ReTuBi Lecture - Andreas Fischer
On October 24 of 2017, Andreas Fischer from DKFZ (Germany) was the invited speaker as an expert visit with the lecture “Notch signaling in vasculature: angiogenesis and beyond”.
Summary of the Lecture:
Abnormal blood vessel growth and vessel function is a hallmark of cancer. Notch signaling is a central coordinator of angiogenesis. We have developed novel Notch inhibitory and stimulatory peptides to manipulate sprouting angiogenesis and identified novel Notch ligand-interacting proteins. Their manipulation alters the tumor vasculature and interferes with tumor growth. In addition we could show that endothelial Notch signaling is frequently hyperactive in the tumor vasculature and that this promotes several steps of the metastatic cascade. Mechanistically, sustained Notch1 activity led to endothelial cell senescence, expression of chemokines, adhesion factors and weakening of cellular junctions. This promotes infiltration of primary tumors with granulocytic myeloid-derived suppressor cells, facilitates tumor cell intravasation and survival at distant sites. Lastly, we will give some insight how Notch signaling in the blood vessel wall controls the flux of nutrients from plasma to muscle cells and how this affects systemic metabolism.
ReTuBi Lecture - Guillaume Montagnac
On October 23 of 2017, Guillaume Montagnac from the Gustave Roussy Institute (France) was the invited speaker as an expert visit with the lecture “Frustrated endocytosis in cell migration and mechanotransduction”.
Summary of the Lecture:
Endocytosis is a fundamental process that allows the cell to feed itself, to control the composition of its plasma membrane, but also to regulate signaling pathways, for example by "shutting down" signaling from receptors activated at the cell surface. Endocytosis therefore allows the cell to adjust to its environment and to provide an adapted response to the different signals it encounters. To be effective, we assume that the dialogue between extracellular medium and endocytosis must be bi-directional. In the laboratory, we study how the physical properties of the cell environment affect clathrin-dependent endocytosis. Our work shows, for example, that the topology or the rigidity of the cellular environment have profound consequences on endocytosis, in particular mechanically preventing the proper formation of endocytosis vesicles. We investigate how this frustrated endocytosis, far from trivial, affects the ability of cells to migrate into complex environments and to proliferate.
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.
From October 18-21 of 2017, Cátia Janota from Edgar Gomes Lab (iMM) made a “ReTuBi Staff Exchange” to Matthieu Piel’s lab. Matthieu Piel’s lab is a world leader in cell polarization, a process which involves a reorganization of the cell cytoskeleton and movement of cellular organelles. This is usually an event triggered by external cues. In Matthieu Piel’s lab a lot of innovative tools bason on micro-fabrication techniques, like microchannels, coupled to quantitative microscopy. These microchannels allow scientists to control the main physical and chemical parameters of the cell micro-environment. Trough this Staff Exchange, Edgar Gomes’s Lab, increased its expertise in nuclear movement, by allowing Cátia Janota to learn and develop a new technique in Edgar Gomes’s lab.
From October 30-31 of 2017, Ana Filipa Almeida (iMM Career Development Unit), Afonso Duarte (iMM Funding Office), Liliana Bento (ReTuBi Project Manager) and Sofia Santos (iMM Human Resources) made a “ReTuBi Staff Exchange” to the Institut Curie to exchange knowledge and expertise in the following departments: Training Unit; Human Resources; Funding Office and Tech Transfer Unit. With this Staff Exchange the iMM Staff could get an overview about the several departments of Institut Curie, the overall organization of Institut Curie, the ongoing activities/initiatives, the funding programmes and the assessment of the outcomes of the several activities”.
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.