Supervisors info:
Ανδρέας Σκορίλας, Καθηγητής Κλινικής Βιοχημείας, Τμήμα Βιολογίας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Summary:
Viral infections inflict a lasting negative impact on human health and are often responsible for the generation of waves of worldwide morbidity and mortality. Viruses cause transcriptional reprogramming of the host cells, which often leads to the development and establishment of severe pathogenic phenotypes such as those characterize well-known human diseases such as Type 1 Diabetes Mellitus (T1D), Acquired Immunodeficiency Syndrome (AIDS), viral hepatitis B and C and other autoimmune diseases, which are developed mainly as consequences of the disorganization of the immune response. Thus, there is an urgent need for the implementation of holistic studies focused on the molecular mechanisms underlying the phenomenon of anti-viral cellular response. Type 1 diabetes is considered as a virus-provoked disease developed in individuals characterized by specific genetic predisposition. However, the molecular mechanism that governs the onset and progression of the disease remains largely unknown.
The function of all organisms is based on the reliable spatio-temporal and quantitative expression of genes. It is well respected that DNA regulatory elements in combination with transcription factors and the local architecture of chromatic surfaces structure regulatory codes, which determine the gene expression as well as the level of induction of adjacent or distant genes. However, their mechanistic logic has not been fully clarified and is a challenge. The development of new technologies, focusing on the Next Generation Sequencing (NGS), now allows the holistic characterization of regulatory elements and the answer to important questions that remain cloudy for many years like: a) how can regulatory elements, which are located adjacent to or thousands of bases away from the target genes to interact with them, b) the cellular responses are related to specific regions of the genome and c) is there an interaction between the epigenetic status of the nucleus of specific cell types and the likelihood of the emergence / development of a particular disease?
The scientific aim of this diploma thesis entitled “Study of Virus-Induced Gene Expression Programs in Mammalian Cells by Genomics Technology” is to decipher the molecular mechanisms linking viral infection of β pancreatic cells with the development of Type 1 Diabetes through study at the level of the whole genome (genomics) and transcriptomics. Through the study of the mechanisms of gene expression regulation during the anti-viral response, the totality of the regulatory elements that manage/coordinate the cellular response to the development of viral infections is revealed. To achieve this goal, methods of molecular biology, biochemistry, genomics (RNA-seq, DNaseI-seq, ChIP-seq, STARR-seq) and advanced bioinformatics were used, which aim to obtain a complete picture of the molecular phenomena that take place during viral infection of β pancreatic cells.
Keywords:
Type 1 Diabetes (T1D), β-pancreatic cells , Viral-infection, Genomic Technology, Gene Expression Program
