Junior Professorship in human brain organoid modeling of rare neurodevelopmental disorders

The Junior Professorships opened to Inserm are intended for researchers with strong potential to manage and lead research teams and participate in national, European or international projects.

This recruitment, based on research and teaching projects, is aimed at researchers with a doctorate or equivalent. The position is offered on a fixed-term contract (CDD) with a view to tenure in the Inserm Research Directors personnel at the end of the contract.

Name of the project:

From human brain organoid modeling of rare neurodevelopmental disorders to personalized medicine

Anticipated duration of the contract: 3 years

Scientific domains: Neurobiology – Rare Genetic Neurodevelopmental Disorders

Location: Genetics of Developmental Anomalies (GAD) Team – UMR 1231 Inserm – University of Burgundy – Genomic and Immunotherapy Medical Institute (GIMI) – Dijon – France

Strategy of the host institution:

The Genetics of Developmental Anomalies team (GAD – https://www.gad-bfc.org) is a part of FHU TRANSLAD (http://www.translad.org/en), which is one of the medical and scientific teams at the head of the Genomic and Immunotherapy Medical Institute (GIMI – http://www.gimi-institute.org/en). For many years, Inserm has invested in research on rare diseases (RD) by coordinating major national and international research programs, i.e. the European Joint Program on Rare Diseases (EJP RD) and the “Programme Prioritaire de Recherche Maladies Rares (PPR-RD)”. Inserm also coordinates the “Plan France Médecine Génomique 2025” in a care-research continuum designed to allow reanalysis of genomic data from hundreds of thousands of RD patients in the national “Collecteur Analyseur de Données” (CAD) for research purposes. Through the EJP RD, Inserm has implemented a system of governance to ensure that France’s strategy remains aligned with the national strategies of the European Commission, the 35 other countries involved, and the other major participants such as industry partners. Inserm is now recognized as a major European player in the field of rare diseases. In Dijon, the UMR1231, which is a collaboration between Inserm and the University of Burgundy (9 teams, more than 270 people), has extensive experience in multidisciplinary research. UMR1231 is a unit that combines fundamental and clinical research and that has a high potential to publish in leading international journals and to transfer its findings rapidly into the clinical setting. This also translates into an excellent fundraising record and the ability to grow, with the recruitment of permanent positions including research fellows and research supervisors.

Strategy of the host laboratory:

Within the UMR1231, the GAD team is focused on developing an innovative translational research project. The objectives of this new project are to identify new gene-phenotype associations responsible for rare neurodevelopmental disorders (NDDs) and to implement genomic medicine with a focus on new technologies, reducing the diagnostic odyssey, understanding the physiopathology of NDDs, developing expertise in coordinating therapeutic trials, and participating in prominent European projects.

Thanks to its close relationship with FHU TRANSLAD, the national French “Rare Disease Healthcare Network” (AnDDI-rares) and the “Grand Campus BIOME” bioinformatics platform of the University of Burgundy, the GAD team is part of a very dynamic framework dedicated to personalized medicine and rare diseases. The GAD team also hosts the NeuroGeMM team whose work is directed at understanding the neurobiology and the genetics of mammalian brain development in health and disease. Therefore, one of the four scientific axes of the GAD team is devoted to functional genomics and physiopathology, based on mouse and innovative cellular models such as human iPSCs and brain organoids. In this context, the team leads the PPR-RD MultiOmixCare project, including one full-time engineer and one technician who will work full time with the successful candidate. The aim of the professorship is to support and intensify this work, while consolidating the existing dynamic.

Summary of the scientific project:

NDDs are challenging to model in vitro because relevant patient-derived tissues are not available. For this reason, our laboratory invested in the implementation of reprogrammed neurons and astrocytes derived from patient-derived induced pluripotent stem cells (human iPSCs), as well as in the 3D cultures of brain organoids, to study the molecular mechanisms underlying pathophysiological changes. Our approach makes it possible to investigate the cellular and molecular changes underlying pathogenic genetic variants in candidate genes of interest. Cutting-edge techniques such as single-cell RNA-seq, spatial transcriptomics, electrophysiology (MEA technology), and epigenomics explorations are currently deployed in our laboratory to characterize neurons, astrocytes and human brain organoids.

Our current field of interest includes, but it is not limited to, the study of splicing factors involved in NDDs and the phospohatidylinositol-3,4-biphosphate kinase PIK3CA. The personalized cellular models used in our laboratory will also make it possible to carry out preclinical studies for the screening of molecules in ultra-rare diseases to open up perspectives in the therapeutic trials for patients suffering from NDDs. The selected candidate will work within the existing framework but is also expected to develop his/her own research on NDDs.

Summary of the teaching project:

The selected candidate will be expected to teach classes at the “Environnement et Santé” (E2S – https://e2s.ubfc.fr/) doctoral school of the University of Burgundy, particularly in the field of system biology and cellular models for neurodevelopmental disorders. The selected candidate will also participate in the teaching of master’s students within the Life Sciences and Health Sciences department of the University of Burgundy.

National Research Agency package:

200k€ + one research engineer and one laboratory technician already available for 5-year

term

Scientific communication and dissemination:

The selected candidate will be encouraged to actively promote their results and define the target audience (representatives of patient organizations, healthcare professionals, researchers, industry, funding agencies). He/she is also expected to publish his/her results in high-level international scientific journals and present at international conferences (ASHG, ESHG, etc.).

Open Science:

The selected candidate will comply with the current policies of INSERM and the University of Burgundy regarding Open Science practices, in particular:

– Providing open access to scientific publications and research data under the principle “as open as possible, as closed as necessary”, including access to information about the research tools and instruments needed to validate or re-use our data; open access code for the CT designs and models that will be proposed and developed during this project;

– Responsible management of research data in line with the FAIR principles through the use of a data management plan (DMP).

– Deposit of all the scientific productions from the chair in the national HAL archive, like the productions of the host laboratories;

– Publication of “pre-prints” (e.g., via biorxiv.org);

– Pre-registration of studies (“pre-registered reports”);

– Data sharing with the whole community via OSF (Open Science Framework);

– Use of GITHUB-type servers for the distribution and sharing of software and data analysis procedures.

Science and society:

GAD team members are fully committed to sharing their research with the public through participation in national events (i.e. The European Researchers’ Night, Telethon, Rare Disease Day), local events (e.g. Experimentarium program) and through special GAD initiatives (e.g. lab open house events, visits to primary schools, etc…)

The team is part of an effort to increase the visibility of career paths in genetics (i.e. scientific and medical professions) among secondary school students through laboratory open days, the development of several communication tools such as books and videos, and close collaboration with the PEMR (Plateforme d’Expertise Maladies Rares) and its network of patient associations.

Selection of candidates:

Successful candidates are chosen by a selection commission composed of six to ten members,

the majority of whom are specialists in the fields of research concerned.

The commission carries out an initial examination of the applications, focused in particular on candidate experience and skills relative to the research and teaching project presented above. A shortlist of candidates is then selected for interview. Only candidates selected by the selection committee on the basis of their applications will be invited to interview.

The interviews are followed by a deliberation during which the selection commission will discuss the quality, originality and, where appropriate, the interdisciplinarity of the research and teaching projects presented by the candidates, their motivation and their scientific and teaching supervision capacity.

The candidates selected at the end of the selection process will be offered a junior professorship contract, following approval from the President and CEO of Inserm.

For more information, interested candidates can contact Prof Christel Thauvin-Robinet (christel.thauvin@chu-dijon.fr).