Research on hypusination will be funded by NCN
November 20, 2019
November 20, 2019
Dr. Przemysław Grudnik has been awarded an OPUS grant in the 17th edition of this prestigious contest. The project will focus on understanding the molecular and functional basis of protein network that regulates the synthesis of hypusine.
Hypusination is a modification described only for one protein: eukaryotic translational factor eIF5A and spermidine is used as a substrate in this process. – says dr. Grudnik. Because the process of hypunization is associated with excessive proliferation, growth and survival of cells, characteristic for tumour progression, the development of chemical molecules that regulate or block hypunization in the cell may also be important from a clinical point of view.
The researchers engaged in the project will use the structural biology methodology, including such techniques as X-ray crystallography, small-angle X-ray scattering (SAXS), mass spectrometry (MS) and cryo-electron microscopy (cryoEM).
In order to get molecular insights into the mechanism of hypusination we will solve the atomic structures of protein assemblies involved in this process. Then, using various biochemical tests, we will validate the structural data at the place of protein interaction, which will additionally confirm which regions of the proteins are necessary to form complexes. In addition, we intend to investigate the molecular basis of substrate binding by hypusinating machinery, as well as the effect of mutations described in neurological diseases on the structure and function of the proteins. In the last research task, we will carry out extensive screening tests aimed at finding new potential inhibitors of hypusination pathway – says grant manager.
The project called Molecular basis of hypusination will receive funding of 1 486 200 PLN.