Title of the thesis

Computer Simulation and Experiments of RadioInduced Cell Senescence
SENESIMEX
027

Acronym
Reference number
Hosting institution
Université de Lille
Website: https://www.univ-lille.fr/home/
Hosting research unit 1
Name: Institut d’Electronique Microelectroniqueet Nanotechnologies
Acronym: IEMN
Identification number: UMR 8520
Address: Université de Lille
Campus Cité Scientifique
Avenue Henri Poincaré - CS 60069
59 652 Villeneuve d'Ascq Cedex, France
Website: https://www.iemn.fr/
Principal supervisor
Name: Fabrizio
Surname: CLERI
Email: fabrizio.cleri@univ-lille.fr
Phone: 0320 19 79 28

Employer
CNRS
Website: http://www.dr18.cnrs.fr/
Hosting research unit 2Name: Hétérogénéité, Plasticité et Résistance
aux Thérapies des Cancers
Acronym: CANTHER
Identification number: UMR 9020 CNRS –1277 Inserm
Address: Institut de Biologie de Lille
1 Rue du Professeur Calmette
CS 50447
59021 Lille
Website: www.canther.fr
Co-supervisor
Name: Corinne
Surname: ABBADIE
Email: corinne.abbadie@univ-lille.fr
Phone: 0320 87 11 02

Thesis information
Keywords
Abstract

Ionizing radiations; DNA damage; Cell senescence; Multicellular models; Metabolicand repair pathway simulations
Medical use of radiations for treating cancers and other diseases rests on a vast
amount of empirical knowledge, accumulated over the past century. However,rather little attention is yet paid to the biological specificity of the individual cell
response to ionizing radiation. Computer modelling of DNA damage and repair aims
to give quantifiable depictions of the DNA damage response following therapeutic
irradiation. Notably, a severe complication of radiation therapy is identified in thedevelopment of secondary sarcomas around the irradiated field, a very rare, difficult
to predict, but often lethal pathology. According to a number of experimental
indications, accumulated by our groups and others, it is supposed that normal cells
around the treated primary cancer might be affected by scattered ionizing radiation,
which diffuse in uncontrolled way from the irradiated main volume, and that thepeculiar type of damage accumulated in this way could induce these cells into
senescence; upon exiting from this state at much later times, defects latently
accumulated in some such cells could evolve the secondary sarcoma. We propose todevelop a complete computer model of the cell treatment, starting from thedetailed description of the irradiation source by Monte Carlo dosimetry and microdosimetry; include a multicellular, evolutive description of the irradiated tissue;
radiation damage and repair will be treated in full details at the scale of each single
cell, including competitive pathways for different types of DNA and cell damage;
dedicated high-resolution biology experiments will define ranges of values for fitting
the model parameters, and provide benchmarks to test and improve the computerExpected
profile ofthecandidate
Application
procedure

Net salaryand Lump
Sumsimulations. The candidate PhD student will work at the mathematical andcomputer developments, and take part in the biology experiments, in our twolaboratories of IEMN (UMR8520) and CanTher (UMR9020 CNRS – 1277 Inserm) inLille. Part of the model development will take place in the Cancer Sciences Divisionat the University of Manchester, UK. The resulting computational/experimental
protocol would represent an important step forward into the domain of highprecision, personalized healthcare, by defining a general approach by which thedetailed biological effects of different types of cell damage could be predicted bymathematical modelling.
The successful PhD candidate should have a background in physics, chemistry,mathematical modelling, and a basic knowledge of biophysics; candidates with amore biology-oriented background will be considered, provided they demonstrate asolid competence in applied mathematics. Computer programming skills (Fortran90,C, C++ , Python, MatLab) and fluency in Unix/Linux OS are highly desirable.
The application procedure is detailed on the European programme PEARL website
www.pearl-phd-lille.eu. The funding is managed by the I-SITE ULNE foundation
which is a partnership foundation between the University of Lille, Engineeringschools, research organisms, the Institut Pasteur de Lille and the University hospital.
The application file will have to be submitted before April 15, 2020 (10h Paris Time)and emailed to the following address : international@isite-ulne.fr.
A net salary of about €1,600 + €530 per month to cover mobility, travel and family
costs.