Characterization of immunogenic cytosolic DNA species induced by DNA replication stress (RS).
PhD position in molecular biology in the group of Dr Philippe Pasero at the Institute of Human Genetics (IGH, CNRS and University of Montpellier, France).
What is the candidate going to do?
Pioneering work from our laboratory has shown that DNA fragments released from stressed replication forks accumulate in the cytosol and induces inflammation (Coquel, Nature 2018). However, the nature of these fragments has remained elusive because of the lack of appropriate assays to analyze them. We have recently implemented a novel microfluidic approach to purify, concentrate and characterize cytosolic DNA fragments formed under different genotoxic stress conditions. During your PhD, you will exploit this technology with the help of a biophysicist to decipher how small DNA fragments are excised from the genome, released into the nucleoplasm, transported into the cytosol, detected by innate immunity sensors and degraded by cytosolic nucleases or secreted via extracellular vesicles. These studies will generate invaluable information on the fascinating interplay between replication stress and inflammation. You will also use this information to design new strategies to stimulate antitumoral immunity in preclinical studies using immunocompetent mouse models. These studies will be performed under various replication stress conditions, including altered licensing (Lygerou, UP) and ISG15 upregulation (Penengo, UZH), with the help of Adelis, the biotech who developed and distributes the fluidic system used in the project.
What does the candidate have to offer?
MSc in Molecular Biology and/or Biochemistry
High motivation and passion for research
Autonomous and well-structured working style
Good organizational and communication skills
Excellent spoken and written English, French is a plus
The IGH is a CNRS research institute affiliated to the University of Montpellier, one of the largest universities in France (50000 students). The IGH presently houses 22 research groups distributed in three scientific departments (Genome Dynamics, Genetics and Development, Molecular Bases of Human Diseases). Research performed at the IGH aims at understanding fundamental biological processes related to the function of our genome and at deciphering the molecular and cellular mechanisms at the origin of human pathologies, with a particular interest for cancer and AIDS. IGH personnel composition is very international, with more than 20 different countries of all continents present today. Over 50% of PIs, postdocs and PhD students are of foreign origin.
Do you have any questions or do you require additional information? Please contact: Dr Philippe Pasero; email@example.com, +33 620 06 17 66.
Funded by the European Union under grant agreement N.101046314. Views and opinions are those of the author(s) only and do not necessarily reflect those of the European Union.