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Jun Prof Neva Caliskan

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.

Team members

Anuja Kibe

Anuja Kibe

PhD Student

Lukàš Pekárek

Lukàš Pekárek

PhD Student

Matthias Zimmer

Matthias Zimmer

PhD Student

Tatyana Koch

Tatyana Koch

Technical Assistant

Research projects

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. 

Publications

2019

Thermodynamic control of -1 programmed ribosomal frameshifting

Bock L, Caliskan N, Korniy N, Peske F, Rodnina M, Grubmüller H (2019)

Nature Communications, 10 (1): 4598

2018

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 Research, 46 (16): 8079-8089

2017

Conditional Switch between Frameshifting Regimes upon Translation of dnaX mRNA

Caliskan N, Wohlgemuth I, Korniy N, Pearson M, Peske F, Rodnina M (2017)

Molecular Cell, 66 (4): 558-567

2016

Choreography of molecular movements during ribosome progression along mRNA

Belardinelli R, Sharma H, Caliskan N, Cunha C, Peske F, Wintermeyer W, Rodnina M (2016)

Nature Structural & Molecular Biology, 23 (4): 342-8

2015

Changed in translation: mRNA recoding by -1 programmed ribosomal frameshifting

Caliskan N, Peske F, Rodnina M (2015)

Trends In Biochemical Sciences, 40 (5): 265-74

2014

Programmed -1 frameshifting by kinetic partitioning during impeded translocation

Caliskan N, Katunin V, Belardinelli R, Peske F, Rodnina M (2014)

Cell, 157 (7): 1619-31

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