Jun Prof Neva Caliskan
Recoding Mechanisms in 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.
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.
Structural studies of Cardiovirus 2A protein reveal the molecular basis for RNA recognition and translational control
Hill CH, Napthine S, Pekarek L, Kibe A, Firth AE, Graham SC, Caliskan N, Brierley I (2020)
Structural and molecular basis for protein-stimulated ribosomal frameshifting in Theiler’s murine encephalomyelitis virus
Hill CH, Cook G, Napthine S, Kibe A, Brown K, Caliskan N, Firth AE, Graham SC, Brierley I (2020)
Schmidt N, Lareau CA, Keshishian H, Ganskih S, Schneider C, Hennig T, Melanson R, Werner S, Wei Y, Zimmer M, …, Bodem J, Munschauer M (2020)
Nature Microbiology 6 (3): 339-353
Matsumoto S, Caliskan N, Rodnina MV, Murata A, Nakatani K (2018)
Nucleic Acids Research 46 (16): 8079-8089
Belardinelli R, Sharma H, Caliskan N, Cunha CE, Peske F, Wintermeyer W, Rodnina MV (2016)
Nature Structural & Molecular Biology 23 (4): 342-8