Laboratory for the development of Genetic and Pharmacogenomic Therapy of Thalassemia

(a) development of micro-Chips for gene expression profiling in diagnostic genetics, diagnostic oncology, molecular biology and virology, in studies of genetic of populations, in studies of systematic and applied ecology, in studies on drug production;

(b) development of integrated systems for bioseparation and isolation of materials from medicinal plants and engineered microorganisms;

The objectives in the long term range can be summarized in continuing collaborative effort, Coustom services with small and medium enterprises in the biotechnological field, with National Institutes of Research and Hospitals.

The major scientific objective of the Laboratory is the identification and the characterization of transcription factors that regulate the expression of human globin genes, with particular reference to protein factors acting as "silencers" of transcription.

The practical objective is to design synthetic oligonucleotides (ODN) and peptide-nucleic acids (PNA) able to alter the transcription of globin genes by decoy, antisense and antigéne approaches.

Finally, the Laboratory aims to identify new inducers of erythroid differentiation able to promote the transcription of the globin genes, especially the gamma- and the epsilon-globin genes.

The first phase of the Research Plan is the characterization of transcription factors binding to the promoters of beta-like globin genes, employing a comprehensive analysis of the interactions between nuclear factors and oligonucleotide sequences mimicking globin gene promoter regions.

The second phase is focused on the design and the synthesis of ODN and PNA able to altering in vitro and ex vivo the transcription of the globin genes.

The objective of the third phase is to screen compounds able to interact with the minor groove of DNA with sequence-selectivity, in order to identify molecules able to induce erythroid differentiation.

During the quarter phase we will determine the type of hemoglobin synthetized in the different employed cellular systems and we will study the transcription of the globin genes in erythroid induced cells, in order to identify modifiers of the process of transcription able to acting preferentially on the gamma-globin genes.

During the fifth phase of the research that will be carried on by the ThalLab we will analyse the effects of co-treatment of cells with the synthetized ODN and PNA and other known inducers of erythroid differentiation, such as butyrates, cytosine arabinoside, retinoic acid, 5-azacytidine.

The objective of the sixth phase is the study of "delivery" of the modifiers of the transcription process of transcription using liposomes, microspheres, Biolistic.