Melody Cools received her PhD diploma

On March 30th, Melody Cools publicly presented her PhD work and successfully received her diploma. Her research dealt with the role and regulation of amino acid transporters of the yeast vacuole used as a model to better understand equivalent proteins in the human lysosome. Study of these lysosomal transporters is important to better understand the cellular disorders caused by cystinosis, a human genetic disease. Melody will soon move to the lab of Pr. Joris Winderickx (KUL, Leuven) for a postdoc. Thanks a lot to her for her investment in this novel research topic of the lab.  

Study on a novel pathway activating TORC1 published in eLife

Final Model Saliba
The TOR kinase complex 1 (TORC1), conserved in all eukaryotic cells, plays a central role in control of cellular growth and autophagy according to nutrient availability, and its dysfunction is associated with several diseases. The activity of TORC1 is typically stimulated when amino acids are provided to amino-acid-starved cells. However, the signal eliciting this TORC1 reactivation in yeast has remained largely unknown. We now report in eLife that it is the influx of H+ coupled to amino acid uptake (via amino-acid/H+ symporters) that triggers this TORC1 activation, and that the plasma membrane H+-ATPase establishing the H+ gradient is a central actor of this mechanism. We propose the model that this H+-ATPase “senses” H+-coupled nutrient uptake and transmits this signal to TORC1. This study opens new perspectives for the study of nutrient sensing and growth control in other species.
This work has been mainly accomplished by Elie SALIBA, who recently defended his PhD thesis. It also involved a collaboration with Dr. Isabelle Georis (IRMW institute).  

Article : The yeast H+-ATPase Pma1 promotes Rag/Gtr-dependent TORC1 activation in response to H+-coupled nutrient uptake. Elie Saliba, Minoas Evangelinos, Christos Gournas, Florent Corrillon, Isabelle Georis &Bruno Andre. Elife (in press).     

Study on membrane microdomains protecting transporters from ubiquitylation and endocytosis published in PNAS

Can1 in EMC
The plasma membrane of cells is known to be compartmentalized into domains enriched in specific lipids and proteins. The best studied membrane domains found in yeast is the “Eisosome Membrane Compartment” (EMC) accumulating diverse proteins including several nutrient transporters. However, how and why these transporters preferentially partition in these EMCs remains unknown.

In a novel study published in PNAS and mainly conducted by Christos Gournas (FNRS postdoc), we report that segregation of the Can1 arginine transporter into EMCs is dictated by its conformation and requires proper biogenesis of sphingolipids. Furthermore, this clustering confers to Can1 and other transporters protection from ubiquitin-dependent endocytosis. This protective role is particularly pronounced under nutrient starvation conditions, where EMCs increase in size and number. It allows cells to preserve a fraction of their nutrient transporters from bulk endocytosis occuring in parallel with autophagy, and to more efficiently resume growth when replenishing compounds are available. This work reveals nutrient-regulated protection from endocytosis as an important role for protein partitioning into membrane domains. It also suggests that EMC-like microdomains existing in human cells could ensure a similar function. This study was supported by the FNRS and conducted in collaboration with the Centre for Microscopy and Molecular Imaging (CMMI) of the Biopark and with Dr. D. Tyteca (UCL, De Duve Institute).     

Article : Conformation-dependent partitioning of yeast nutrient transporters into starvation-protective membrane domains. Gournas C, Gkionis S, Carquin M, Twyffels L, Tyteca D, André B. PNAS (in press). 

“Cystinosis Research Foundation” 2018 symposium

Bruno André attended to the last scientific symposium organized by the “Cystinosis Research Foundation” (Irvine, USA, March 1-2). The meeting gathered all the research groups supported by the CRF and conducting fundamental or clinical research studies on cystinosis, a rare genetic disease caused by mutations in the CTNS gene. This gene encodes a transporter present at the lysosomal membrane and catalyzing export to the cytosol of cystine, the compound made of two cysteines linked by a disulfide bridge. B. André presented the work carried out in his lab about cysteine transport across the vacuolar membrane in yeast cells. 

Elie Saliba received his PhD diploma

Elie thesis Dec 2017
On December 20th, Elie Saliba publicly presented his PhD work dealing with a novel mechanism of activation of the TORC1 kinase complex in yeast. He has successfully received his PhD diploma. A great moment for Elie, who was surrounded by his wife, colleagues, and friends. Elie will stay in the lab for a postdoc where he will pursue his work about the role of H+ ATPases in activation of TORC1. Thanks a lot to him for his key contribution to this novel research topic of the lab.  

Georgios Kapetanakis obtained a FRIA fellowship

photo George Kapetanakis
Georgios Kapetanakis was informed by the FNRS that he’s among the laureates of the 2017 competition for FRIA fellowships. Georgios obtained his master diploma last year in the University of Athens (Greece). He did a master thesis work in the lab of Pr. G. Diallinas where he investigated the role of membrane transporters in resistance to specific drugs by the fungus Aspergillus nidulans. During his PhD, Georgios Kapetanakis will investigate the molecular mechanisms of the still-poorly understood phenomenon of amino acid excretion by yeast, in the context of a collaboration with Dr. Isabelle Georis of the IRMW institute (Anderlecht).  

ASCB 2017 meeting in Philadelphia

B André attended the annual meeting of the American Society of Cell Biology (ASCB) in Philadelphia (2-6 December). The EMBO was a coorganizer of this major annual cell biology meeting.   

Charlotte Felten hired by the lab as technician

We are pleased to announce that the lab has hired Charlotte FELTEN as a new technician. Charlotte obtained her diploma in 2017 at the “Haute Ecole de Louvain en Hainaut” (Fleurus). She did an internship in the Immunobiology group of our institute. Charlotte now joined the lab thanks to a new four-year grant from the Wallonie Region.

Study on FTY720 anticancer drug provoking endocytosis of amino acid transporters in yeast and human cells published in Scientific Reports

FTY720 is a drug causing death of several types of tumour cells. This effect is largely due to its ability to provoke endocytosis of several nutrient transporters. FTY720 also promotes endocytosis of amino acid permeases in yeast. In a study now published in Scientific Reports, Céline Barthelemy and coll. report that FTY720 inhibits the intrinsic activity of  transporters, in both yeast and human cells. This is coupled to rapid inhibition of the TORC1 kinase complex, in turn promoting endocytosis of the inactivated transporters. This study sheds new light on how FTY720 kills cancer cells.       

“Endocytic trafficking and signaling in health and disease” meeting

Céline Barthelemy attended the EMBO conference presenting the last research progress about “Endocytic trafficking and signaling in health and disease” that was held in Serock, Poland (10-15 September). Céline presented in a poster her last results about the mechanisms through which the anticancer drug FTY720 provokes endocytosis of amino acid transporters in yeast and human cells.