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
Research project 2: From gene to potassium channel blockers
Research project 3:Designing novel anti-inflammatory drugs by targeting the CD domain of the MAP kinase p38α
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
Research project 5: Probing the flexibility in the complement proenzyme C1r2C1s2 of innate immunity by cryo-electron microscopy
Research project 6: Self-assembling protein-based bionanowires
Research project 7: Energy Efficient Integrated Circuits for Brain Computer Interface systems
Research project 8: Theoretical prediction of stable B and N-doped C60 and their synthesis pathways
Research project 9: Capillary microfluidics: achieving valving of spontaneous capillary flows by electro-capillary means.
Research project 10: Optical spectrometer for trace detection of NO in breath analysis
Research project 11: Novel tools for the identification of small molecule –protein interactions.
Research project 12: Influence of neighbouring dielectric on the performance of UHF RFID Tags – survey and enhancement
Research project 13: Theory of spin-photon interfaces. Foundations and potential for quantum technologies.
Research project 14: Microfluidic system for continuous cell culture
Research project 15: Characterization of the biochemical and biological functions of a chromatic factor
Research project 16: Fabrication of biocatalytic electrodes for bioenergy conversion using carbon nanostructures
Research project 17: Intrinsically disordered Proteins: how do they work ?
Research project 1: Understanding the role of SEPALLATA3 splice variants in flower development
Supervisor’s name: Chloe Zubieta
Lab: LPCV
Administrative contact: Sophie Mistri;
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
Research project 2:From gene to potassium channel blockers
Supervisor’s name: Beatrice Schaak ;
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.
Research project 3:Designing novel anti-inflammatory drugs by targeting the CD domain of the MAP kinase p38α
Supervisor’s name 1: Mattew Bowler
Supervisor name 2 (in case of absence): Gordon Leonard
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.
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,
Supervisor name 2 (in case of absence, holidays): Frédéric Boudaa,
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
Supervisor’s name 1: Wai Li Ling;
Supervisor’s name 2: Guy Schoehn ;
Lab:IBS
Administrative contact: Joséphine RAMON;
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
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Supervisor name 1: Dr. Vincent Forge
Supervisor name 2:Dr. Patrice Rannou
Phone: +33-4-3878-9405
Email:
Phone: +33-4-3878-2749
Email:
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Laboratory 1: CEA-Grenoble/DRT/iRTSV/CBM/AFFOND
Laboratory 2: CEA-Grenoble/DSM/INAC/SPrAM/LEMOH
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Administrative contact (for HR matters) @ Laboratory 1:Nathalie Chaumery
Phone: 04-3878-9102. Email:
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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
[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 ;
Supervisor’s name 2: Stéphanie Robinet ;
Lab: CEA-LETI DACLE/LEGECA
Administrative contact: Catherine Bour;
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
[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]
Research project 9:Capillary microfluidics: achieving valving of spontaneous capillary flows by electro-capillary means.
Supervisor name 1: Jean Berthier ;
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;
Lab: Liphy (Joseph Fourier University)
Administrative contact:
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.