School visits to iMM and ReTuBi labs
On January 17 and on February 8, 2018 two classes of 28 students each, visited iMM namely João Barata and Sérgio Dias labs, Biobank and the Electron Microscopy. The objective of this visit was to explain to students that through the ReTuBi project, the Instituto de Medicina Molecular (iMM) aims to fight cancer by reinforcing its capacity for outstanding pre-clinical and translational research, and by creating a dynamic cluster of excellence within the Lisbon region in the field of cancer research.
ReTuBi School Seminars - "The Biology of Cancer in one hour" (11/2017- 01/2018)
From November 2017 to January 2018, the ReTuBi project promoted several educational sessions entitled "The Biology of Cancer in one hour" addressed to the Secondary School students from the Biology course, in Lisbon. The following sessions were presented by the following researchers:
- Sérgio Dias - Secondary School D. Dinis - November 24, 2017
- Isabel Alcobia, from João Barata Lab - Secondary School of Lumiar - November 27, 2017
- Ana Rita Fragoso, from João Barata Lab - Secondary School Pedro Nunes - January 8, 2018
- Sandrina Nóbrega Pereira, from Sérgio Dias Lab - Secondary School Passos Manuel - January 9, 2018 and Secondary School de Camões - January 16, 2018
The main goal of these educational sessions is to present the iMM Lisboa research in the cancer and tumour biology area. The themes presented were focused on: What is cancer; Cell division; The repair mechanisms of DNA; Types of cancer; Which can lead to cancer; The properties of cancer; The role of the microenvironment and Carcinogenesis and new treatments.
Staff exchange between iMM-Curie (2018/01)
From January 20 to March 4, 2018, Cátia Janota from Edgar Gomes Lab (iMM) made a “ReTuBi Staff Exchange” to Matthieu Piel Lab (Institut Curie). The aim of this staff exchange was to understand how endoplasmic reticulum (ER) morphology impacts on fibroblasts migration and squeezing.
The first phase of the activity was focus on ER morphology during migration and the objective was to understand how is ER organized during cell migration. During the first weeks, Cátia Janota optimized the protocol with NIH 3T3 fibroblasts and measure migration speed on different conditions (control scramble iRNA, silencing of tubules proteins and silencing of sheets proteins).
The second phase of the activity was based on determing if ER plays a role in nuclear deformability and for this purpose, it was used the microchannels that are fabricated at Matthieu Piel’s Lab.
ReTuBi Scholarship Conference Awards 2017
To instigate research excellence and promote international exposure right from the outset of their careers, iMM’s PhD students and post-docs in cancer and tumour biology research field had the opportunity to attend international scientific conferences and with their participation increased the ReTuBi international exposure. To achieve this goal, it was launched three “ReTuBi Scholarship Conference Award” calls during 2017 with fourteen travel grants awarded.
ReTuBi Lecture - Christer Betsholtz
On January 22 of 2018, Christer Betsholtz from Karolinska Institutet (Sweden) was the invited speaker as an expert visit with the lecture “A molecular atlas of the brain vasculature revealed by single cell RNA sequencing”.
Summary of the Lecture:
Angiogenesis – the formation of new blood vessels from pre-existing ones – requires interaction between several cell types and involves signaling molecules, secreted as well as membrane-tethered and their cognate receptors, of many different types. My laboratory focuses on mechanisms of angiogenic sprouting, and the involvement of distinct endothelial phenotypes (tip cells and stalk cells) in this process. We are also investigating the mechanisms leading to the recruitment of vascular mural cells (pericytes and vascular smooth muscle cells) to blood vessels and the role of these cells, in particular the pericytes, in vascular development and function. However, pericyte identification remains challenging due to a paucity of defining markers, and there are not yet any good tools available for their specific genetic manipulation. As a consequence, there is not an accepted consensus about how pericytes should be defined, where they reside, how heterogeneous they are, and what they do. To resolve this problem, we use single cell RNA sequencing to define pericytes and other vascular and vessel-associated cell types of the brain, as well as in other organs. In addition to providing cell type and subtype definitions based on genome–wide quantitative transcriptional information, our data also reveal new insights in the arterio-venous zonation and organotypicity of vascular cell, as well as the identification and definition of hitherto unrecognized vascular cell types.
ReTuBi Lecture - Raphaël Rodriguez
On January 15 of 2018, Raphaël Rodriguez from Institut Curie (France) was the invited speaker as an expert visit with the lecture “An iron hand over cancer stem cells”.
Summary of the Lecture:
Cancer stem cells (CSCs) represent a subset of cells within tumours that exhibit self-renewal properties and the capacity to seed tumours. CSCs are typically refractory to conventional treatments and have been associated to metastasis and relapse. Salinomycin operates as a selective agent against CSCs through mechanisms that remain elusive. We provide evidence that a synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast CSCs in vitro and in vivo, by accumulating and sequestering iron in lysosomes. In response to the ensuing cytoplasmic depletion of iron, cells triggered the degradation of ferritin in lysosomes, leading to further iron loading in this organelle. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis. These findings reveal the prevalence of iron homeostasis in breast CSCs, pointing towards iron and iron-mediated processes as potential targets against these cells.