Periodontitis, or gum disease, is one of the most common chronic inflammatory diseases known to mankind. It affects the tissues which support the teeth and, if left untreated, it can last for years causing gum recession and tooth loss.
Aleksander Grabiec
The disease is initiated by bacteria in dental plaque, especially Porphyromonas gingivalis, which accumulate on the surface of the teeth below the gum line. Although nearly 30% of adults suffer from periodontitis, in many countries it is a neglected disease, both by people in general and by health-care personnel, who often consider tooth-loss due to periodontitis to be an inevitable event associated with aging. However, the true impact of periodontitis on human health is immense as it is strongly associated with increased risk for other diseases, including rheumatoid arthritis, atherosclerosis and cancer. That is why it is necessary to better understand the causes of the disease and develop new strategies for its prevention and treatment.
In periodontitis, the damage of the periodontal tissue is a consequence of an ineffective host immune response to microbial invaders. However, little is still known about how these microorganisms affect biological processes inside host cells in order to avoid elimination by the immune system. One such process is epigenetic regulation of gene expression.
Genes provide instructions for cells on how to produce a variety of proteins which trigger biological processes to carry out life functions. Epigenetics influences how cells ‘read’ genes or how specific types of cells ‘know’ which genes to switch on to produce certain proteins and which to switch off. If we understood how to keep the good combinations of genes activated and how to eliminate the harmful ones we could, for example, influence the way cells respond to bacterial infection and determine the right treatment for many diseases.
The focus of this project was one of such epigenetic processes – acetylation of proteins that interact with DNA. We studied how oral bacteria manipulate protein acetylation in gingival cells and whether targeting this process could be beneficial in patients with periodontitis. First, we discovered a new mechanism of host cell manipulation by P. gingivalis – degradation of enzymes that regulate protein acetylation, histone deacetylases, which may significantly impact cell responses to infection with this pathogen. Second, we found that compounds which block the activity of acetylation regulators – histone deacetylases and BET proteins – reduce excessive production of mediators of inflammation and bone destruction by gingival cells from patients with periodontal disease. Since currently available therapies focus predominantly on reducing bacterial challenge, the anti-inflammatory activity of epigenetic drugs targeting acetylation could be considered a potential strategy for additional therapy that would support standard periodontitis treatment. These results not only improve our understanding of the pathogenesis of periodontal disease, but may also be important from the clinical perspective. Because some epigenetic drugs (histone deacetylase inhibitors) are already successfully used in the clinic to treat other diseases, these observations provide a rationale for future tests of drugs targeting histone acetylation in patients with gum disease.
How did you benefit from the POLONEZ fellowship?
The POLONEZ fellowship was the essential first step towards developing an independent scientific career and helped me secure funding for setting up my own research group in Poland. During the fellowship, I gained invaluable experience in project management and student supervision, which are essential parts of the scientific career as a group leader. At the personal level, the fellowship gave me a unique opportunity to return to my home town after 10 years of international work.
Dr Aleksander Grabiec is a cell biologist with a keen interest in epigenetic and transcriptional regulation in chronic inflammatory diseases. His research focuses on understanding how altered expression of epigenetic regulators, transcription factors and signalling molecules contributes to chronic inflammation, and on identification of novel therapeutic strategies targeting these alterations.
After obtaining an MSc in biotechnology at the Jagiellonian University in Kraków, Poland in 2007, he worked at the Academic Medical Center, University of Amsterdam, The Netherlands, where he earned his PhD in 2012. He continued as a postdoctoral researcher at the Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, UK. In October 2016, having received the POLONEZ fellowship, he joined the Department of Microbiology at the Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University. Together with the research group that he established within the Department of Microbiology, he now continues the research initiated during the POLONEZ project, with the support from grants from the Foundation for Polish Science (FIRST TEAM) and NCN (OPUS 18). He is the recipient of a 3-year scholarship from the Polish Ministry of Science and Higher Education for outstanding young scientists (2018) and the Polish Intelligent Development Award 2020 in the category: Researcher of the Future for his research on epigenetic mechanisms of gum disease.
