<p><span style="color: rgb(34, 34, 34); font-family: arial, sans-serif; font-size: 13px; background-color: rgb(255, 255, 255);">34094 cedex 5, 141 Rue de la Cardonille, 34090 Montpellier</span></p>
Intron retention (IR) occurs when an intron is included in a mature mRNA. Previously regarded as a byproduct of faulty splicing, transcripts with retained introns are often rapidly degraded by a surveillance mechanism called nonsense-mediated decay (NMD). Our team discovered that numerous cell types make use of this mechanism by increasing the amount of transcripts with retained introns for degradation in blood cells (Cell, 2013) and in pluripotent stem cells (Nature, 2014). IR was also recently found to modulate tumour suppressor genes in many different cancers (Nature Genetics, 2015). However, because IR could not previously be correctly identified, numerous studies have overlooked potential biomarkers and therapeutic targets linked to this novel type of gene regulation.
In this thesis proposal, we will use a new sequencing technology (oxford nanopore) to investigate intron retention with unprecedented accuracy. We will use third generation ultra-long sequencing technology to study the role of IR during the epithelial-to-mesenchymal transition (EMT) that confers invasive and stem cell properties to tumour cells, which turn them highly metastatic and resistant to chemotherapy. This will require the use of novel bioinformatics methods to combine long reads that have high error rates with small sequencing that are more precise. The student will learn to master bioinformatics analysis of multiple types of sequencing technologies and use advanced statistics to discover how intron retention is regulated and how it affects gene expression.
The student will integrate and be supervised by a team with extensive bioinformatics experience and a strong track record in RNA regulation. The student will also be in contact with multiple wet lab groups who are world leaders in coding and non-coding RNA regulation.