Projects / Programmes
ANALIZA DELOVANJA PROTEINA AIRE NA RAVNI CELOTNEGA GENOMA IN NJEGOVA VLOGA PRI URAVNAVANJU GENSKE MREžE V TIMUSU (Slovene)
| Code |
Science |
Field |
Subfield |
| 4.06.03 |
Biotechnical sciences |
Biotechnology |
Animal biotechnology |
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
24298 |
PhD Irena Oven |
Animal production |
Head |
2009 - 2011 |
81 |
Organisations (1)
Significance for science
Central tolerance is an important immune mechanism that has significantly gained value in the field of scientific research. This was enabled by the discovery of novel transcription factor, AIRE that regulates the expression of tissue specific antigens in the thymus. Thymus is the site for maturation and negative selection of T cells. Before the discovery of AIRE protein, the immunologists attributed most of the functions, now known to be part of central tolerance mechanisms (these include the elimination of self-reactive T cells), to the mechanisms of peripheral tolerance. With the discovery of AIRE, the view has changed drastically. Therefore, this area of research has become very popular in the last few years, and a great number of new studies and new facts have been published in the last three years. Since this area of research is still relatively new, a lot of open questions remain. One of the key unknowns is to figure out how one transcription factor can specifically activate the expression of over 200 genes that are seemingly unrelated by their site of expression and mode of action as well as the control of their expression in their target tissues. In the past it was thought that transcription factors regulate expression of genes by binding to a specific site on the promoter. If the sequence is not present in the specific promoter, transcriptional activator cannot bind to the regulatory region, which is of course well thought from the point of gene expression control that has to be regulated in a spatial and timely manner. AIRE protein is special since it can activate the expression of over 200 tissue-specific genes in the thymus, in a manner that is distinguished from the regulation of that particular gene in its tissue. This implicates a certain degree of deregulation of gene-expression. In certain genetic diseases and cancers deregulation of gene expression can occur, which leads to non-specific mode of action (of before specific transcription factors). Consequences of this deregulation can lead to onset of a disease. It is possible that living organisms have used some kind of deregulation to its advantage (for the expression of tissue-specific genes in the thymus). Therefore, the understanding of mechanism, how AIRE activates the expression of tissue specific genes in the thymus, might help us to elucidate the events that precede deregulation of gene expression in certain diseases. In addition, mutations in human AIRE protein cause the development of rare autoimmune disease APECED, where the mechanisms of central tolerance are disrupted and autoimmune attack towards several self-organs can occur. By knowing all genes, regulated by AIRE, and the mode of action, how this expression is regulated, we could develop novel molecular diagnostic methods and screenings for earlier detection of APECED in patients and develop novel therapeutic approaches for treatment of APECED. To establish an overview of the AIRE-regulated genes, a whole genome approach analysis has to be carried out.
Significance for the country
In Slovenia, the prevalence of APECED disease is relatively high. The researchers estimate the prevalence of APECED in Slovenian population to be 1 in 43,000, which is significantly higher compared with the neighboring populations. The estimated prevalence is significantly higher compared with the Norwegian population (1 in 80,000) or neighboring populations where, with the exception of the Northern Italian population only isolated APECED cases were described. This shows that the understanding of molecular mechanism of AIRE action has an important impact not only from the point of global understanding of immune tolerance, but can also significantly contribute to the development of novel diagnostic methods and novel therapeutics for treatment of APECED. Our study will create basic knowledge, relevant to our social environment that will be potentially interesting for implementation to Slovenian clinical practice. New discoveries from the study would enable formation of novel treatments or disease prevention methods and consequently improve the quality of life in such cases. Since we are included in the teaching process in Biotechnical faculty, the results of the study are also, as is often the case with our other studies, presented in seminars and in student laboratory work as well as in lectures.
Most important scientific results
Final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
final report,
complete report on dLib.si
