Section: Partnerships and Cooperations

International Initiatives

Inria Associate Teams

Modeling leukemia
  • Title: Modeling quiescence and drug resistance in Chronic Myeloid Leukemia

  • Inria principal investigator: Thomas Lepoutre

  • International Partner (Institution - Laboratory - Researcher):

    • University of Maryland (United States), Center for Scientific Computation and Mathematical Modeling.

  • Leukemia is the most famous disease of the blood cell formation process (hematopoiesis). Chronic myeloid leukemia results in a uncontrolled proliferation of abnormal blood cells. As the hematopoiesis involves stem cells (not accessible to observations), mathematical modeling is here a great tool to test hypothesis. We will join the expertise of Inria team DRACULA specialized on the modeling of blood cell formation and the Center for Scientific Computation and Applied Mathematical Modeling (CSCAMM, University of Maryland, College Park). The theoretical and modeling experience of team DRACULA and the numerical expertise combined with the links with experimentalists of members of CSCAMM will allow us to study deeply evolution of leukemia. We will especially focus on the behavior of leukemic stem cells and their possibility of becoming quiescent (dormant). Then we will study (using the knowledge obtained on leukemic stem cells) the phenomenon of drug resistance and its propagation over time and finally the mechanisms of multidrug resistance.

Participation In other International Programs

  • Program: Euromediterranean 3+3

  • Title: Mathematical Models and Methods in Cell Dynamics

  • Inria principal investigator: Mostafa Adimy

  • International Partners (Institution - Laboratory - Researcher):

    • Institut Pasteur de Tunis (Tunisia) - Slimane Ben Miled

    • Consiglio Nazionale delle Ricerche- Istituto per le Applicazioni del Calcolo Mauro Picone (Italy) - Istituto per le Applicazioni del Calcolo Mauro Picone - Roberto Natalini

    • Cadi Ayyad University (Morocco) - Populations Dynamics Laboratory - Moulay Lhassan Hbid

  • Duration: Jan 2012 - Dec 2015

  • The aim of this project is to establish a network working on mathematical and computational models in cell dynamics. This network consists of five groups which have already established close bilateral relations. Those are the Inria teams Bang and Dracula in Paris and Lyon, France, the team IAC-CNR in Rome, Italy, the laboratory of Mathematical Population Dynamics (LMDP) from the university of Marrakech in Morocco, and the team of Mathematical Modelling and Computing in Biology (MoMinBi) from the Pasteur Institute in Tunis. Modelling cell dynamics and related processes is one of the main subjects of interest for the partners for many years. The issues addressed in the present project can be divided into five parts:

    1) Analysis of structured models in cell population dynamics ;

    2) Dynamics of normal and pathological haematopoiesis ;

    3) Dynamics of Darwinian adaptation, in particular by drug resistance in competing cell or parasite populations, healthy and pathological / pathogenic (cancer, bacteria, parasites) ;

    4) Dynamics of chemical and physical determinants of filament formation and intracellular spatial organisation of the cytoskeleton conformation ;

    5) Coupling of the molecular mechanisms of control of the cell division cycle and cell proliferation.

    The first part has been developed for many years by all the partners in this project. It tackles issues related to cell dynamics and biological mechanisms, physiological and chemical properties of cells and cell populations. The other four aspects of the project have been studied in the past by the Inria teams "Bang" and "Dracula" (2, 4, 5) and the IAC-CNR team (Rome), or are a rapidly emergent theme in Bang (3, cell Darwinism) with possible and natural connections with the other teams, in particular IAC-CNR and MoMinBi in Tunisia. Themes (2, 4, 5) have also been initiated (for their fundamental part) in a recent collaboration between Dracula and the teams from Morocco and Tunisia. The objectives of the present project are to pursue and deepen the study of cell proliferation dynamics and cellular mechanisms using structured models that take into account some new structure variables. The development of computer models will also be investigated in this project. Training and research activities related to these topics are currently underway between the Inria teams and the teams from Marrakech and Tunis, and between the Italian team and Bang. Two co-supervised theses are currently in progress, a Spring school on this subject will be organised by the partners in 2012. This program comes at the right time to give a new impetus to this collaboration. It will lead to the establishment of a multi-site laboratory expertise in population dynamics modelling, especially in cellular dynamics. This project will also allow the teams from Morocco and Tunisia to use their knowledge on mathematics applied to cell dynamics.