Jan KadlecInstitut de biologie structurale (IBS) - CNRS / CEA / Université Grenoble Alpes
Mes recherches
Main focus of my research is on structural characterization of protein complexes involved in epigenetic regulation. I did my PhD in the group of Stephen Cusack at the EMBL Grenoble Outstation (2001-2005) studying proteins involved in RNA quality control. I then moved to University of Oxford (2005-2007), where under supervision of David Stuart I worked on structural characterization of viral fusion proteins. In 2008, I returned to EMBL as a staff scientist and initiated my research on epigenetic regulatory complexes. In 2014, I obtained the Atip/Avenir start-up grant and in 2015, I joined the Institute of Structural biology in Grenoble, where I established the “Epigenetic regulators” research team. I was recruited as a researcher by the INSERM in 2015. Since then, I also developed new structural projects on RNA degradation and meiotic recombination.
Mon projet ATIP-Avenir
Structural and functional studies on epigenetic regulators.
In Eukaryotes, DNA exists in the form of chromatin whose dynamics and chemical modifications control access to and the interpretation of the DNA information. Indeed, dynamic chromatin structure is essential for the regulation of most DNA associated processes, such as transcription, replication or DNA repair. Various post-translational modifications of histones and DNA exist that can change the chromatin structure and recruit effector proteins, such as transcription factors. While genome-wide research in the field of chromatin and epigenetics generated a wealth of data on new regulatory pathways and their implications in development or disease, the molecular details of the mechanisms involved are often poorly understood. The proposed project will use an interdisciplinary approach combining biochemical and structural analyses with cell biology, genetics and clinical studies to provide mechanistic insight into important chromatin modifying enzymes with regard to their epigenetic regulatory functions and their role in human disease. These studies will shed light on the general principles underlying the epigenetic control of DNA based processes in Eukaryotes. Specifically, we will focus on two MOF histone acetyltransferase containing complexes, the Male Specific Lethal (MSL) complex, which plays a key role in X-chromosome dosage compensation in Drosophila, and the Non-Specific Lethal (NSL) complex, which is involved in global transcription control, embryonic stem cell pluripotency and DNA repair with implications in genetic disease and cancer development. In parallel, we will structurally and functionally characterize several members of the PRDM histone methyltranserase family such as PRDM1, -9 and -14 to reveal molecular details of their diverse roles in cell differentiation, meiotic recombination or cancer. The proposed research will be carried out at the Institut Albert Bonniot in Grenoble, which provides an exceptional scientific environment for epigenetics and cancer research with expertise in cell biology, genetics and clinical research, yet is in proximity to the synchrotron beamlines, structural and biophysical platforms and the structural biology community of the Partnership for Structural Biology (PSB) in Grenoble.