Staff exchange between iMM-Curie (2017/10)

From October 07-14 of 2017, Ana Russo from Cláudio Franco Lab (iMM) made a “ReTuBi Staff Exchange” to Danijela Vignjevic Lab (Institut Curie). Danijela Vignjevic’s lab focuses on cell migration and invasion. They use a combination of molecular and cell biology techniques with live-cell imaging, using gut as a model, to understand how epithelial cells interact with their microenvironment during migration. This staff exchange allowed Ana Russo to learn a new technique that will benefit the research in the area developed by Cláudio Franco’s lab. In this staff exchange Ana Russo observed live imaging techniques in order to implement them in Cláudio Franco’s lab.

ReTuBi Lecture - Ronen Alon

On September 11 of 2017, Ronen Alon, from the Weizmann Institute of Science (Israel) was the invited speaker as an expert visit with the lecture Cues and barriers for immune cell and tumor extravasation .

Summary of the lecture:

Immune cells and subsets of circulating cancer cells exit blood vessels via entirely different pathways. The talk will discuss how the endothelial cytoskeleton is remodeled during leukocyte transendothelial migration (TEM) and how the nuclei of different immune cells allow their rapid squeezing through inflamed endothelial barriers and the interstitial tissue. We find that nuclear squeezing and transmigration of leukocytes and metastatic tumor cells are mediated by different actomyosin driven mechanisms of polarity and motility. Correlative electron microscopic analysis of transmigrating T cells suggest that their nuclei displace the different endothelial actin filaments that serve as barriers for their squeezing through either the endothelial junctions or via transcellular pores. We suggest that the leukocyte nuclei, in contrast to tumor cell nuclei, are mechanically adapted to promote rapid leukocyte squeezing and TEM activity through the dense endothelial cytoskeleton and the interstitial collagenous space. Our recent findings link these exceptional properties of leukocyte nuclei to a low expression of the nuclear laminar protein lamin A.

Staff exchange between iMM-DKFZ (2017/08)

From August 14-28 of 2017, Mariana Sequeira from Luísa Figueiredo Lab (iMM) made a “ReTuBi Staff Exchange” to Erec Stebbins Lab (DKFZ) to improve her general knowledge on protein biochemistry and diversification, to be exposed to state of the art instruments for mass-spectrometry and protein analysis and to learn about new bioinformatic tools to study large proteome data sets obtained by mass-spectrometry. This Staff Exchange was very helpful for Mariana’s training in proteomic analysis.

ReTuBi Lecture - Benilton Carvalho

On July 24 of 2017, Benilton Carvalho, from University of Campinas (Brazil) was the invited speaker as an expert visit for the lecture "Brazilian Initiative on Precision Medicine: Statistical Perspectives”.

Summary of the lecture:

Significant efforts are being made in favor of the development of Genomic Medicine (GM). In this framework, clinicians use molecular profiles to guide the delivery of treatments to their patients. Such profiles are built using data generated from Next-Generation Sequencing and other high-throughput experiments, like DNA-Seq, RNA-Seq, ChIP-Seq, high-density microarrays and mass spectrometry. Building these profiles requires a series of complex statistical procedures that should be capable of handling terabytes of data in an efficient manner. In addition to that, it is essential that the medical doctors have access to a comprehensive molecular profile of the reference population. This will allow the proper identification of molecular patterns that are not found on the healthy population and may become candidates for causal variants. I will discuss the strategies used by the Brazilian Initiative on Precision Medicine (BIPMed) to bring to the public information and methods on the genomic complexity of the Brazilian population. BIPMed is the first initiative of its kind in Latin America and has been recognized by the international community for its pioneering efforts on Precision Medicine. I will present the solutions proposed by BIPMed to provide and analyze genomic data under the medical context, including protocols for data distribution and statistical approaches implemented in our software, which is distributed freely by Bioconductor. I will present information on the molecular characterization on Brazilian subjects, discuss the importance of national initiatives of Genomic Medicine and present our latest findings in the field, showing the potential of associating Statistics and Medicine, resulting in significant changes on the current medical practice.


Staff exchange between iMM-Curie (2017/07)

From July 5-9 of 2017, Simão Teixeira da Rocha from Maria do Carmo Fonseca Lab (iMM) made a “ReTuBi Staff Exchange” to Edith Heard Lab (Institut Curie) to finalize a manuscript in collaboration in order to submit it in a high impact journal. 

From July 7-23 of 2017, Francisca Vasconcelos from Cláudio Franco Lab (iMM) made a “ReTuBi Staff Exchange” to Franck Perez Lab (Institut Curie) to improve new technical skills on vesicle intracellular trafficking and molecular system for controlled secretion of cargo proteins and a high-throughput screening for automated analysis. 

ReTuBi Lecture - João Matos

On July 3 of 2017, João Matos, from ETH Zürich (Switzerland) was the invited speaker as an expert visit for the lecture “Transcriptional and metabolic regulation of vascular form and function”.

Summary of the lecture:

To prevent the catastrophic segregation of incompletely replicated chromosomes, eukaryotic cells target stalled replication intermediates for nucleolytic resolution in mitosis. The MUS81 endonuclease plays a pivotal role in this process, but whether and how cells prevent it from cleaving related DNA structures arising during unperturbed S-phase was unclear. In recent work we showed that MUS81 is active throughout the cell cycle, but requires association to the SLX4 scaffold for efficient substrate targeting. To preclude toxic processing of vital replication intermediates, WEE1 kinase restrains CDK1-mediated MUS81-SLX4 assembly during S-phase. Accordingly, WEE1 prevents widespread recruitment of MUS81-SLX4 to S-phase chromosomes and WEE1 inhibition elicits extensive cleavage of replication intermediates, triggering chromosome pulverization. Our work suggests that temporally restricted MUS81-SLX4 association suppresses toxic breakage of replication intermediates, while promoting resolution of under-replicated DNAs that would otherwise impair chromosome segregation.  We have recently published these findings (Duda et al., 2016) but are continuing this project with two complementary research lines. On the one hand, we are investigating the mechanism by which CDK1 promotes MUS81-SLX4 association. On the other hand, we are exploring the phenomenon of chromosome pulverization, which was described more than 40 years ago by Johnson and Rao in pioneering cell-cell fusion experiments. Importantly, this phenomenon has recently regained attention since it has been implicated in chromothripsis. Because of its M-phase-specific ability to process replication intermediates, we are investigating whether MUS81-SLX4 might be the elusive mitotic factor that pulverizes replicating chromosomes in cell-cell fusion experiments. I will discuss our progress in both projects.