Institut Necker Enfants Malades (INEM) is a biomedical research center located on the Hôpital Necker-Enfants Malades campus. It benefits from numerous state-of-the-art core facilities. The Campus has a long-standing reputation for scientific excellence and key pioneering medical contributions (transplantation, biotherapy, gene therapy). It provides a vibrant environment for basic research and translational innovation.

The host laboratory

The Immunity in Health and Disease team, led by Simon Fillatreau investigates the roles of B and T cells in autoimmune and infectious diseases, with a particular emphasis on identifying and characterizing novel pro-inflammatory and anti-inflammatory T cell, B cell and plasma cell subsets. Their research seeks innovative approaches to restore immune regulation in humans. They place particular emphasis on the roles of CD4+FOXP3+ regulatory T cells (Tregs) and B cells in maintaining this balance.

The project

INEM U1151 is the coordinator of an Horizon Europe (HE) project, financed by the European Commission, starting in July 2023 for a duration of 5 years. 

Type 1 diabetes (T1D) is a chronic autoimmune disease, often beginning in childhood, caused by the immune-mediated destruction of insulin-producing pancreatic beta cells. Current standard-of-care treatment relies primarily on insulin replacement and therefore addresses the consequences of the disease rather than the underlying autoimmune process. With the incidence of T1D increasing, particularly among young children, there is a major unmet need for innovative therapies capable of targeting the disease at its immunological root.

Our goal is to develop a cell therapy based on TCR-engineered regulatory T cells (Tregs) for the treatment of T1D in humans. Rather than simply controlling the metabolic consequences of the disease, this strategy aims to selectively suppress the pathogenic immune response responsible for beta-cell destruction.

This work is part of ARTiDe, a European collaborative project coordinated by S. Fillatreau. ARTiDe brings together eight partners and combines complementary technologies for the systematic identification of autoantigen-specific Tregs and effector T cells in humans, the selection of optimal T-cell receptors (TCRs) to generate protective Tregs, innovative humanized preclinical models of T1D to assess efficacy and safety, the development of scalable processes for the production of TCR-engineered Tregs, and novel strategies to support Treg function in vivo.

More information about the consortium is available at artide.eu.

Mains activities: Within the ARTiDe consortium, you will develop and evaluate TCR-engineered Tregs as a novel cell therapy for T1D, using an innovative humanized model of the disease that allows for direct translation of the findings to the human system.

The project will investigate newly identified TCRs isolated from human insulin-reactive regulatory T cells for their capacity to produce protective Tregs in this model, with the objective of selecting the most promising candidate for future clinical translation. The work will combine Treg engineering and functional characterization with in vivo preclinical studies.

In parallel, you will conduct mechanistic investigations to define the mode of action of adoptively transferred TCR-engineered Tregs in the humanized T1D model, providing insight into how antigen-specific Tregs control pathogenic immune responses and protect pancreatic beta cells.

Your profile

We are looking for a highly motivated and creative scientist with a PhD in immunology or a related field and a strong interest in translational immunology and cell therapy.

Candidates should be self-motivated, well organised, and able to work both independently and collaboratively; have strong communication and scientific writing skills, with fluency in English; be able to work effectively in an international and multicultural environment.

Experience with experimental mouse models is essential.

Expertise in one or more of the following areas would be particularly valuable:

• Cellular immunology and T-cell biology
• Regulatory T-cell biology
• Multicolor flow cytometry
• Mouse models of autoimmune disease
• Primary T-cell culture and functional assays
• Genetic engineering of T cells, particularly using retroviral vectors

Experience with type 1 diabetes models, humanized mouse models, or adoptive cell therapy would be an additional advantage but is not required.

The positition is funded for 1 year. Salary will be according to experience following INSERM regulation.

How to apply

Interested applicants should send:

• A cover letter describing their research background, motivation for the position, and future research interests
• A curriculum vitae, including a list of publications
• Contact information for three referees

Applications should be sent by email to Simon Fillatreau : @email / @email 

Start date

As soon as possible