Contacter Valérie Castellani
Childhood malignancies of the nervous system: exploring the dissemination of tumoral cells in light of the mechanisms of the embryonic development
We are looking for a highly motivated post-doc to join us on a project at the interface of developmental biology and childhood cancerology. Our lab is interested in understanding the mechanisms providing topographic landmarks to migrating cells and axons during the wiring of the nervous system. In parallel we study how childhood cancers with embryonic occurrence take advantage of the mechanisms of the embryonic neuro-development, with a focus on the metastatic dissemination. We are mainly working on neuroblastoma, a pediatric cancer that arises from a transitory embryonic cell population, the neural crest. We developed an in vivo model consisting in implanting human malignant cells at the site of the neural crest origin in the chicken embryo (Delloye-Bourgeois et al, Cancer Cell, 2017). Combined with different types of imaging (videomicroscopy, light sheet confocal microscopy) and transcriptomic approaches, it allowed us to characterize various cellular and molecular dialogs between malignant cells and their embryonic environment. We recently extended our approaches to study another pediatric cancer, the medulloblastoma.
The project aims at characterizing shared and unshared behaviors of malignant cells with their cells of origin labeled by specific fluorescent reporters, focusing on migratory processes. The objectives are to compare cell behaviors using imaging techniques and transcriptomic analyses to identify signaling pathways governing the pathfinding strategies of malignant cells during their dissemination.
MeLiS is composed of seven teams using a diversity of models, from c elegans, zebrafish, drosophila, chicken and mouse, and addressing biological questions at the molecular, cellular and organism levels. We share strong interest for cell biology and imaging approaches. The NeuroMyoGene Institute is located at the core of hospitals and research centers in cancerology and neuroscience, in a living place accessible by public transport, at 10 min from the heart of the city.
We invite candidates with the following profiles to apply:
- Acquired skills in developmental biology, in vivo manipulations and molecular biology, imaging. Knowledge of the chicken embryo model would be a great plus. or
- Acquired skills in transcriptomic approaches (single cell RNAseq and data analysis) applied to developmental biology and/or cell lineage studies.
We wish to recruit a post-doc with excellent interpersonal and communication skills, good work ethics, strong motivation and creativity. Fluency in English is mandatory but ability to speak French is not required. The project is funded by a grant from ARC (Association pour la recherche sur le Cancer) to the lab, for 3 years. Salary will depend on previous experience. Applications should contain a CV, a letter of motivation with a description of research accomplishments and the contact information of two references to firstname.lastname@example.org.
Contact Owen Randlett
A zebrafish model of Autosomal Recessive Cerebellar Ataxia 2 for drug discovery and phenotypic prediction.
The student will join our group studying the neural basis of behaviour in larval zebrafish at the MeLiS Unit of the Institut NeuroMyoGene in Lyon, France. We combine genetic approaches, quantitative behavioural assays, and neural circuit imaging approaches to uncover the mechanisms underlying behaviour and its plasticity in the brian, and how these processes go awry in the context of disease. The student will work on the ANR-funded project (TREATCOQ), which is a collaboration with the Puccio Group in the PGNM Unit of the Institut NeuroMyoGene.
Autosomal-recessive cerebellar ataxia (ARCA) is a heterogeneous group of >100 rare degenerative and metabolic genetic diseases that share the common hallmark of progressive damage of the cerebellum and associated tracts. COQ8A-ataxia (ARCA2), characterized by slowly progressive cerebellar ataxia, combined with variable features including developmental delay, cognitive impairment, epilepsy, dystonia and myopathic features, is due to loss of function mutations in ADCK3/COQ8A. Currently, no viable treatments exist for ARCA2 patients.
The aims of this project are:
- To characterize a new zebrafish model of ARCA2 using Cas9-targeted mutagenesis, behavioural assays, neuroanatomical phenotyping, and functional imaging.
- To develop high-throughput screens to identify small molecules that are able to rescue disease-associated phenotypes, with the hope of discovering novel therapeutic candidates to test in mammalian models.
- To use genetic approaches to recapitulate patient-specific mutations in order to attempt to uncover a logical mapping between genotype and disease phenotype to aid in disease prognosis and individualized treatment.
Candidates are expected to have a background in neuroscience or molecular biology, though alternative backgrounds will be considered. Familiarity with Python and/or other data analysis approaches, and a desire to develop novel assays and analyses are highly valued. Fluency in English is mandatory, French is not. Application should be sent to email@example.com with the subject line: “PhD-treatcoq”, including a CV, a 1-page motivation letter detailing why you are interested and a good fit for this project and our team, and arrange for 3 letters of reference to be sent directly.