Early spring publications of the CMMI: congratulations to our collaborators!

Conformation-dependent partitioning of yeast nutrient transporters into starvation-protective membrane domains.
Gournas C, Gkionis S, Carquin M, Twyffels L, Tyteca D, André B.
Proc Natl Acad Sci U S A. 2018 Mar 20. pii: 201719462. doi: 10.1073/pnas.1719462115

The plasma membrane of eukaryotic cells is compartmentalized into domains enriched in specific lipids and proteins. However, our understanding of the mechanisms and functions of this lateral segregation remains incomplete. In this study led by Christos Gournas from the Molecular Physiology of the Cell lab (ULB), we report that the clustering of the yeast Can1 arginine transporter into domains is dictated by its conformation and requires sustained biogenesis of complex sphingolipids. Furthermore, this clustering confers to Can1 and other transporters protection from ubiquit-independent endocytosis. Under nutrient starvation conditions, this protective role is reinforced, thereby allowing cells to preserve a fraction of their nutrient transporters from bulk endocytosis and to more efficiently resume growth when replenishing compounds are available. Our study reveals nutrient-regulated protection from endocytosis as an important role for protein partitioning into membrane domains.02The images above were acquired on the CMMI’s Zeiss LSM710, using its Airy Scan module. Shown are surface section of an art1Δ bul1/2Δ gap1Δ can1Δ PIL1-mCherry yeast strain expressing Can1-GFP, Can1(T180R)-GFP, or Can1(S176N,T456S)-GFP. Can1(T180R) is a loss-of-function mutant of Can1 that is unable to bind Arg. Can1(S176N,T456S) is a mutant converted into a Lys-scpecific transporter. Taken together with additional data in the article, these observations demonstrated that substrate transport abolishes Can1 EMC clustering. Conditions and quantifications (n = 32–42) are as in B. ***P < 0.001; ns, nonsignificant, P > 0.05. (Scale bar: 2 μm.).

New Folate-Grafted Chitosan Derivative To Improve Delivery of Paclitaxel-Loaded Solid Lipid Nanoparticles for Lung Tumor Therapy by Inhalation.
Rosière R, Van Woensel M, Gelbcke M, Mathieu V, Hecq J, Mathivet T, Vermeersch M, Van Antwerpen P, Amighi K, Wauthoz N.
Mol Pharm. 2018 Mar 5;15(3):899-910. doi: 10.1021/acs.molpharmaceut.7b00846. Epub 2018 Jan 30

Inhaled chemotherapy for the treatment of lung tumors requires that drug delivery systems improve selectivity
for cancer cells and tumor penetration and allow sufficient lung residence. The study led by Rémi Rosière from the Laboratoire de Pharmacie Galénique et Biopharmacie demonstrates the positive impact of using coated “solid lipid nanoparticles” on the delivery of paclitaxel by inhalation.03The CMMI’s contribution to the study was to image solid lipid nanoparticles by transmission electron microscopy. The figure above compares the morphology of paclitaxel-loaded solid lipid nanoparticles with or without F-PEG-HTCC coating. Scale bar: 200 nm.

A prospective clinical study of the implications of IL-8 in the diagnosis, aggressiveness and prognosis of prostate cancer.
Roumeguère T, Legrand F, Rassy EE, Kaitouni MI, Albisinni S, Rousseau A, Vanhaeverbeek M, Rorive S, Decaestecker C, Debeir O, Boudjeltia KZ, Aoun F.
Future Sci OA. 2017 Nov 15;4(2):FSO266. doi: 10.4155/fsoa-2017-0084. eCollection 2018 Feb.

In this collaborative clinical study, researchers from three hospitals (Erasme hospital in Brussels, André Vésale Hospital in Charleroi and Hôtel Dieu de France Hospital in Beirut) as well as from the CMMI investigate the relationship between the IL-8 cytokine and prostate cancer. They conclude that IL-8 serum level is not a significant predictor of diagnosis, aggressiveness or prognosis of prostate cancer.

With a little delay, here are some of the winter publications of the CMMI…

Murine stroma adopts a human-like metabolic phenotype in the PDX model of colorectal cancer and liver metastases.
Blomme A, Van Simaeys G, Doumont G, Costanza B, Bellier J, Otaka Y, Sherer F, Lovinfosse P, Boutry S, Palacios AP, De Pauw E, Hirano T, Yokobori T, Hustinx R, Bellahcène A, Delvenne P, Detry O, Goldman S, Nishiyama M, Castronovo V, Turtoi A.
Oncogene. 2018 Mar;37(9):1237-1250. doi: 10.1038/s41388-017-0018-x. Epub 2017 Dec 15.

Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine counterpart. The present study investigates this issue in PDX models of colorectal cancer and liver metastasis, with an approach combining metabolomics (MALDI imaging) and the measurement of glucose uptake by in vivo PET. The data show for the first time that CRC/CRC-LM PDX model maintains the functional stability at the metabolic level despite the early replacement of the human stroma by murine cells. The findings demonstrate that human cancer cells actively educate murine stromal cells during PDX development to adopt the human-like phenotype.

01The inner-rod component of Shigella flexneri type 3 secretion system, MxiI, is involved in the transmission of the secretion activation signal by its interaction with MxiC.
El Hajjami N, Moussa S, Houssa J, Monteyne D, Perez-Morga D, Botteaux A.
Microbiologyopen. 2018 Feb;7(1). doi: 10.1002/mbo3.520. Epub 2017 Dec 1.

Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.
Salade L, Wauthoz N, Deleu M, Vermeersch M, De Vriese C, Amighi K, Goole J.
Int J Nanomedicine. 2017 Nov 28;12:8531-8543. doi: 10.2147/IJN.S147650. eCollection 2017.

A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells.
Balhuizen A, Massa S, Mathijs I, Turatsinze JV, De Vos J, Demine S, Xavier C, Villate O, Millard I, Egrise D, Capito C, Scharfmann R, In’t Veld P, Marchetti P, Muyldermans S, Goldman S, Lahoutte T, Bouwens L, Eizirik DL, Devoogdt N.
Sci Rep. 2017 Nov 9;7(1):15130. doi: 10.1038/s41598-017-15417-2.

Big success for our “CMMI meets industry” event on March 19, with about 90 participants. We are very happy with the positive feedback. Thanks to Biowin, the TTO, the AVRE, our sponsors Zeiss, Bruker and BioSPX, and congratulations to the entire CMMI team for their contributions !


The CMMI will give a seminar to present its activities at the IRIBHM on April 12, at 13:00. You are working on the Erasme campus? Come and meet us !

The CMMI is happy to announce the publication of a study led by our colleagues of the Molecular Physiology of the Cell lab of the ULB.
Congratulations to Céline Barthelemy, Abdoulaye Oury BARRY and Bruno André as well as to our deputy director Laure Twyffels who contributed to the confocal fluorescence microscopy part.

The study explores the effect of the anticancer agent FTY720 on yeast and human cells. FTY720 was already known to “starve cancer cells to death” (10.1002/1873-3468.12121).  The present study better explains how: it shows that FTY720 reduces the activity of several plasma membrane amino acids permeases. This decreases the ability of cells to import amino acids, which, in turn, triggers a positive feed-back mechanism that leads to the endocytosis of these permeases via the inhibition of TORC1, and a further decrease in amino acid import capability.


11A picture acquired at the CMMI is featured as the cover of Nature Microbiology this week. Congratulations to our electron microscopy team !