Université de Strasbourg

Romeo Ricci

Biography

Institute of Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg

Romeo Ricci, USIAS Fellow 2017

Romeo Ricci studied human medicine at the University of Bern, Switzerland. After clinical training in surgical pathology at the University of Zurich, Switzerland, he joined the Research Institute of Molecular Pathology (IMP) in Vienna as a postdoctoral fellow in the research group of Professor Erwin F. Wagner. He subsequently worked at the Cardiovascular Research laboratory at the Institute of Physiology at the University of Zurich. Afterwards, he built up his own research laboratory at the Institute of Cell Biology at ETH Zurich where he received an Assistant Professorship in 2007. In 2010, he accepted a full professorship at the University Hospital of Strasbourg with a research group at the IGBMC.

Romeo Ricci’s research has discovered novel molecular mechanisms that contribute to the understanding of inflammatory disorders, atherosclerosis and diabetes. For his research activity so far, he has been awarded several distinguished research prizes, including being selected as a new EMBO Young Investigator in 2009 and the award of an ERC starting grant to his laboratory in 2012.

Project - Structural mechanisms of NLRP3 inflammasome assembly in vivo

April 2017 - March 2019

Our immune system evolved to maintain tissue homeostasis and function in response to inflammatory insults. The innate immune system is activated by the recognition of foreign molecular structures as well as improperly localized self-molecules through signaling receptors. These receptors monitor the extracellular space and many intracellular compartments for signs of damage, infections or other cellular stressors. The inflammasomes are a group of multimeric protein complexes formed in the cytosol that play critical roles in eliciting innate immune responses against pathogens and other damage-associated signals. The canonical inflammasome consists of a sensor molecule, the adaptor protein apoptosis-associated speck-like protein (ASC) and the effector molecule caspase-1. Upon activation, monomeric sensor protein oligomerizes to recruit the ASC and pro-caspase-1, leading to assembly of the inflammasome and subsequent auto-activation of caspase-1, which results in cleavage and secretion of pro-inflammatory cytokines interleukin-1β and interleukin-18, as well as cell death, called pyroptosis.

Distinct inflammasomes use different mechanisms to activate caspase-1. The NLRP3 inflammasome is unique in the sense that it is capable of detecting a broad variety of danger signals, including ATP, toxins and crystalline reagents. Activation of NLRP3 inflammasome has been shown to contribute to many human diseases, such as gouty arthritis, silicosis, asbestosis, type II diabetes mellitus, atherosclerosis, Alzheimer’s diseases and Cryopyrin-associated periodic syndromes (CAPS). Recently, we have discovered that Golgi-mediated PKD signaling is important for NLRP3 inflammasome activation. However, how the assembly of NLRP3 inflammasome occurs in vivo is still elusive.

In this USIAS project, we are aiming to explore the structural mechanism of NLRP3 inflammasome assembly in vivo. Using CRISPR/Cas9-based gene editing together with super-resolution microscopy, we are going to monitor the dynamics of different components and organelle compartmentation during NLRP3 inflammasome assembly. In addition, advanced electronic microscopy-based approaches will provide detailed structural mechanisms of the assembly of NLRP3 inflammasome in vivo. Overall, this project should give us unique insights into the spatially and temporally controlled mechanisms underlying NLRP3 inflammasome assembly in vivo, which may lead to potential pharmacological interruption strategies for NLRP3-related diseases in humans.

 

Post-doc biography - Zhirong Zhang

Institute of Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg

Zhirong Zhang, USIAS post-doc 2017

In 2013, Zhirong Zhang obtained his PhD degree under the supervision of Professor Jiahuai Han at Xiamen University, China. During his thesis, he was interested in cellular signaling and stress responses, focusing on the role of the autopahgic protein GABARAP in the activation of the NLRP3 inflammasome. After completing his PhD thesis, supported by a European Foundation for the Study of Diabetes (EFSD)/Chinese Diabetes Society (CSD)/Lilly Research Fellowship, he joined the group of Professor Romeo Ricci at IGBMC in 2013, working on the molecular mechanisms underlying the activation of NLRP3 inflammasome.

Within this USIAS project, Dr. Zhang is aiming to explore the structural mechanism of NLRP3 inflammasome assembly in vivo.

 

 

Links

Investissements d'Avenir