Category Archives: news

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 !

NobelPrizesThanks to the continued support of the Walloon Region and the ERDF, the CMMI will soon propose cryo-TEM services to its academic and industrial partners.

We are therefore very happy to share that the Nobel Prize in Chemistry 2017 was awarded to Jacques Dubochet, Joachim Frank and Richard Henderson “for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution”. We too find that it is a “super cool” technology (☺!)

Summer publications of the CMMI… Congratulations to our collaborators !

Summer publications of the CMMI… Congratulations to our collaborators !

Nanofitin as a new molecular imaging agent for diagnosis of EGFR overexpressing tumors.
Goux M, Becker G, Gorré H, Dammicco S, Desselle A, Egrise D, Leroi N, Lallemand F, Bahri MA, Doumont G, Plenevaux A, Cinier M, Luxen A.
Bioconjug Chem. 2017 Aug 21. doi: 10.1021/acs.bioconjchem.7b00374.

Synthesis and characterization of monophosphinic acid DOTA derivative: A smart tool with functionalities for multimodal imaging.
Chilla SNM1, Zemek O2, Kotek J3, Boutry S4, Larbanoix L4, Sclavons C4, Elst LV4, Lukes I3, Muller RN4, Laurent S5.
Bioorg Med Chem. 2017 Aug 15;25(16):4297-4303. doi: 10.1016/j.bmc.2017.06.008. Epub 2017 Jun 15.

Dual RNA Processing Roles of Pat1b via Cytoplasmic Lsm1-7 and Nuclear Lsm2-8 Complexes.gr4Vindry C1, Marnef A2, Broomhead H1, Twyffels L3, Ozgur S4, Stoecklin G5, Llorian M1, Smith CW1, Mata J1, Weil D6, Standart N7.
Cell Rep. 2017 Aug 1;20(5):1187-1200. doi: 10.1016/j.celrep.2017.06.091.

Long-Term In Vivo Monitoring of Adult-Derived Human Liver Stem/Progenitor Cells by Bioluminescence Imaging, Positron Emission Tomography, and Contrast-Enhanced Computed Tomography.Longitudinal tracking of ADHLSCs by BLIHsu MJ1, Prigent J1, Dollet PE1, Ravau J1, Larbanoix L2,3, Van Simaeys G2,4, Bol A5, Grégoire V5, Goldman S2,4, Deblandre G1, Najimi M1, Sokal EM1,6, Lombard CA1.
Stem Cells Dev. 2017 Jul 1;26(13):986-1002. doi: 10.1089/scd.2016.0338. Epub 2017 Jun 5.



The CMMI is proud to announce the publication of an article to which it contributed

The CMMI is proud to announce the publication of an article to which it contributed:

CDK4 phosphorylation status and a linked gene expression profile predict sensitivity to palbociclib.

Raspé E, Coulonval K, Pita JM, Paternot S, Rothé F, Twyffels L, Brohée S, Craciun L, Larsimont D, Kruys V, Sandras F, Salmon I, Van Laere S, Piccart M, Ignatiadis M, Sotiriou C, Roger PP.
EMBO Mol Med. 2017 May 31. pii: e201607084. doi: 10.15252/emmm.201607084.
PMID: 28566333
We contributed to the development and execution of an assay that measures the sensitivity of cancer cell lines to a chemotherapeutic agent named palbociclib or PD0332991.

How does it work?
The assay is based on the fluorescent detection of BrdU, a nucleotide analog that can be incorporated into the DNA by cells that are actively replicating their DNA. An additional DAPI staining of all nuclei is performed. As a result, the nuclei of DNA-replicating cells emit green and blue fluorescence, while other nuclei emit blue fluorescence only.
Here, the classical BrdU incorporation assay was adapted into a 96-well format, in order to establish dose-response curves for >20 breast cell lines treated with various doses of palbociclib (PD0332991). The CMMI contributed to image acquisition and analysis, which was performed via a custom-made ImageJ routine. The ouput was a measure of the proportion of cells in S-phase for each experimental condition.

And the results?
We verified that our assay was more sensitive than the classical sulforhodamine and MTT assays, which only reflect cell accumulation and viability, respectively. The results confirmed our collaborators’ hypothesis that the T172 phosphorylation of CDK4 (which is the molecular target of PD0332991) correctly predicts the sensitivity or insensitivity of the cells lines to palbociclib.
Finally, to overcome the difficulty of using post-translational modification analysis of CDK4 in the clinic, our collaborators developed a surrogate CDK4 modification signature based on the expression of 11 genes. The signature correctly predicts the CDK4 modification profile of tumors and breast cancer cell lines, and the sensitivity of the latter to palbociclib. It may therefore be adapted to optimize the use of palbociclib in the clinic and extend its current indication to additional types of breast tumors.

Congratulations to Pierre Roger and his team, and in particular to Eric Raspé!

On Friday 24th of March, we were honored to welcome Mrs Corina Creţu, EU Commissioner for Regional Policy, accompanied by M. Paul Magnette, Minister-President of the Walloon Region. The purpose of the visit, which also included a tour in Charleroi, was to show how the European Regional Development Funds were used to foster the economic reconversion of Charleroi into sectors such as scientific research in Life Sciences. Mrs Creţu and her team seemed impressed by the development of the Biopark. They were also curious about the various techniques and instruments we showed them. A very agreeable visit!