Stage M2: Regulation of the suppressive function of myeloid cells by long noncoding RNAs in cancer.

We are looking for a highly motivated M2 student willing to explore how lncRNAs regulate the acquisition of functions and cell differentiation process using temporal transcriptomic data.

Scientific background

The acquisition of suppressive function in monocyte populations plays a key role in cancer progression and resistance to immunotherapies, through inhibiting T cell functions. Single-cell transcriptomics has allowed a better characterization of these suppressive cells, especially in liver cancer [1]. Their characterization is mainly based on the expression of protein coding genes. However, in any cell type, 2/3 of the genome is transcribed and only 2% of this genome consists of protein coding transcripts. Therefore, the vast majority of our genome is composed of non-coding genetic sequences. Among them, microRNAs and lncRNAs are the two most studied classes in cancer.
By interacting with DNA, mRNAs, miRNAs and proteins, lncRNAs are considered major regulators of gene expression, influencing core processes such as chromatin remodeling, transcription, splicing, RNA degradation and translation. Furthermore, their tissue- and cell-specific expression patterns suggest that they are key regulators of cell fate. HOTAIRM1 is the first discovered lncRNA involved in myelopoiesis and regulation of suppressive activity. However, very few studies have focused on the temporal and dynamic patterns of activity throughout the process of differentiation and function acquisition.

Objectives

The general objective of the internship is to study the regulation of suppressive functions by lncRNAs in the tumor microenvironment through NGS data analyses. The student will work on a temporal transcriptomic (RNA-seq) dataset (several time points during differentiation), produced from monocyte cultures, by our collaborators in the immunology laboratory. The main objectives are to identify both the lncRNAs temporally expressed during the differentiation of suppressor monocytes, and the genes co-expressed with the lncRNAs. The student will first use annotations of the human genome (via GENCODE) which contains more than 30,000 lncRNAs. In a second step, k-mers methods will be used to identify potentially new lncRNAs that are not yet annotated and are specifically involved in the regulation of suppressive function. Thus, analyses of both already annotated lncRNAs as well as newly identified by k-mers will be performed.

Skills

We are looking for either a biology student with a strong interest in data analysis and bioinformatics, or a bioinformatics student with a specialization in data analysis. The following skills are assets:

• Knowledge of omics concepts and terminologies (transcriptomics, genomics)
• Knowledge of biological and statistical analysis of high-throughput data
• Use of at least one programming and/or analysis language (Python, R, ...)
• Mastery of the Unix/Linux environment and the Bash language
• Knowledge of basic molecular/cellular biology and immunology

Environment

The internship will take place at the IBGC under the supervision of Domitille Chalopin-Fillot and Macha Nikolski.

Contacts: Domitille Chalopin (domitille.chalopin-fillot@u-bordeaux.fr) and Macha Nikolski (IBGC team leader and CBiB director, macha.nikolski@u-bordeaux.fr).

Duration of the internship: 6 months

Amount of compensation: statutory internship compensation. The gratification will be provided by a grant from the Bordeaux network NEWMOON.

Reference

[1] Giraud*, Chalopin* et al. TREM1+ regulatory myeloid cells expand in steatohepatitis-HCC and associate with poor prognosis and therapeutic resistance to immune checkpoint blockade. bioRxiv, https://doi.org/10.1101/2022.11.09.515839.