Mitochondria are cellular power plants. We have hundreds to thousands of them in each cell. It is inside of mitochondria that the sugar and fat we eat are burned and generate energy used to create a compound – ATP. ATP can be thought of as a universal battery that powers most biological processes in our cells.
Michał Roman Szymański
Mitochondria are unique in the way that they have their own DNA, in which the information on how to build the key components of electron transport chain, the ATP production sites, is encoded. However, free radicals generated during the process of ATP production tend to escape from these cellular power plants. At low concentration, free radicals are thought of as signalling molecules but at high concentrations they damage mitochondrial DNA. DNA in mitochondria, just like in the nucleus, must be faithfully copied and mistakes lead to formation of DNA lesions. Persistence of these DNA lesions may lead to genomic instability and different disorders with a wide range of clinical symptoms, and has been connected to cancer and premature aging, as well as cardiovascular, skeletal muscular and neurological disorders. It has been shown that mitochondrial DNA can be efficiently repaired but our understanding of this process is rather limited.
The goal of this project was to provide fundamental mechanistic information on how two proteins (hEXOG and Polγ), thought to be involved in the process of DNA repair in mitochondria, work and cooperate with each other to process damaged DNA substrates. We have shown that both proteins cooperate in removing DNA lesions. This cooperation is dynamic and dependent on the type and the size of the damage. Our findings have also shown that there are probably other, additional proteins, that would facilitate DNA damage repair and this possibility is being examined further in my group.
What’s the biggest success of your project?
We have had several scientific achievements in the project. Research-wise, not only were we able to uncover the mechanism of DNA damage removal in human mitochondrial DNA but also identified additional factors that could modulate this process. In addition, we continued old collaborations and extended our scientific network. However, probably the biggest success of the project is the development of my scientific programme and the setting up of my independent research group supported by external research funding from the Foundation for Polish Science, EMBO and ERC.
Why are the results of your research important?
Strict preservation of genetic information is critical for maintenance of species and faithful inheritance of genetic material through generations. DNA replication, recombination and repair are tightly regulated fundamental processes coordinated by multiple protein complexes. Understanding how these enzymes cooperate to perform their function is indispensable for understanding why such processes dysfunction in various diseases such as cancer and human genetic disorders.
Understanding how DNA replication, recombination and repair enzymes perform their function may inform us on how to regulate and control these processes and, thereby, design efficient disease therapies.
How did you benefit from the POLONEZ fellowship?
POLONEZ helped me in the transition stage from postdoc to the PI and from USA to Poland. Thanks to the fellowship I was able to build a small research team and expand my scientific network through collaborations. In addition, thanks to the support of the POLONEZ fellowship I could commit more time to research and additional activities. For instance, I filed my habilitation and I applied for additional funding (EMBO Installation Grant). With the support of the POLONEZ fellowship I was able to generate ideas and preliminary data to support my application for the ERC Starting Grant which I received in 2019.
Dr hab. Michał Roman Szymański, prof. UG completed his studies in Biochemistry and Biophysics at the University of Houston, USA (2007) and earned his PhD in Biochemistry and Molecular Biology from the University of Texas, USA (2011). He was awarded the prestigious Jeane B. Kempner Postdoctoral Fellowship and continued his research at the Department of Biochemistry and Molecular Biology and later Department of Pharmacology at the University of Texas Medical Branch (USA). In 2017, as winner of POLONEZ (National Science Centre, Poland) and FIRST TEAM (Foundation for Polish Science) grants, he joined the Intercollegiate Faculty of Biotechnology UG & MUG Gdańsk, Poland. Apart from Polish and American fellowships and grants, he won the prestigious European Research Council Starting Grant and the EMBO Installation Grant. Since 2019, he has headed an independent Structural Biology Laboratory at the Intercollegiate Faculty of Biotechnology UG & MUG Gdansk, Poland.