DNA replication and genome stability

We shall custom-engineer MAS and metabolomics NMR and apply it on selected problems, notably Alzheimer's, Parkinson's, COVID, diabetes and cardiovascular conditions, fluor ion batteries, wood chemistry, also universal AI-assisted diagnostics and monitoring. We shall in particular focus on phytochemicals as the fastest and least harmful option to address acute health issues like SARS infection and neurodegenerative diseases. New hardware, based on fast mechanical spinning up to 15 Million RPM, electron spin polarization transfer (DNP), a sophisticated multi-axes sample rotation (DOR) and also 1.2GHz NMR magnets are expected to provide an unprecedented resolution and sensitivity in NMR, rendering it principally more helpful for a significantly wider range of material sciences and biomedical topics. In complex functional cases, the NMR will be arguably more informative and convenient than presently popular methods of plasmon resonance, CryoEM, X-ray or MS.

DNA replication is one of the major targets of cancer therapies, as cancer cells tend to proliferate faster than normal cells and are generally more prone to replication stress. Most of our current knowledge about DNA replication initiation, or origin firing, currently comes from model organisms, such as yeast, but their applicability to the human system is limited. It is important to study replication initiation in human cells in order to be able to exploit the findings in cancer therapies. The main objectives of this project are to identify novel players in various stages of human replication initiation and characterize the non-catalytic roles of DNA polymerase epsilon and protein Timeless in replisome assembly.

A prototype allowing a rapid diagnostic possibility of COVID-19 has been developed. The principle of operation of the prototype differs drastically from widespread lateral flow COVID-19 express diagnostics tests currently available on the market. Namely, the prototype is a combination of sensor chip modified with the synthetic receptor and a portable potentiostat. The synthetic receptors were prepared by molecularly imprinting technology and targeted against nucleocapsid (N) and spike (S) SARS-CoV-2 viral proteins. It was shown that the prototype was capable of detecting the target proteins from patients’ nasopharyngeal samples in 15 min through measurement of the redox reaction intensity at the chip after its incubation in the mentioned sample. The prototype has the following advantages over lateral flow tests: (i) employment of the synthetic receptors as sensitive elements instead of their biological counterparts provides a more cost effective and stable diagnostics tool in whole; (ii) about hundredfold lower LOD allows diagnosis of COVID-19 at earlier stage; (iii) measurement of concentration of the proteins allows estimate viral load. Therefore, the prototype has the outstanding innovative potential for its further development to offer a reliable COVID-19 express diagnostic tool. Such a tool can be employed in clinical institutions for example in primary care physician practices, emergency medicine etc. The tool could be also developed for point-of-care and personal use at home as well in order to reduce load on healthcare systems and prevent additional risks for passing on the infection to other people. It should be noted that in this project we managed, for the first time to the best of our knowledge, to apply the molecular imprinting technology for detection of SARS-CoV-2 viral proteins. The results were published as a scientific paper in the top interdisciplinary journal devoted to biosensors, which has already received multiple citations.