Staff exchange between iMM-Curie (2017/11)
From November 29 to December 02, Gonçalo Bernardes (iMM) made a “ReTuBi Staff Exchange” to Raphael Rodriguez’s lab in Institut Curie to acquire knowledge in bioorthogonal labelling methods for target identification. This is an important area of chemical biology that addresses and helps identifying new targets for active molecules. This particular expertise from the Rodriguez’s lab fits well with current programs at the Bernardes lab in target id of natural products in cancer. The overall goal of this staff exchange was for Gonçalo to learn how to implement a bioorthogonal labelling approach for target id, establish a new collaboration, and also potentiate new projects. In addition, Gonçalo had the opportunity to present a seminar at the Institut Curie during this staff exchange also allowing to disseminate his group’s research to a larger community.
ReTuBi Event: “Oncology: Talking with Scientists”
On November 8 of 2017, the ReTuBi project in partnership with Instituto de Medicina Molecular João Lobo Antunes and Fundo iMM-Laço promoted the event “Oncology: Talking with Scientists”, specially dedicated to the Portuguese cancer patients associations.
This event had the participation of Luís Costa that presented “Science and cancer patient: an evolving partnership” and of Bruno Silva-Santos that presented “DOT-cells: Towards a new immunotherapy for cancer”. An exhibition of the work of some iMM labs/facilities was also organized to promote iMM research. The labs that participated in this event were: Edgar Gomes, Cláudio Franco, João Barata, Luís Costa and Sérgio Dias. The ZebraFish Facility and the Biobank were also present.
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.