GA CR Presidium is awarding three projects performed at FoM MU

The decision of the GA CR presidium declared the evaluation of the three projects solved at MF MU and awarded this reaching of extraordinary results which meets high demands put on scientific and research activities. Congratulations go to projects solved by Professor David Šmajs, M.D., Ph.D., Associate Professor Lumír Krejčí, M.Sc., Ph.D., and by Zuzana Koledová, M.Sc., Ph.D. which received the excellent rating within the final project evaluation.

2 Sep 2020

The assessment of finished grant projects is done, based on evaluation panel judgement, by the Czech Grant Agency specific expert commission, where the project belongs to. GA CR evaluates the final report and process of grant project solutions. The excellent evaluation is given to a project solution were the declared aims as well as the initial significant results moving forward the cutting-edge research were reached. These results are supported by publications within the relevant field and are considered as excellent from the point of view of the extent of information, the quality, and the potential resonance or possibilities for the usage when solving issues listed by these projects. Their significant impact on future field development, mainly in international context, must be mentioned as well. Usually, no more than a fifth of evaluated projects reaches this level of recognition. 

This evaluation also included three projects realized at the Medical Faculty MU, which were registered to a public tender for the research, the experimental development and the innovations supporting grant projects in a basic research. Two out of these projects were performed at the Department of Biology as Standard Projects. The first project solved by Professor David Šmajs, M.D., Ph.D.: Single cell techniques in whole genome sequencing of uncultivable pathogenic treponemes, and the second mentioned project solved by Associate Professor Lumír Krejčí, M.Sc., Ph.D.: Intrinsic properties of RAD51 filament and its biological regulations. The third awarded project was realized as a Junior project dedicated to FGF signalling in mammary fibroblasts and its role in mammary gland development and cancer performed by Zuzana Koledová, M.Sc., Ph.D. from the Department of Histology and Embryology.

Read the abstracts of the three mentioned projects here:

Professor David Šmajs, M.D., Ph.D.: Single cell techniques in whole genome sequencing of uncultivable pathogenic treponemes

Bacteria of the genus Treponema are known human and animal pathogens. While human and nonhuman primate pathogenic T. pallidum has been intensively studied for decades, there is little information on treponemes that naturally infect wild rabbits and hares (lagomorphs). Infection, however, is widespread in Europe. The rabbit pathogenic treponemes are not infectious for humans despite the fact that these treponemes show genome sequence identity with human T. pallidum higher than 98%. Therefore, an analysis focused on treponemes infecting lagomorphs will reveal not only characterization of these animal pathogens but will also help to better understand the evolution and biology of human infecting T. pallidum. There are three specific aims of the submitted project including i) testing of seroprevalence of rabbit and hare treponematoses, ii) analysis of diversity of infecting strains or isolates, and iii) genomic analysis of selected samples. In summary, we are planning to screen over 2,000 lagomorph samples and characterize about 90 DNA-containing samples.

The goal of this proposal is i) to test seroprevalence of rabbit and hare treponematoses, ii) to perform analysis of strain diversity of the causative agents and iii) to analyze genomes of treponemes with respect to the potential evolutionary scenarios leading to evolution of these pathogens.

Associate Professor Lumír Krejčí, M.Sc., Ph.D.: Intrinsic properties of RAD51 filament and its biological regulations

Homologous recombination (HR) is an essential mechanism for the repair of DNA double-strand breaks and damaged replication forks. HR is initiated by the formation of a RAD51 helical nucleoprotein filament on single stranded DNA, which is able to search for and invade homologous duplex DNA to form a joint molecule. Although, RAD51 is unable to work alone and is reliant on co-factors (BRCA2 and RAD51 paralogs,) to drive the HR reaction to completion a mechanistic understanding of how this is achieved is unclear. This project brings together the unique expertise to investigate how the properties of the RAD51 nucleoprotein filament are modulated by HR co-factors. Integration of real-time kinetic measurements, microscale thermophoresis, single molecule and structural visualization studies, conformational dynamics, and validation in biological systems will provide unprecedented insight into the mechanisms by which HR co-factors impact on the HR reaction and its relevance to development of cancer and other genome instability-associated diseases.

Zuzana Koledová, M.Sc., Ph.D.: FGF signalling in mammary fibroblasts and its role in mammary gland development and cancer

The overall aim of the project was to investigate the existence and function of fibroblast growth factor signalling (FGF) in stromal fibroblasts of the mammary gland and its role in mammary gland development and cancer.

FGF signalling is an essential signalling pathway that mediates communication between cells, from the earliest developmental stages throughout life. Its proper function is crucial for organ development, homeostasis and regeneration, and its deregulation leads to pathologies, including cancer. In the mammary gland, FGF signalling had been known to play a role only in the epithelium. In this project, for the first time, Dr. Koledova reported and deciphered the role of FGF signalling in mammary fibroblasts in regulation of mammary epithelial branching morphogenesis, a process through which the functional architecture of the milk-producing organ is established. 

To this end, the researchers had developed and used innovative 3D cell cultures, including co-cultures of mammary organoids with mammary fibroblasts, in combination with advanced imaging and molecular biology techniques. The results of this project, published in the prestigious journal Development (Q1: #4/86 in developmental biology, IF 5.763), challenge the dogmatic epithelium-centric view on the role of FGF signalling in mammary gland development. This work documents that FGF signalling is required for regulation of crucial fibroblast functions, too, which in turn impact on epithelial development.

Furthermore, the project has helped to elucidate the phenomenon of bi-phasic dose-response profile of FGF signalling. Using hyperstable variants of FGF2 in collaboration with the biotech company Enantis, Dr. Koledova uncovered new mechanisms, which regulate cellular outcomes of FGF signalling. These results were published in the journal Frontiers in Cell and Developmental Biology (Q1: #46/264 in cell biology, IF 5.206).

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