Jun Prof Neva Caliskan
Recoding Mechanisms in Infections
When a cell is infected by a virus or bacteria the gene expression of the pathogen and the infected cell is altered, thus leading to changes in cellular transcription and translation. As a result, the RNA and protein composition in infected cells will be different from non-infected cells. mRNA structure and regulatory RNA elements play a critical role in defining how and when an mRNA will be translated in response to infections. Our team employs a multi-disciplinary approach to understand the functions and dynamics of RNA molecules in non-canonical translation events in the interplay of the host and the pathogen. Our ultimate aim is to identify novel therapeutic RNA targets to combat infections.
Our research and approach
RNA is the central molecule that transfers genetic information into functional proteins of host cells and pathogens. The message encoded in the RNA can be read in multiple ways through alternative translation strategies. This adds a hidden-layer to post transcriptional gene expression and alters the proteome composition significantly during infections. The versatility of RNA molecules allows for a dynamic translational regulation in time and space and enables the pathogen and the host to respond faster to changes upon infection. With the outbreak of superbugs and emerging viruses, there is an urgent need to develop new therapeutic strategies to combat infections. Can targeting alternative translation pathways be an option to combat deadly pathogens? Can we specifically interfere with mRNA structures as a novel anti-infective strategy? We seek answers to these questions by developing methods to investigate RNA structure and translation in real time (Caliskan et al.,2014,Caliskan et al., 2017) using a multidisciplinary approach ranging from single molecules to cells.
Small synthetic molecule-stabilized RNA pseudoknot as an activator for -1 ribosomal frameshifting
Matsumoto S, Caliskan N, Rodnina M, Murata A, Nakatani K (2018)
Nucleic Acids Res, 46 (16): 8079-8089DOI: 10.1093/nar/gky689
Conditional Switch between Frameshifting Regimes upon Translation of dnaX mRNA
Caliskan N, Wohlgemuth I, Korniy N, Pearson M, Peske F, Rodnina M (2017)
Mol Cell, 66 (4): 558-567DOI: 10.1016/j.molcel.2017.04.023
Choreography of molecular movements during ribosome progression along mRNA
Belardinelli R, Sharma H, Caliskan N, Cunha C, Peske F, Wintermeyer W, Rodnina M (2016)
Nat Struct Mol Biol, 23 (4): 342-8DOI: 10.1038/nsmb.3193
Many bacterial and viral pathogens and also their eukaryotic host cells employ non-canonical translation strategies in order to express hidden genes from alternative open reading frames (Caliskan et al., 2015). RNA is a versatile molecule that acts as a key regulator of non-canonical translation events. RNA can exist in various shapes and interact with other regulatory elements such as ncRNAs, small molecules and proteins to alter the meaning of the message encoded in the primary sequence of the mRNA. How RNA structure and regulatory elements drive alternative translation events is currently not fully understood. In addition, it is largely unclear to what extend these translation events are used by the pathogen and the host cell during infections. We use cutting-edge RNA analytics, such as ribosome profiling and deep sequencing combined with single molecule and computational tools to understand dynamics of translation and the functions of RNA regulators during infections. Ultimately, we want to better understand the interplay between the host’s and pathogen’s gene expression and harness our knowledge to develop novel therapeutic strategies to combat infectious diseases.