People - Incoming

Dinesh DHURVAS CHANDRASEKARAN

Dinesh Dhurvas Chandrasekaran will carry out the research focused on the development of the new molecules that have a broad-spectrum virostatic effect. This research is in accordance with a RIS3 national strategy in a key application sector Drugs and medical products and methods for healthy ageing (NIP IV. – Drugs, Biotechnologies, healthcare, Life Sciences). This topic belongs among the main areas of research at IOCB. Dr. Chandrasekaran will first prepare recombinant proteins from several important pathogens that belongs in picornaviruses and flaviviruses (e.g. poliovirus, yellow fever virus, Zika virus). These proteins will be mainly polymerases, methyl transferases and helicases. At the second stage, Dr. Chandrasekaran will focus on the biochemical analysis of the small molecules prepared at IOCB (in cooperation with Nencka group dealing with organic synthesis of virostatic). This action wi aim at that are aimed against the prepared proteins. This stage will include determination of the inhibition and dissociation constants and other thermodynamic characteristics. Next step will consist of structure analysis of small molecule-protein complexes using roentgen crystallography. The defined structures will serve for the following rational design and preparation of more inhibitors with improved features that will be tested in tissue cultures and mouse models in cooperation with Dr. Růžek (Veterinary institute Brno).

Mouna OUCHARI

Mouna Ouchari will focus on the Flaviviruses such as Dengue virus or Zika virus. The genome of these viruses comprise only single strand positive RNA ((+)ssRNA) that represents genetic information as well as viral coding mRNA. Newly established research discipline epistranscriptomics studies the dynamics RNA modifications. Since 2012, e. g. N6-methyladenosin (m6A) has been identified as an epitranscriptomic mark, that influences fetal development or the outbreak of acute myeloid leukemia by means of the mRNA in eucaryotic cells. Moreover, it was proved that the increased concentration level of m6A in eucaryotic cells infected with Zika virus lead to the decrease replication rate of the virus. Isolation of the mRNA from eucaryotic cells in sufficient amount and purity for LC/MS analyses is not practically possible. However, (+)ss RNA viruses are packed with only mRNA. Our preliminary results shows that m6A is not unique mRNA modification, and (+)ss RNA viruses most probably comprise and use many other RNA modifications.
Within the project, we want to develop the process for isolation of genome RNA of Flaviviruses in sufficient amount and purity for LC/MS analyses of RNA composition. Following this process we aim at development and application of methods for determination of location of RNA modification in connections to next generation sequencing methods. We believe that the discovery of new RNA modifications in viruses leads to the better understanding of their structure and to the development of new strategies in their elimination.

Taye Beyene DEMISSIE

Taye B. Demissie will devote his stay to the spectral characterisation of molecules using quantum mechanics calculation and molecular dynamics simulation. Modern spectroscopic methods revealing the molecular features and structure would not work without simulation. However, exact simulations are demanding in computation time . Dr. Demissie’s stay is a follow-up of the previous cooperation of IOCB and the centre of theoretical and computational chemistry in Tromso, Norway. The activities will aim at conformation and spectroscopic features of protein aggregates. Protein aggregates plays an inmportant role in neurodegenerative diseases, such as Alzheimer disiese, Parkinson disease, Creutzfeldt-Jakob disease. However, their structure and features are not thorouglhy known. Main aim of the stay is developing general algorithms for simulations of electron and vibrational features of molecules. Application of the simulations will contribute to the development of new technologies and new diagnostic processes in medicine (e.g. comercial application of Raman spectroscopy has been launched recently in 2007 by Biotools, USA and in 2018, new generation of such devices shall be launched in 2018 by Meopta, Olomouc)

Tillmann BUTTERSACK

The stay of Tillmann Buttersack is aimed at construction of unique experimental device that enables studying the electrones solvated in liquid ammonia that are the key reduction agent in the whole class of organic reaction (so called Birch reduction). The device will enable the liquefaction of ammonia while mixing it with an alkali metal in the role of electron donor. Subsequently, the device will transfer the solution in the micro jet spray. This device will be set up at IOCB where the pilot experiments also takes place. Photoelectron spectra characterizing the solvated electrons will be measured at synchrotron BESSY in Berlin. Expected result is an exact characterization of the solvated electrons at various concentration arrangements ranging from isolated electrons through dielectrones up to conduction bands that are connected with metal character of the solution.