čas: 23.4.2021 00:39:18
Obnovit | RAW
Institute of Biotechnology of the CAS, v. v. i.
List of available PhD theses
Structure and dynamics of glutamate receptors, theory and experiment.
The proposed multidisciplinary project combines various experimental and theoretical strategies to refine structural elements of the glutamate receptor (iGluR) in functionally important states. We will extend the available structural data using a mammalian and insect cells expressed iGluRs. We will induce and characterize its functional state (activation kinetics, binding affinity, and single channel properties). Further, we will use the distance information from a structural mass spectrometry analysis as an input into all-atom adaptive enhanced sampling MD simulations to refine the original crystal structures and identify new structural motifs. We will gain highly accurate structural information on iGluR in its functionally important states and their role in iGluR structural transitions.
Structure and function of bacterial transcription system
The bacterial transcription system is currently a focus of numerous research projects as an antibiotic target as well as posing a number of unanswered basic questions. We concentrate on analysis of structure and function of RNA polymerase from gram-positive bacteria, namely Mycobacterium smegmatis and Bacillus subtilis. We investigate the role of either recently discovered or not fully understood protein factors involved in the transcription machinery. Mycobacteria are medically important organisms containing serious pathogens. Bacillus subtilis is a representative organism of gram-positive bacteria, with some differences in transcription in comparison to mycobacteria. In this project selected RNA polymerase-associated proteins will be characterized in detail as for their structure and function, using techniques of molecular biology and integrative structural biology, including X-ray crystallography, small angle X-ray scattering and cryo-electron microscopy.
Transcriptome analysis of acute injuries of the central nervous system
The function of the central nervous system (CNS) is defined by the complexity of interactions between hundreds types of neurons, glial and vascular cells. The latest improvements in high-throughput gene expression technologies together with computational analyses allow to study the CNS complexity at unprecedented resolution. In this thesis, we aim to use the latest data collections and analysis techniques to conduct detailed transcriptomic description of ischemic brain injury and spinal cord injury in mice and rats. Firstly, bulk analysis will serve for coarse functional annotation of processes after injury. It will be complemented by deconvolution analysis to estimate cell type proportion changes and unsupervised co-expression analysis for identification of gene modules governing the response to injury. Network analyses will identify key drivers of the response and predict the mechanism of injury. Followed by generating single-cell and spatial transcriptomic datasets, coupled with the latest data integration tools, we aim to acquire detailed view on heterogeneity of response to ischemic and spinal cord injury at the single-cell level. Noteworthy, the observations will be related to various emerging cell atlases and thus complement incentives of the field.