Dimitris XirodimasCentre de recherche en biologie cellulaire de Montpellier (CRBM) - CNRS / Université de Montpellier
Mes recherches
My research combines studies in human cells with genetics in C. elegans to understand how organisms respond to environmental stresses that cause protein damage (proteotoxic stress) and how they maintain a healthy proteome (proteostasis). After a PhD degree (1996-2000) and postdoctoral studies (2000-2004) in the laboratory of Prof. Sir David P. Lane in the University of Dundee, Scotland/UK, I moved to Prof. Ronald T. Hay’s laboratory (St Andrews University, Scotland/UK) as senior postdoctoral fellow. In 2005, I obtained a 6-year career-development fellowship from the Association for International Cancer Research (AICR) to establish my independent research group at the School of Life Sciences in the University of Dundee, Scotald/UK. In 2010, I was recruited as a Director of Research 2nd class (DR2) by INSERM and obtained an ATIP/Avenir+ fellowship as Group Leader at the CNRS-Montpellier Cell Biology Research Center (CRBM). The fellowship allowed us to develop our group “Ubiquitin/Ubiquitin-like molecules and Protein Quality Control”, which is currently composed of 4 permanent researchers, 2 PhD students and 1 post-doctoral fellow. Our studies elucidate how ubiquitin and the ubiquitin-like protein NEDD8 regulate the detection, repair and elimination of misfolded proteins induced upon proteotoxic stress, processes that define the Protein Quality Control (PQC) system. Defects in PQC are hallmark of neurodegeneration and cancer and we anticipate our studies could identify potential therapeutic targets and strategies for such pathologies.
Mon projet ATIP-Avenir
The role of the ubiquitin-like molecule NEDD8 in transcriptional activity and cell growth regulation
Post-translational modifications of proteins with ubiquitin and ubiquitin-like molecules (Ubls) have emerged as major mechanisms of protein function regulation. It is now believed that these pathways are involved in the control of almost every biological process in the cell.
Amongst the family of Ubls, NEDD8 has the highest identity to ubiquitin but a distinct pathway exists that leads to the conjugation of NEDD8 to substrates. The well-established role of NEDD8 is the regulation of E3-ubiquitin ligases called CRLs (Cullin-Ring-Ligases) through modification of cullins. However, it has become evident that the NEDD8 proteome is more diverse than previously thought. Following on our NEDD8 proteomic studies, we discovered a key role for NEDD8 in regulating the function of the nucleolus as sensor of perturbations in cell growth. Our future goal is to expand on these findings and determine how NEDD8 impacts the signaling of cell growth defects to cell cycle regulators through the nucleolus. We anticipate providing insights on the emerging role for NEDD8 as regulator of stress responses and of the coordination between cell growth and the cell cycle.