Nuclear and mitochondria instability in health and cancer Scientific Symposium

From July 3 to 5, 2018 it was held the "Nuclear and mitochondria instability in health and cancer Scientific Symposium", in Montargil, Portugal. This ReTuBi event had a total of 31 participants from Instituto de Medicina Molecular, Institut Curie and from the Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER).

ReTuBi Lecture - Antonin Morillon

On July 2 of 2018, Antonin Morillon from Institut Curie (France) was the invited speaker as an expert visit with the lecture “The dark side of the genome: pervasive they said”. 

Summary of the Lecture:

Among the signals that control the epigenetic landscape, non-coding (nc)RNAs have been identified to play a major role but the generalization and the mechanisms of their activity are still poorly apprehended. Recent data using high-throughput technologies have profoundly changed our view on how the genomes are organized. Indeed transcriptome analyses have shown that large genomic regions are pervasively transcribed producing a broad variety of lncRNA which functions on the epigenome remain to be deciphered. Recent works showed that S. cerevisiae’s genome also supports production of non-coding protein large transcripts, which are strongly controlled by RNA decay pathways. Of specific interest are the lncRNA XUT that we described recently, mostly antisense to class II genes and associated with a consistent regulatory potential through epigenetic modifications. Here, I will present data providing insights on their regulatory activity which is conserved also in S. pombe containing RNAi pathway. The transcription and post-transcription-mediated regulatory activities of antisense transcripts will also be discussed in human cells where we draw an unprecedented landscape of antisense transcription in cancer cell lines and tumors.

ReTuBi Lecture - Ingrid Grummt

On June 18 of 2018, Ingrid Grummt from DKFZ (Germany) was the invited speaker as an expert visit with the lecture DNA:RNA triplexes – a liaison between regulatory RNAs and chromatin”.

Summary of the Lecture:

Nuclear long non-coding RNAs (lncRNAs) have been implicated on most, if not all, chromatin-mediated processes. While cataloging the transcriptional output of sequenced genomes has led to new approaches for the discovery of thousands of bona fide lncRNAs, few of these lncRNAs have been ascribed function and very little is known about their mode of action and regulation. We have discovered a novel long non-coding RNA (lncRNA), Khps1, which is transcribed in antisense orientation to the proto-oncogene SPHK1. Khps1 interacts with a homopurine stretch upstream of the transcription start site of SPHK1, forming a DNA:RNA triplex that tethers Khps1 to SPHK1 and guides Khps1-associated p300/CBP to the SPHK1 promoter to local changes of the chromatin structure that activates SPHK1 transcription. Deletion or mutation of the triplex-forming region diminishes enhancer occupancy of E2F1 and p300, attenuates KHPS1-dependent activation of SPHK1 transcription and impairs cell migration and proliferation. 

To examine whether lncRNA-mediated triplex formation is a general mechanism of epigenetic regulation, we have established a genome-wide method that allows genome-wide mapping of RNAs that are engaged in DNA:RNA triplex structures. High-throughput sequencing and computational analysis revealed a large set of triplex-forming RNAs originating from non-coding and coding loci harboring super-enhancer and repeat sequences. In a complementary approach, we have identified DNA sequences that are engaged in DNA:RNA triplex structures. Analysis of DNA-associated RNA regions combined with identification of genomic loci that are targeted by triplex-forming RNAs reveals that DNA:RNA triplex formation is a general mechanism of RNA-mediated target-site recognition.  

Joint Lab Retreat on Trafficking and Cell Migration in Cancer

From June 6 to 8, 2018 it was held the Joint Lab Retreat on "Trafficking and Cell Migration in Cancer", in Sintra, Portugal. This ReTuBi event had a total of 30 participants from Instituto de Medicina Molecular, Institut Curie and IFOM, the FIRC Institute for Molecular Oncology! Great opportunity to discuss outstanding science!

Cell Migration under confinement Workshop 2018

From May 02 to 04 in Douro (Portugal) it was held the Cell Migration under confinement Workshop 2018 with a total of 41 participants from Instituto de Medicina Molecular - João Lobo Antunes (iMM), Institut Curie, DKFZ, The Francis Crick Institute and University College London.


ReTuBi Lecture - Kristine Schauer

On April 26 of 2018, Kristine Schauer from Institut Curie (France) was the invited speaker as an expert visit with the lecture “Role of actin - and microtubule - dependent motor proteins in Golgi positioning and trafficking”.

Summary of the Lecture:

Many cellular disorders are accompanied by changes in the morphology and positioning of intracellular organelles, yet the functional consequences of organelle alterations are often not clear. The Golgi apparatus is a large and distinctive organelle in mammalian cells constituting the biggest hub of intracellular trafficking at the interface between anterograde and retrograde routes. Although the Golgi apparatus was one of the first organelles to be discovered and observed in detail, the function of its compact structure remains enigmatic. We study cells on bioengineered surfaces of micro-fabricated patterns that provide adhesive cues for defined cell spreading. This approach reduces cell-to-cell variation and mimics space restriction which cells encounter in tissues. We combine this controlled cell culture condition with precise quantification of organelle positioning using a density-based imaging approach. We have previously shown that the Golgi apparatus has a characteristic, well-defined, stable and reproducible organization in micropatterned cells. Because morphology and spatial positioning of organelles are regulated by the cytoskeleton and molecular motor proteins, we are interested in the role of motors at the Golgi. We have used our density-based approach on micropatterns to screen for actin-dependent myosins and microtubule-based kinesins that alter the morphology of the Golgi apparatus. We have identified Myo1C and Kif5B as critical players and have further characterized their role in Golgi positioning, trafficking and cell function. Our analysis will be helpful to understanding the molecular mechanisms underlying intracellular changes associated with cellular pathogenesis such as cancer.