI DACLE/LEGECA
Administrative contact: Catherine Bour; Catherine.bour@cea.fr
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
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[2] Robinet, S., Audebert, P., Régis, G.& all. (2011). A Low-Power 0.7 32-Channel MixedSignal Circuit for ECoG Recordings. Emerging and Selected Topics in Circuits and Systems,
IEEE Journal on, 1(4), 451-460
[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).
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[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/
Research project 9: Capillary microfluidics: achieving valving of
spontaneous capillary flows by electro-capillary means.
Supervisor name 1: Jean Berthier ; jean.berthier@cea.fr
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 microchannels 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.
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Research project 10: Optical spectrometer for trace detection of
NO in breath analysis
Supervisor’s name: Irène Ventrillard; irene.ventrillard@ujf-grenoble.fr
Lab: Liphy (Joseph Fourier University)
Administrative contact: sabine.gustave@ujf-grenoble.fr
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.
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Research project 11: Novel tools for the identification of small
molecule –protein interactions.
Supervisor name 1: Jose A. Marquez; marquez@embl.fr
Supervisor name 2 (in case of absence): Irina Cornaciu ; cornaciu@embl
Laboratory: Marquez Team, European Molecular Biology Laboratory (EMBL)
Administrative contact : Dominique Lancon (dlancon@embl.fr) , Regis Lengrand
(lengrand@embl.fr )
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
Email:
Dominique.vicard@primo1D.com
Phone: +33(0)7 7790 3930
Supervisor name 2 (in case of absence):
Emmanuel Arène Phone: +33(0)6 3320
3710
Email:
Emmanuel.arene@primo1D.com
Start-up: Primo1D/CEA
Administrative contact (for HR matters): Dominique Vicard (see above)
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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
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
Foundations and potential for quantum technologies.
interfaces.
Supervisor name 1: Alexia Auffèves
Phone: +33(0)456387011
Email: alexia.auffeves@neel.cnrs.fr
Supervisor name 2: Cyril Branciard
Email: cyril.branciard@neel.cnrs.fr
Laboratory: Institut Néel, Nanophysics and semiconductors (NPSC) group
Administrative contact (for HR matters): Florence Pois, florence.pois@neel.cnrs.fr
Keywords: quantum optics, quantum information, theory, modelling
Description of the project:
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The main goal of the project is to model and investigate theoretically the potential of spinphoton 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.
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: Florence.rivera@cea.fr
Laboratory: LETI DTBS
Administrative 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)
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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
Research project 15: Characterization of the biochemical and
biological functions of a chromatic factor
Supervisor name 1: Christel CARLES
Email: Christel.carles@ujf-grenoble.fr
Supervisor name 2 (in case of absence):
Emmanuel Thévenon
Laboratory: Laboratoire de Physiologie
Cellulaire Végétale, UJF
Administrative contact (for HR matters):
Sophie Mistri (Sophie.mistri@cea.fr)
Email: Emmanuel.thevenon@cea.fr
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
histone
methylation and to identify ATX3 function during development.
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Research project 16: Fabrication of biocatalytic electrodes for
bioenergy conversion using carbon nanostructures
Supervisor name 1: Michael Holzinger
Email: michael.holzinger@ujf-grenoble.fr
Supervisor name 2 (in case of absence): Alan Le Goff
Email: alan.le-goff@ujf-grenoble.fr
Laboratory: Départment de Chimie Moléculaire UMR 5250
Administrative contact (for HR matters): Régine Rozand (Regine.Rozand@ujf-grenoble.fr)
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: martin.blackledge@ibs.fr
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 RAMON
Tél : 33 (4) 57 42 86 96
Email : josephine.ramon@cea.fr
or :
Dominique Ribeiro
Tél : 04 57 42 85 61
Email : Dominique.Ribeiro@ibs.fr
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
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the
meantime
here
is
some
more
information
http://www.ibs.fr/groups/protein-dynamics-and-flexibility/
about
the
lab:
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
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