Study of the ageing of the human myocardium using a digitally modelled organoid

The Curie Institute Research Center

The “Institut Curie” is a major player in the research and fight against cancer. It consists of a hospital and a Research Center of more than 1000 employees with a strong international representativeness.

The objective of the Curie Institute Research Center is to develop basic research and to use the knowledge produced to improve the diagnosis, prognosis, and therapeutics of cancers as part of the continuum between basic research and innovation serving the patient.

INSERM U932 Immunity and Cancer – Team Innate Immunity

Directed by Ana-Maria Lennon-Duménil, the "Immunity and Cancer" unit (U932) at Institut Curie is currently composed of 10 research teams (approx. 150 researchers), including the "Innate Immunity" team, led by Nicolas Manel. The team studies the mechanisms of self/non-self detection in innate and ageing immunity, and is composed of 1 CNRS researcher, 3 PhD students, 2 engineers, 1 bioinformatician, 1 visiting scientist and 7 postdocs. As all researchers at Institut Curie, team members have access to 19 state-of-the-art technology platforms, research support services and a training catalogue including scientific and soft skills courses.

4Dcell

4Dcell is an innovative French start-up that aims to revolutionize in vitro pharmacological testing to improve the efficiency of drug development while reducing the use of live animal testing. 4Dcell develops cell culture consumables that allow for better control of the cellular microenvironment. In collaboration with its partners, 4Dcell uses these solutions to design model organoids that facilitate the discovery of new drugs (immuno-oncological treatments, heart failure, liver diseases, neurological disorders).

PhD students will benefit from an interdisciplinary, international research environment at the interface between fundamental research and applications for the benefit of society.

Context

With the support of the Ile de France region, which is co-funding the thesis, we are opening a PhD student position at the "Life Sciences" doctoral school of the University Paris Sciences & Lettres (PSL). This project is integrated in a collaborative project centered on the study of myocardial ageing, between the U932 "Immunity and Cancer" research unit at the Institut Curie in Paris, the Paris Cardiovascular Research Center at the Hôpital Européen Georges Pompidou and the biotechnology company 4Dcell in Montreuil.

Population ageing represents a major medical and societal challenge. Even though the deterioration of the heart is one key factor in the ageing process, the biological mechanisms that control the ageing of this organ are still poorly understood. The aim of this PhD thesis project is to study the biological mechanisms involved in the ageing of the human heart through the use of the innovative SmartHeart cardiac organoid model.

Thanks to a collaboration between the Institut Curie, 4Dcell and the Paris Cardiovascular Research Center, this project will combine experimental approaches with modelling to simulate and test interventions aimed at slowing or reversing cardiac ageing. The three-year timeline includes the study of the effect of perturbations on the ageing of the SmartHeart, the construction of a digital twin using the obtained experimental data, and the evaluation of the geroprotective properties of chemical cocktails, paving the way for major advances in the cardiovascular health of the elderly.

Objectives

• Study the cellular and molecular ageing of the in vitro "SmartHeart" cardiac organoid developed by 4Dcell in collaboration with Prof. Jean-Sébastien Hulot's team at the Paris Cardiovascular Research Center, using genetic, biophysical or pharmacological perturbations.
• Building a non-destructive biological clock for the SmartHeart.
• Model the experimental data and behaviour of the SmartHeart to generate a digital twin.
• Use this digital twin to define and perform in vitro testing of pharmacological interventions having a positive or negative impact on the biological ageing of the SmartHeart.

Job specifications

The PhD student will carry out his/her thesis under the supervision of Dr Nicolas Manel, and will be seconded 70% of his/her time to the 4Dcell site in Montreuil (93100), under the co-direction of Dr Christophe Pannetier, Scientific Director.

Training, experience and skills required

This opening is aimed at a student with skills in cellular and/or molecular biology and programming, wishing to develop or acquire expertise in artificial intelligence, who would like to join a dynamic team involved in studying the molecular and cellular mechanisms of ageing.

The candidate should the following skills and experience:

• Master's degree in Cellular or Molecular Biology and/or Computational Biology.
• Past experience in a research laboratory in molecular or cellular biology
• Ideally, a profile with previous internship experience in cardiomyocyte culture maintenance and differentiation of induced pluripotent stem cells (iPSCs) (cell types: cardiomyocytes, fibroblasts, endothelial cells, etc.);
• Programming in R, Python and/or Matlab, data processing;
• Problem solving mindset;
• Motivation for wet-lab experimentation;
• Ability to work in a team;
• Excellent communication skills with diverse audiences are essential;
• Excellent level of English.

All our opportunities are open to people with disabilities

Type of contract:  Doctoral Contract

Starting date: Between September and December 2024

Contract duration: 3 years

Working time: Full time

Remuneration: According to the current grids

Benefits:Collective catering, reimbursement of transportation fees up to 70%, supplementary health insurance

Location: Institut Curie – Paris

Please send your CV, a letter of motivation and the contact (Name, Phone, Email and description of the link with the candidate) for two references to job-ref-zwpacko7ac@emploi.beetween.com

Publication date: 03/07/2024

Deadline for application: 30/09/2024 (until the position is filed)

Institut Curie is an inclusive, equal opportunity employer

and is dedicated to the highest standards of research integrity.

https://euraxess.ec.europa.eu/sites/default/files/brochures/eur_21620_e…