Internship Master: Study of mechanisms and conditions of nucleation of ice

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Thesis offert: Nanoscience in translation

Graduate School: Natural and Engineering Sciences

PhD programme: Nanoscience and Advanced Technologies

Application Deadline: 16 April 2018

Start Date: 1st October 2018

Duration: 36 months

The PhD programme in Nanosciences and Advanced Technologies aims at coordinating a wide research area focussed on nanoscience where the most recent and innovative technologies in physical chemistry are exploited to target translational research with special reference to the biomedical field. An extensive range of scientific expertise, technology, and effort is dedicated to the following objectives: Synthesizing and characterising innovative nanomaterials, Establishing reliable screening procedures to evaluate nanomaterials and nanovectors safety in vitro and in vivo, Assessing nanovectors validity for theranostics with general aim at “Developing biomimetic nanomaterials with active targeting properties and their in vitro and in vivo assay”

Among the main themes for this application area, the applicants should focus on:
•Synthesis of biomimetic polymeric nanoparticles active in recruiting a defined protein corona composition.
•Assay of nanomaterial and nanovectors in cell cultures for toxicity, subcellular targeting and distribution, storage and degradation, and biological effect.
•Assay of nanomaterial and nanovectors in laboratory animals for toxicity, organ targeting and biodistribution, and biological effect.

Research proposals covering the themes above are invited. Priority will be given to multidisciplinary projects.


INFO For further information about the research topics
, please, contact Prof. Franco Tagliaro (franco.tagliaro@univr.it) and Giovanna LOLLO (giovanna.lollo@univ-lyon1.fr)

PhD thesis offer between :
Université Lyon 1, LAGEP, 43 Boulevard du 11 Novembre 1918, Bâtiment CPE
69622 Villeurbanne Cedex, France
and
University of Verona. Dep.Neurosciences, Biomedicine and Movement Sciences,(Italy)

PhD “Design and development of new gene delivery systems for the treatment of autoimmune diseases”

PhD thesis offer
Université Lyon 1, LAGEP, 43 Boulevard du 11 Novembre 1918, Bâtiment CPE
69622 Villeurbanne Cedex, FRANCE

Title: “Design and development of new gene delivery systems for the treatment of autoimmune diseases” – 3 years under the supervision of Prof. Stephanie Briancon and Dr. Giovanna Lollo
Contact : Dr Giovanna Lollo giovanna.lollo@univ-lyon1.fr, Prof. Stephanie Briancon stephanie.briancon@univ-lyon1.fr
Keywords: Nanocarriers, mRNA (messenger ribonucleic acid), biomaterials, lipids, physico-chemical characterization, myeloid derived suppressor cells, in vivo studies
Starting date: April 2018
Laboratory: The LAGEP (Laboratoire d’Automatique et de Génie des Procédés) is a research laboratory of the University Lyon 1 and the French national Institute for scientific research (CNRS UMR 5007). It develops pluridisciplinary research in chemical engineering, pharmaceutical engineering and biochemical processes. The LAGEP gathers strong pluridisciplinary competences in close collaboration with national and international research and development centers in industry or in academia. The “pharmaceutical engineering” group has its strong expertise in drug delivery. The research encompasses several scientific domains as development of new drug delivery systems, physical chemistry properties, biological in vitro evaluation, in vivo biodistribution and efficacy in mice models.

Subject: We are looking for a motivated and pro-active student to be part of an international academic/industrial European project in Gene therapy working closely with high renowned research groups and one of the leader companies in Gene therapy worldwide.
The role of the PhD student will be to design, characterize, produce and evaluate novel nanomedicines for the delivery of genetic material (mRNA) for human applications.
Specific tasks of the student will involve:
i) the design and formulation of intelligent nanoparticulate systems based on either FDA approved materials or new chemical entities to ensure the correct biodistribution of the systems in vivo;
ii) the evaluation of different ingredients on the formulation to warrant the right intracellular activity and delivery of the mRNA;
iii) the modification the selected formulations to provide them targeting properties for tissue/cell specific delivery;
iv) the evaluation of the association, integrity and activity of the encapsulated/associated genetic material.
The student will interact with other students and researchers of the consortia to establish research lines, communicate and discuss the achieved results.
We offer a full industrial/academic training in the formulation and evaluation of nanosystems for drug delivery. Full support on the development of nanoparticles and in vitro evaluation. Training in basics of molecular biology analytics (mRNA quantification, characterization, identification and lab-manipulation) and an international and innovative working group.

Required skills:
- A master degree in Pharmaceutical sciences or Molecular biology.
- Knowledge on genetics or molecular biology is a plus.
- Hands on experience with advance analytical and bioanalytical techniques such as HPLC, electrophoresis, Western blot.
- Hands on experience on cell culture or working under aseptic conditions for the manipulation of the mRNA.
- A very strong chemical background and preferentially experience in conducting small chemical reactions on polymers or particles.
- Basic knowledge of GMP working conditions.
- A very innovative spirit and willing to be part of a multicultural and multidisciplinary environment
- A self-motivated person able to think “out of the box” and having a “problem-solving” approach
- Good presentation skills
- Fluent English and French
Please send to giovanna.lollo@univ-lyon1.fr and stephanie.briancon@univ-lyon1.fr the following documents:
- CV,
- motivation letter,
- two recommendation letters.

Internship: decoupled EDP applied to wastewater treatment

Scientific Officer: DOS SANTOS MARTINS Valérie
valerie.dos-santos-martins@univ-lyon1.fr
Co-Manager in Grenoble : CADET Catherine, GIPSA-Lab
Catherine.Cadet@gipsa-lab.grenoble-inp.fr

Laboratory of Scientific Bearer: LAGEP
Laboratory (s) or partner team (s) LJK (G.-H. Cottet (E. Maitre), LEGI (P. Séchet), Catholic University of Louvain (Denis, DOCHAIN, Belgium), GIPSA-Lab (CADET Catherine)
Project title Modeling and Simulation of Settling in Dense Media: Application to a Secondary Decanter of a Wastewater Treatment Plant

Description of the subject
This project is intended to improve the operation of existing urban or industrial wastewater treatment plants. For these stations, the activated sludge process, simple to implement and very effective, remains the most widespread treatment method. On an existing treatment plant, the loads to be treated (pollution and flow rates) increase steadily while pollutant discharge standards are more and more restrictive, which causes difficulties in stabilizing the operation of the station. It also results in a quantity of sludge produced such that the usual methods of disposal or recovery of sludge which are no longer sufficient. A stabilization of the operation, in spite of the variability in flow rate and concentration of the effluents to be treated, also makes it possible to obtain sludge of constant quality which would make the sedimentation phenomenon more reliable and falling down. This last one is a central phenomenon of the activated sludge process and its performance has a major impact on the entire treatment. Much research has been done to improve the monitoring of treatment plants, and there are currently internationally recognized models for the operation of biological reactors. However, there is currently no satisfactory model for secondary settlers. The models currently presenting the best compromise between the complexity and the representability of the phenomena are the 1-D models. They rely on flow theory: horizontal velocity profiles are considered uniform and horizontal concentration gradients negligible. Therefore only the vertical dimension is modeled.
The most widely used model is Takács’ model (Takács et al., 1991), based solely on a mass balance. Important phenomena such as diffusivity or compression are not taken into account. Simulation of this model requires the introduction of an empirical expression of the sedimentation rate. The parameters are usually determined by empirical equations that use laboratory sedimentation tests such as Sludge Velocity Index (SVI). The equation is a nonlinear hyperbolic partial differential equation, of which not all phenomena are mastered. Some attempts to improve this model have been proposed (Cadet et al., 2015). A diffusivity term, which allows to stabilize the numerical simulation has been added, as the conservation moments equation. These equations are based on the theory of sedimentation-consolidation of particulate suspensions, which require the definition of two phases: a liquid phase and a solid phase. A change of scale of modeling is then necessary, going from the preceding macroscopic assessment to a balance of the forces at the level of the flocs. The definition of these forces requires the introduction of parameters and functions that must be explained. A difficulty is that these functions or parameters are discontinuous depending on the height in the decanter. In addition, in the existing work, a semi-empirical expression of the sedimentation rate was defined for each zone, thus decreasing the relevance of the model to represent the physical phenomena. This way of solving the problem leads to obtaining both hyperbolic and parabolic equations according to the zone.

Work to be done:
Our challenge is to solve the model consisting of a system of two partial differential equations, the mass balance allowing determining the concentration of the sludge at the exit of the clarifier and the conservation equation of the moments, making it possible to determine dynamically the speed of sedimentation. In addition, being able to determine the height of the mud web is also a challenge since the sedimentation and compression zones are of variable volume. Finally, with a view to using the model in a control strategy of the decanter or the activated sludge process, it is necessary to use only a reasonable and representative number of parameters.
The modeled phenomena, the formalism of the partial differential equations of the model (equations, initial conditions, boundary conditions) as well as the parameters used (discontinuity or continuous functions) will be defined.
The requested work consists in checking the adequacy of the model with the objectives of use: physical properties, mathematical, reduction of model or not, system well posed or not, stability and / or stabilization, controllability, parametric sensitivity, dependence on the boundary conditions and initial conditions.
Since this model is non-linear, it will be necessary to simulate it to determine some of its properties. This point may be the subject of a project continuation.

Skills: EDP, Appetites for Process Engineering, Autonomy

Expected results and prospects
At the end of this project, a dynamic model of the secondary clarifier will be established, validated in a simple case. It will be possible to consider other larger projects, which both deepen the development of numerical methods and make it possible to turn to applications for the control:
• on the decanter itself: this will allow to control the concentration of sludge extracted despite variations in the input concentration. It will also be possible to explore the use of the decanter for dynamic storage purposes, ultimately allowing the volume of the decanters to be optimized.
• on the whole activated sludge process: a relevant control strategy must be done throughout the process and not only at the level of the biological reactor. The monitoring of floc formation in the biological reactor and on their settling is not currently explored.

Project location: Lyon with meeting in Grenoble.
02 or 03-2018 +6 months
Possibility of thesis in Grenoble

Internship offer: Characterization of material transfer processes and adsorption / desorption of antibodies / antigens in a biological diagnostic device by the affinity chromatography technique.

Proposition de stage

Titre

Caractérisation des processus de transfert de matière et d’adsorption/désorption d’anticorps/antigènes dans un dispositif de diagnostic biologique par la technique de la chromatographie d’affinité.

Contexte

Les systèmes de diagnostic in vitro permettent d’identifier l’origine d’une maladie à partir d’échantillons biologiques prélevés sur un patient. Les immunoessais, l’une des technologies utilisée pour les systèmes de diagnostic in vitro, permettent de détecter ou de quantifier la présence d’antigènes ou d’anticorps dans un échantillon biologique. Ils reposent sur le principe de la réaction immunologique : la reconnaissance spécifique entre un anticorps et un antigène.
Les mécanismes physiques mis en jeu lors des différentes étapes d’un test d’immunoessai sont nombreux et dépendent beaucoup des conditions expérimentales. Les processus de test complets sont donc extrêmement complexes et ne sont pour l’instant mis au point que par une approche essentiellement empirique, donc coûteuse en temps et en ressources.
Afin d’améliorer et de concevoir les systèmes de diagnostic de façon plus rationnelle et efficace, il y a donc un intérêt fort à apporter une compréhension fine et une vision intégrée de l’ensemble des mécanismes mis en jeu dans les tests. Focaliser le travail empirique de conception et d’optimisation sur des paramètres critiques pré-identifiés par un modèle prédictif aurait donc un impact direct sur l’efficacité de développement de nouveaux systèmes ou tests, voir sur la performance des tests eux-mêmes.

Dans ce cadre, une collaboration a été établie entre le LAGEP et la société bioMérieux dans la mesure où les processus physico-chimiques se produisant dans les dispositifs de diagnostic concernés relèvent du Génie des Procédés : il s’agit de processus de transfert de matière et d’adsorption/désorption.
Un outil expérimental composé d’une colonne contenant un lit fixe de particules a été mis en place afin d’étudier les phénomènes physico-chimiques mis en jeu lors des tests d’immunoessais. Parallèlement, un modèle dynamique de l’outil expérimental prenant en compte les processus de transfert de matière a été développé et implémenté avec le logiciel Matlab. Ces outils expérimentaux et de modélisation sont utilisés i) pour affiner notre connaissance des mécanismes impliqués dans la capture d’antigènes par des anticorps immobilisés sur des surfaces et ii) identifier les paramètres critiques des systèmes de diagnostic.

Le travail se fera au LAGEP, Laboratoire d’Automatique et de Génie des Procédés (LAGEP-UMR CNRS 5007) et plus particulièrement au sein de l’équipe Dynamique et Commande des Procédés (DYCOP) dont les thématiques de recherche concernent, entre autres, la caractérisation et la modélisation des phénomènes de transfert de matière dans les milieux poreux.
Ce travail se fait en collaboration avec la société bioMérieux (Laurent Drazek – Laurent.DRAZEK@biomerieux.com)


Description du stage
Durant ce stage il s’agira :
-d’utiliser et d’améliorer l’outil expérimental mis en place pour étudier les phénomènes physico-chimiques mis en jeu lors de la capture d’antigènes par des anticorps immobilisés sur un support.
Des anticorps seront immobilisés sur un lit de particules dans une colonne. Des antigènes seront injectés à l’entrée de la colonne de chromatographie. La concentration en antigène sera mesurée en sortie de colonne pour obtenir des courbes de perçage. L’influence de certains paramètres (tels que le débit et la concentration d’antigènes en entrée de colonne) sur les courbes de perçage devra être étudiée.
-d’exploiter les courbes de perçage obtenues pour caractériser les paramètres physico-chimiques intervenant dans les interactions anticorps/antigènes. Les paramètres seront obtenus en minimisant l’écart entre les données expérimentales et les données de simulation obtenues grâce au modèle déjà implémenté sous Matlab.

Profil recherché
- Niveau d’étude : niveau master 2 ou troisième année d’école d’ingénieur.
- Qualités requises : organisation, rigueur, motivation, travail en équipe, goût pour l’expérimentation.

Compétences
- Compétences en analyses physico-chimiques ;
- Connaissances en génie des procédés ;
- Connaissances de base en immunologie appréciées mais pas obligatoires.

Lieu
Laboratoire LAGEP (UMR CNRS 5007, Université Lyon 1)
Bâtiment CPE
43 boulevard du 11 novembre 1918
69 100 VILLEURBANNE

Durée proposée
6 mois (1er semestre 2018 – dates flexibles)

Conditions d’accueil
Le stagiaire sera co-encadré par Maëlenn Robin et Mélaz Tayakout-Fayolle au sein de l’équipe DYCOP du LAGEP.
Gratification de stage : gratification légale (~3.60 €/heure soit ~500€/mois)

Contact
Merci d’envoyer vos CV et lettres de motivation à Maëlenn Robin (maelenn.robin@etu.univ-lyon1.fr – 04 72 43 18 70).