Duration: 4 to 6 months (between January and September 2021)

Description of the host team:
Mosaic is an interdisciplinary research group aiming at unravelling life science problems using advanced photonic tools. Mosaic principal investigators are physicists and biologists working together at the cross roads between advanced optical imaging, nanophotonics and tissue morphogenesis. In parallel, the Mosaic group is involved in collaborative projects related to the fields of developmental biology, immunology, neurosciences and biomedical research.
Web page: https://www.fresnel.fr/spip/spip.php?article1418

Description of the environment:
The research at Institut Fresnel covers a very large spectrum, tackling such diverse fields as electromagnetism theory, information processing, image analysis, advanced imaging and life sciences. At Institut Fresnel, the MOSAIC team (see above) gathers approximately 40 students and postdocs, which makes the environment very international and particularly stimulating for an internship.

Description of the internship project:
Animal development critically relies on the migration of groups of cells, able to move over large distances and fuse with target tissues. How cell intrinsic factors and external cues are integrated to precisely guide collective migration of cells is still poorly understood. The objective of the internship is to decipher the feedback between positional information and migration that leads to the refined guidance of massive groups of cells, using Drosophila metamorphosis as a model system. The student will take part in a multidisciplinary effort that includes cutting-edge imaging, developmental biology, biophysics and theory. In line with the centuri summer school on quantitative biology, she/he may focus on the acquisition of quantitative time-lapse movies of the process, and the development of image analysis pipeline to quantify the flows underway during migration. More emphasis may be given to experiments or analysis depending on the background and motivation of the student.

Interdisciplinarity and disciplines involves:
The project is interdisciplinary by nature as it implies:

• Cell and developmental biology
• Biophysics and imaging
• Image analysis
• Genetics, to perturb the biological processes at play.

The students will have the opportunity to use techniques such as cutting edge optical imaging or optical manipulation of cells and tissues (opto-genetics, laser ablation). The student will interact with collaborators working on optical engineering as well as modeling.

Expected profile:
The student may either have a background in cell and developmental biology and a desire to tackle problems from a quantitative standpoint or a background in engineering/physics with a desire to address biological questions.

Contact:
Location of the internship : Institut Fresnel – Marseille – France
Head of internship :
Loïc Le Goff : loic.legoff@fresnel.fr ((+33)4.13.94.55.07), Equipe Mosaic

Duration: 3 months

Description of the host team:
Antibodies are lifesaving biomolecules – major effectors of vaccines efficacy and powerful therapeutics for cancer treatment. In natural immunity, highly potent antibodies are produced by the descendants of a single antigen-specific B cell after complex processes of cellular and molecular maturation. Our laboratory gathers expertise in cellular immunology, single-cell genomics, and bioinformatics, to decode B cell immune responses in health and disease.

Description of the environment:
The Integrative B cell Immunology lab is part of the Center for Immunology of Marseille-Luminy (CIML), a public research institute gathering 16 research labs focusing on all aspects of the immune system. CIML is located on the Luminy campus at the gates of the Calanques National Park, in Marseille, France. CIML provides state-of-the-art technologies for immunology and genomics research, and access to high performance computing for bioinformatics and big data analyses.

Description of the internship project:
Single-cell genomics have emerged as a powerful tool to study heterogeneous functional programs in complex organs. Bioinformatics analyses of rich single-cell RNA-seq (scRNA-seq) datasets have allowed the identification of new cell types and functional subsets, and have permitted to reconstruct cell differentiation trajectories a posteriori from snapshot data. The scRNA-seq method is uniquely suited to study B cells in immune responses.
We have developed methods for integrative single-cell analyses of phenotype, B cell receptor mutations, and transcriptome in B cells and their clonal progeny, in order to produce high-resolution single-cell models of cellular and molecular changes in mouse and human B cell subsets during immune responses. In the frame of that research program, the intern will be involved in data production (experimental biology) and/or data analysis (computational biology).

Interdisciplinarity and disciplines involves:
Experimental immunology, single-cell genomics, bioinformatics, statistics and machine learning.

Expected profile:
The expected candidate has a strong interest in both immunology and data science, looking to apply bioinformatics and machine learning methods to decode the complexity of immune responses in healthy and disease context. Experience in programming with R or Python is required.

Contact:
milpied@ciml.univ-mrs.fr

Duration: 3 to 4 months

Description of the host team:
We develop and apply advanced force spectroscopy techniques to unravel the physics behind biological systems, from single molecules to membranes and living cells.
Our research is based on atomic force microscopy (AFM) and emerging technologies such as acoustic force spectroscopy (AFS) and deformability cytometry (DC).

Description of the environment:
Our laboratory is developping experimental approaches and applying physical concepts to achieve a quantitative understanding of molecular and cellular mechanics from a fundamental point of biew but with an eye on applying our approches to the clinic.
Our interdisciplinary and international group integrates members coming from physics, chemistry, engineering, and biology backgrounds.

Description of the internship project:
Receptor-ligand interactions are at the root of all biological function in living cells. Streptavidin-biotin interaction leads to one of the strongest non covalent bond known. This interaction has been widely studied and used to attach various biomolecules to each other or to a solid support, or to detect or purify proteins. This project aims at exploring this interaction at ultra slow loading rate using an emerging technique, named Acoustic Force Spectroscopy (AFS), recently implemented in our laboratory. AFS is making use of acoustic pressure waves to pull or push hundreds of particles or cells and track them simultaneously. Therefore, it allows highthroughput force measurements on individual biomolecules and thus gives access to low loading rates, sub-pN forces and long timescales, unviable by other force spectroscopy techniques. We will use this technique to explore the energy landscape of the streptavidin biotin complex, using specific DNA tethers. The results will be succeptible to publication.

Interdisciplinarity and disciplines involves:
physics, biochemistry

Expected profile:
We are looking for a student with a strong background in physics or engineering and an interest in biophysics. Programming skills will be a plus. The internship could be potentially followed by a PhD thesis.

Contact:
felix.rico@inserm.fr ; claire.valotteau@inserm.fr

Duration: Any period from January to August 2021.

Description of the host team:
Jean-François Rupprecht leads the Out-of-equilibrium Mechanics (OM) team within the Centre de Physique Théorique (Aix-Marseille University, Luminy campus). The OM team is reinforced by 2 post-doctoral researchers: N. Tizon-Escamilla & S.-Z. Lin – in close contact with experimental biophysics groups, including P.-F. Lenne & B. Ladoux groups. We will also interact the computational group of a new CENTURI PI - Philippe Roudot.
See https://centuri-livingsystems.org/jf-rupprecht/ and https://www.normalesup.org/~rupprecht/

Description of the environment:
A large proportion of cancers come from epithelial tissues whose function is to protect inner organs. Our objective is to build an algorithm to infer the mechanical properties of these epithelial tissues based on optical images. As the rigidity of a tissue can be used as a clinical criterion for the recognition of pre-cancerous tissues, such algorithm could provide a new clinical insight to live endoscopies.

Description of the internship project:
At the OM theory group, we aim at understanding the physics of living materials based on analytical (e.g. active liquid crystal theories) and numerical models, e.g. vertex model, whereby the overall tissue dynamics results from the mechanical balance between a set of representative cellular forces – namely, viscous resistance, interfacial tension and cellular pressure (see image below).
We put a strong emphasis on understanding the role of out-of-equilibrium fluctuations in tissue dynamics. These are now increasingly recognized as playing a crucial role in controlling whether a material is rigid and elastic, or soft and fluid; yet, so far, the contribution of active force fluctuations has been significantly overlooked in tissue mechanics models. To fill this gap, we propose new out-of-equilibrium statistical physics tools that are predictive, shedding new lights on the role that local biochemical perturbations can play in the global mechanical tissue properties.
During this internship, we propose to use our fluctuating vertex model - with well-controlled mechanical properties - to expand the capability of a deep learning code currently developed in the team with the objective to infer mechanical properties of our simulated tissues. A second phase of the internship will consist in the exploitation of our trained deep-learning tool on in vitro tissue data.

Interdisciplinarity and disciplines involves:
Deep Learning, Active Biological Matter, Out-of-equilibrium Statistical Physics.

Expected profile:
Physics major and/or engineering-major student

Contact:
rupprecht@cpt.univ-mrs.fr / rupprecht.jf@gmail.com

Duration: 4 months

Description of the host team:
Monocytes and macrophages play an essential role in tissue homeostasis, inflammation and immunity. We are studying the mechanisms controlling proliferation and cell fate decisions during monocyte differentiation, from hematopoietic stem cells to mature cells. We are interested in understanding the transcriptional regulation, with a particular focus on the transcription factors, of cell self-renewal and reprogramming in mature macrophages, and role of monocyte/macrophage subtypes in inflammation and tissue regeneration.

Description of the environment:
We are a team of 7: 3 permanent researchers, 1 PhD student, 1 research engineer in biological experimentation and 1 bioinformatician engineer who will be the direct supervisor of the trainee.
Sieweke's team is an european leader in the study of blood stem cells and macrophages (key cells of innate immunity) and is a expert user of modern genomic tools (RNA-seq, ATAC-seq, ChIP-seq, nanofluidic qPCR).

Description of the internship project:
RT-qPCR is a technology of choice for the quantification of the expression of a given gene. However, our research topics require the quantification of the expression of a wide range of genes in a large number of samples simultaneously. Microfluidic systems coupled with nanotechnology-based signal detection devices are now part of the molecular analysis landscape (Coelho et al., 2017). The raw data at the output of the analysis device (Biomark) cannot be used as it stands.
The aim of this project is to develop a web interface or a "user-friendly" graphical interface allowing automated processing with options (choice of genes/samples to be filtered, choice of normalisation, etc...) and generating graphical representations that can be easily customised by the user (likely to be published at a later date), thus freeing him/her from the difficulties of interaction with programming languages.
The languages used to built the tool will be HTML, CSS, PHP, Javascript, JQuery, R/Shiny, Python/Dash.

Interdisciplinarity and disciplines involves:
Programming using HTML, CSS, PHP, Javascript, JQuery, R/Shiny, Python/Dash.

Expected profile:
The difficulty of the project is the creation of the graphical interface and therefore requires strong programming skills. Biology skills are not necessary but an interest in the field is required.

Contact:
sarrazin@ciml.univ-mrs.fr

Duration: 3 to 6 months

Description of the host team:
The intern will be directly mentored in complementary ways by Thomas MARISSAL (PhD, INSERM researcher at the Mediterranean Institute of Neurobiology, INMED) for the biological part of the project and Lucas GOIRAND-LOPEZ (PhD candidate) for the bioinformatic component. Other enthusiastic researchers from the INMED, specialized in a specific field, will be occasionally involved for the different stages of the project.

Description of the environment:
The internship will take place at the Mediterranean Institute of Neurobiology (Aix-Marseille University), an architectural jewel headed by Dr. Rosa Cossart with the spectacular Parc des Calanques as a backdrop. INMED is a top-level neuroscience research center, hosting 9 research groups investigating the development and the malfunction of neuronal circuits using mouse models and cutting-edge techniques.

Description of the internship project:
Temporal Lobe Epilepsy (TLE) is the most prevalent type of epilepsy in adults. The disease manifests as the occurrence of unpredictable and recurrent seizures and severe disorders of mood and cognitive functions. Using rodent models, we, and others, have been pointed out several alterations of the hippocampal circuit, including a degeneration of both inhibitory and excitatory neurons, accompanied by the acquisition of aberrant intrinsic properties by survivor cells, as well as a reorganization of the synaptic network. We would like to build a scale-down in-silico version of the epileptic hippocampus, based on experimental data. The aim is to understand better the pathological impact of each molecular/cellular alterations on the network dynamics related to cognitive or mood function.

Interdisciplinarity and disciplines involves:
That multi-disciplinary project involves several fields in biology, physics, mathematics and bioinformatics. More specifically, the intern will perform programming/coding using Matlab and Python. The intern will also have the opportunity to familiarize with various tools in preclinic research including mouse genetic models, optogenetic and/or glutamate uncaging-based manipulation of neurons, single cell electrophysiological patch-clamp recording, network calcium imaging, behavioral testing, etc.

Expected profile:
We are looking for a talented and highly motivated student, eager for teamwork, and who followed a training in programming/coding and bioinformatics. Notions in Neuroscience would be a bonus (but not mandatory). On the other hand, the supervisors guarantee to the intern an inspiring, pleasurable and enriching environment, which will place him or her in the ideal condition for quickly progressing and learning.

Contact:
thomas.marissal@inserm.fr