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PhD student position on 3D genome organization upon oncogenic virus infection

PhD student position on 3D genome organization upon oncogenic virus infection

An ANR funded PhD position (3 years) is available in the team Regulation of Genome Architecture and Dynamics of Splicing
(ReGArDS) at the LBMC (Laboratory of Biology and Modeling of Cell, ENS-Lyon, France) on the role of 3D genome
conformation in the coordination of transcription and alternative splicing events upon virus-induced oncogenesis.
The human retrovirus HTLV-1 is the etiologic agent of various inflammatory diseases and of an aggressive CD4+ T-cell
malignancy called Adult T-cell Leukemia/Lymphoma (ATLL) (1). The infection of CD4+ T-cells by HTLV-1 induces constitutive
activation of NF-kB transcription factors promoting gene deregulation that contributes to the clonal expansion of infected
cells, viral persistence, and HTLV-1-associated pathogenesis. We have recently evidenced that, besides transcription, NF-
kB activation by the viral oncoprotein TAX affects alternative splicing, which is a transcription-coupled process considered
as a major actor in transcriptome/proteome diversity and cell phenotype (2). Through an integrative analysis of 3D
chromatin topology (HiC, 4C, and 3C) and gene expression profiles, our unpublished data indicate that transcription and
splicing events induced by TAX result from 3D genome changes involving differential gene-gene contacts, indicating that
alternative splicing does not solely rely on local genomic and epigenetic features of the target exon, but also that it depends
on its dynamic nuclear localization with other transcriptionally coregulated genes. These results reveal a new layer of gene
regulation triggered by the viral oncogene and NF-kB activation, which needs to be further investigated to improve our
knowledge of HTLV-1-induced leukemogenesis.

The candidate will decipher the mechanisms underlying transcription and alternative splicing regulation upon 3D genome
motion in the context of HTLV-1 infection. To this end, we will carry out integrative analyses of gene expression, epigenetic
regulation, 3D genome organisation of HTLV-1 infected cells using various methods of molecular and cellular biology such
as chromosome conformation capture (4C & 3C), RNA-seq & Nanopore Long-read sequencing technology, Chip-seq and
Cut&Run-seq, and smiFISH. This project will be conducted in close collaboration with our ANR partner Reini Luco in the
Genome Integrity, RNA and Cancer Lab at Curie Institute (UMR3348).

Applicant profile

The applicant must hold or be preparing a master degree in molecular biology or related field. An experience in cell culture,
classical molecular biology techniques, and bioinformatic skills will be appreciated. The candidate should be highly
motivated, rigorous, able to conduct independent research. He/She will be part of the ReGArDS team working on the
interface between 3D genome and splicing regulation at molecular level and so must be willing to interact with his/her
colleagues and also with other LBMC teams working on the 3D genome.

Information and application

Please contact Franck Mortreux (franck.mortreux[ at ] Deadline for application: Sept 15th, 2022.

1. Harhaj, E. W., and Giam, C. Z. (2018) NF-kappaB signaling mechanisms in HTLV-1-induced adult T-cell
leukemia/lymphoma. FEBS J
2. Ameur, L. B., Marie, P., Thenoz, M., Giraud, G., Combe, E., Claude, J. B., Lemaire, S., Fontrodona, N., Polveche, H.,
Bastien, M., Gessain, A., Wattel, E., Bourgeois, C. F., Auboeuf, D., and Mortreux, F. (2020) Intragenic recruitment of NF-
kappaB drives splicing modifications upon activation by the oncogene Tax of HTLV-1. Nat Commun 11, 3045