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.


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 (☺!)

Humans are protected against African trypanosomes by the serum protein APOL1; however, Trypanosoma rhodesiense and Trypanosoma gambiense neutralize this defense and cause sleeping sickness. Fontaine et al. found that APOL3 is also able to kill both species and consequently engineered a therapeutic version of APOL1 that eradicates infection by T. gambiense in mice.

APOLs with low pH dependence can kill all African trypanosomes

TEM imaging of T.b. brucei during lysis

Frédéric Fontaine, Laurence Lecordier, Gilles Vanwalleghem, Pierrick Uzureau, Nick Van Reet, Martina Fontaine, Patricia Tebabi, Benoit Vanhollebeke, Philippe Büscher, David Pérez-Morga and Etienne Pays

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!