Deciphering the mutational signatures by genetics, genomics and microfluidics

A 2-year post-doctoral position in genetics, genomics and microfluidics funded by a grant from ITMO Cancer (Aviesan, Inserm) is open in the group of Dr. Julie Soutourina at I2BC, CEA/Saclay (Paris region, France), in close collaboration with Dr. Florent Malloggi (LIONS, CEA/Saclay).
The post-doctoral fellow will participate in the interdisciplinary collaborative project to improve our understanding of the mutational processes at the origin of cancers. We aim in deciphering the impact of transcription and DNA repair combined with mutagen exposure on mutational processes in human cancers using a combination of genetic, genomic, microfluidic and computational approaches. We propose to take advantage of the yeast model to perform large-scale mutational experiments and to identify the most mutagenic combinations of genetic background and mutagen treatment that will be then directly tested in human cells. A novel methodological framework based on microfluidics, allowing to considerably accelerate mutation accumulation experiments in yeast by unprecedented parallelization that we recently developed, will be applied. A computational analysis of these experimental data will help to understand underlying mechanisms of mutational processes.
The successful candidate will have a PhD in molecular biology with solid knowledge in genetics and functional genomics. We are seeking for highly motivated candidates with a strong interest in the field of transcription and DNA repair in eukaryotes together with interdisciplinary approaches based on microfluidics. A previous experience on yeast model and DNA sequencing approaches will be important. Good communication skills in English or French are required.

Microfluidic biocatalysis

The overall objective of the project is to propose a new mode of biocatalytic production based on continuous flow and combining macro and micro-fluidics. The aim is to develop a biocatalysis process involving fluidic bioreactors capable of ensuring continuous biotransformation, thanks to immobilized enzymes or whole cell catalysts. This process will be optimized to improve the efficiency of enzymatic reactions on the one hand and to obtain important production capacities on the other hand. Two types of enzymes will be studied, nitrilases and ketoreductases.
First, the candidate will be responsible for the search for robust enzymes for the target reactions and screening on the defined substrates. He or she will be responsible for the development of reaction conditions in isolated enzymes and whole cells and the determination of apparent kinetics. Then, he/she will be in charge of setting up the biocatalysis operating conditions and the immobilization of the biocatalyst in versatile continuous reactors.
This subject is carried out between two departments of the CEA (Direction of Fundamental Research/IBFJ/Genoscope in Evry and Direction of Technological Research/Leti in Grenoble).
The candidate will work in pair with a PhD student on the design of the biocatalytic reactor and the scaling up of the biocatalytic process.

Post doctoral/Research engineer position in esophageal tissue engineering using bioprinting techniques

Due to disease such as cancer or accidents such as caustic burns, the esophagus is sometimes irreversibly damaged and the only option is to remove it and replace it by using the stomach and part of the digestive tract, which often leads to serious complications and even in the best cases to poor functional results and poor quality of life. The most advanced current developments in tissue engineering for the esophagus is the use of decellularized donor tissue and clinical trials are ongoing at St Louis Hospital in this area. This approach however still presents some limitations, in particular related to donor shortage and inflammatory response. In order to prepare the next generation approach, the lab initiated a project funded by MSD Avenir to build an esophagus substitute using 3D printing. This bottom-up approach which uses bioinks as a starting material allows full control over 3D architecture and the construct can be thus personalized to the patient’s morphology and pathology, including smaller sizes for pediatric patients, in unlimited supply which is a great advantage over donor tissue. We have patented a formulation based on both natural and synthetic polymers which shows similar mechanical properties when compared to native esophagi, good suturability as well as high porosity to allow cell colonization. It also presents slow degradation as the ultimate aim is that it be replaced with native regenerated tissue over time.

We are seeking a highly motivated and autonomous post-doctoral fellow or research engineer to continue this project and characterize long term culture on this scaffold by re-epithelializing the interior of the tube and seeding primary endothelial and muscular cells on the outer part. Characterizations will include both material mechanical testing and long term cell behavior, morphology and analysis of any toxicity.

Location; St Louis Hospital, Paris

Development of a cell analysis algorithm for phase microscopy imaging

At CEA-Leti we have validated a video-lens-free microscopy platform by performing thousands of hours of real-time imaging observing varied cell types and culture conditions (e.g.: primary cells, human stem cells, fibroblasts, endothelial cells, epithelial cells, 2D/3D cell culture, etc.). And we have developed different algorithms to study major cell functions, i.e. cell adhesion and spreading, cell division, cell division orientation, and cell death.
The research project is to extend the analysis of the datasets produced by lens-free video microscopy. The objective is to study a real-time cell tracking algorithm to follow every single cell and to plot different cell fate events as a function of time. To this aim, researches will be carried on segmentation and tracking algorithms that should outperform today’s state-of-the-art methodology in the field. In particular, the algorithms should yield good performances in terms of biological measures and practical usability. This will allow us to outperform today’s state-of-the-art methodology which are optimized for the intrinsic performances of the cell tracking and cell segmentation algorithms but fails at extracting important biological features (cell cycle duration, cell lineages, etc.). To this aim the recruited person should be able to develop a method that either take prior information into account using learning strategies (single vector machine, deep learning, etc.) or analyze cells in a global spatiotemporal video. We are looking people who have completed a PhD in image processing, with skills in the field of microscopy applied to biology.

Lensfree Cytometry for High-troughput biological analysis

The new lensfree imaging is against the foot of the recent developments in microscopy that focuses today on super-resolution achievements. Instead lensfree imaging offers several advantages: field of view (FOV) can cover several cm2, resolution in the range of 0.5µm to 3µm, mostly compact sizes and ease of use. The technique is based on holography online as invented by Gabor [1]. A biological object is illuminated by a coherent light, micrometric structures of the object diffract and the light interferes with the incident wave. The amplitude of the interference is recorded by a CMOS sensor and the image is reconstructed thanks to inverse-problem approaches. Albeit the method exists since 1970, the recent development of large field, small pixel size digital sensors helped realize the full potential of this method only since 2010.
At CEA-LETI Health Division, a new microscopic platform based on this principle has been developed. Its applicability for performing high-throughput monitoring of major cell functions such as cell-substrate adhesion, cell spreading, cell division, cell division orientation, cell migration, cell differentiation, and cell death have been demonstrated [2,3]. The new project proposed in this PostDoc is dealing with the development of an innovative lensfree cytometry setup aiming at high-throughput analysis of biological samples, e.g. cell counting, cell sorting, etc. The post-doctoral fellow will develop the instrumentation and methods and will conduct the experimentation and analysis of true biological samples.

Process evaluation of 3rd generation biofuel production from micro-algae

CEA contributes to R&D activities in 3rd generation biofuel production from micro-algae by its fundamental research in biology (understanding of biological mechanism and improvement of microorganism performances) led by DSV at CEA Cadarache. LITEN Institute, belonging to CEA/DRT, investigates 2nd biofuel generation, from studies on resources (biomass, waste) up to industrial, economical and environmental integration.
This post doc fellow will use the different approaches developed at LITEN/DTBH to :
- perform a prospective study on process integration, for biofuel production from micro-algae,
- realize a technico-economical study of the more promising process solutions in the 2rd generation domain and industrial use of micro-algae,
- estimate the environmental impact (especially CO2) of these processes.

This work will take place in in frame of a collaboration of both labs (DSV/IBEB and DRT/LITEN/DTBH), the first one bringing its very fundamental knowledge on technical ability and performance of the micro-organism, the second one giving the knowledge on process and technico-economical evaluation of industrial reactor systems.
The post doc fellow, located in Grenoble, will go as needed in Cadarache to discuss with biology experts.

Kinetic study of biocide effect in nanocellulose_based food film

This project will study the kinetic of biocide effect of a nanocellulose-based film food. The main aim is to graft Ag and/or ZnO NPs on and inside halloysite particles that have a characteristic shape of twisted sheets and therefore could acting as NPs tanks. The localization of NPs outside halloysite could induce a fast biocide effect with limited duration whereas the internal grafting could produce longer biocide effect. This project gathers all steps from the film food synthesis, its nanocharacterization to the evaluation of its toxicological effect on bacteria. The final goal is to find one or many halloysite functionalizations allowing to extend the biocide effect in film food and to transpose it to other types of materials.