B cell repertoire evolution as a fnction of age
Supervisors
Aleksandra Walczak
CNRS,1st supervisor
Dario Riccardo Valenzano
FLI, 2nd supervisor
Objectives
The goal of the PhD project is to develop new computational methods and mathematical models to understand how the B cell repertoire changes with age. The adaptive immune system’s B cell repertoire changes significantly with age, influenced by factors such as microbiome composition and diet. Understanding these dynamics can provide insights into immune ageing and enhance our ability to predict immune responses. This project aims to analyse B cell repertoire evolution, using killifish and mice across different life stages as model systems, leveraging computational methods to explore the role of age and environmental factors on immune diversity. Specific objectives:
Develop computational methods to model selection in B cell repertoires, addressing complexities of somatic evolution.
Characterize age-related shifts in B cell repertoire diversity in killifish, identifying key sequence features.
Examine coevolution between the microbiome and B cells, focusing on age-related interactions.
Methodology
The PhD student will develop specialised statistical and computational methods to tackle the questions. These will be based on a mixture of statistical inference, machine learning and population genetics
Required Skills
Background in physics, applied mathematics, statistics or similar fields. Both analytical and numerical skills required. The student will work on both data analysis and method development and a need to integrate mathematical models with inference approaches is needed.
Expected Results
The project will produce new computational tools for B cell repertoire analysis, uncover age-dependent changes in B cell diversity, and identify coevolving microbial species. These insights will form the basis for models of immune dynamics that predict age-related immune responses.
Planned Secondments
FLI (Valenzano) in year 2 (2 months) to train on killifish research and establish collaborations with DC1.
UCAM (Blundell) in year 3 (1 month) to learn the protocols about B cell sequencing and analysis.
GIMM (Gordo) in year 2 (2 weeks) to develop models of host-microbiome interactions, extending the analysis to
include innate immunity.
Microomics in year 3 (1 week) to learn about highthroughput microbiome quantification methods.
Enrolment in doctoral programs
The student will be enrolled in the Ecole Doctorale d’Ile de France (EDPIF) doctoral school and receive a degree from the École Normale Supérieure — Paris Sciences Lettres University.