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The Institute of Molecular Genetics (IGM) was founded in September 2000 by the fusion of two CNR centers in Pavia: the Institute of Biochemical and Evolutionary Genetics (IGBE) and the Centre for Histochemical Studies (CSI). In 2007, two further sections in Bologna and Chieti, both previously part of another CNR Institute (ITOI: Institute for organ transplantation and immunology), joined IGM. Thanks to a formal collaboration agreement, the section in Bologna is hosted within the Orthopedic Rizzoli Institute. The remaining section in Chieti, formed by 4 technicians and a single researcher, has been suppressed in 2014 and transformed into a detached branch of the Pavia unit.

In spite of this complex history, the various components of the Institute share common scientific interests with a high level of methodological complementarity. IGM combines investigations on basic cellular processes, renowned at international level, with applied and translational research.

 

IGM is mainly involved in basic research on fundamental biological processes. Four main lines of investigation can be identified, on which converge the activities of groups in Pavia e Bologna:

 

Genome replication, repair and maintenance. DNA replication and repair are at the heart of cell proliferation, evolution and maintenance of genomes. Understanding the molecular mechanisms and regulatory circuits at the basis of these fundamental processes is one of the traditional interests of the institute in Pavia. It is now clear that the integrity of the genome depends on the complex interplays between important biochemical reactions involving the double helix: transcription, replication and repair. How the molecular machineries involved in these processes are coordinated? What are the consequences of a failure in this coordination? Which are the key players in this game? To answer these questions the activities focus on: i) the molecular and cell biology of DNA replication in human and yeast cells; ii) mechanisms of DNA repair and of DNA damage tolerance; iii) the effect of checkpoint activation in response to DNA damage; iv) cell apoptosis, vi) telomere maintenance and senescence. 



 

Hereditary genetic disorders. A significant contribution to address the problem of genome maintenance comes, at least in part, by the genetic, molecular and cell biology analyses of hereditary genetic disorders. Two groups of hereditary disorders are presently studied in the institute: i) genetic diseases due to defects in DNA repair such as xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. The interplays between transcription and DNA repair machineries determine the different clinical manifestations of these disorders. ii) Investigations on musculoskeletal dystrophies, including Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford progeria syndrome, have revealed the importance of nuclear lamina in determining the higher-order organization of chromatin, the chromosome distribution in the interphase nucleus and the epigenetic program. All the aspects deeply impact gene expression and DNA stability. 

 

RNA metabolism is another area of intense research activity. A few CNR researchers investigate the impact of RNA metabolism on genome stability. A failure in the coordination between transcription and DNA replication, in fact, may cause DNA damage. At the same time, transcription and production of short RNAs is required for the assembly of functional DNA repair complexes. It is still an open question whether epigenetic reorganizations resulting from DNA damage may affect gene expression programs by interfering with pre-mRNA processing. Post-transcriptional regulation of gene expression is another field of analysis, in particular, for what concerns the role of splicing factors and alternative splicing programs in tumor progression and in the stress response. Finally, the role of non-coding RNAs in chromatin organization is also investigated.

 

Computational analysis. Traditional interests include the analysis of the genetic structure of the Italian population and of complex genetic diseases. To fulfill the increased need of bioinformatics analysis in modern biology, IGM researchers active in this field have developed the CABGen facility of the institute to interpret genome wide RNA-Seq and Chip-Seq data. Moreover, in collaboration with the Institute of mathematics of CNR in Pavia (IMATI) they develop new tools for the interpretation of gene expression profiles. 

 




Our "young minds"

 

APPLIED AND TRANSLATIONAL RESEARCH

Knowledge obtained through basic science investigations is applied to the development of bioactive compounds and translated into innovative diagnostic and therapeutic strategies for inherited and acquired genetic diseases. These activities include the development of:

  • antiproliferative, antiviral and antibacterial compounds and regulators of apoptosis;
  • therapeutic approaches tested in muscle cells from dystrophic patients and in stem cells models;
  • methods and instrumentations for quantitative auto-fluorescence cytometric analysis of normal and pathological cells aimed at clinical diagnosis (optical biopsy) and to monitor stem cell differentiation programs;
  • protocols to define the role of radiation on the proliferation of stem cells;
  • animal models of complex diseases and genetic disorders.

 

In addition IGM offers a series of services to internal and external users most of which free of charge on a collaboration basis. A detailed description is available at the web site of the Institute (www.igm.cnr.it).

 

The research activity is organized in 7 Research Sections funded by external grants:

  1. Innovative approaches to molecular medicine: from new drugs development to diagnosis.
  2. Hereditary disorders with defects in dna repair. Functional and genetic analysis of factors involved in genome stability.
  3. Artificial chromosomes for gene therapy. Studies on DNA replication in human cells, cell cycle control and proliferation.
  4. Computational Biology.
  5. Degenerative muscular skeletal diseases.
  6. Molecular targets for the control of tumor progression.
  7. Post-transcriptional control of gene expression in response to stress. Factors controlling pre-mRNA splicing in normal and cancer cells.

The Institute is involved in training programs of the University of Pavia and Bologna. As part of this activity, IGM researchers supervise University students during the execution of their experimental work required for the preparation of the master degree theses. In addition, several researchers teach University courses as contract professors. The Institute participates in the organization of courses and seminars of the PhD program in "Genetics, Molecular and Cellular Biology" of the University of Pavia. IGM researchers are faculty members of the same doctorate. PhD students are present also at the IGM unit in Bologna thanks to an agreement with the University of that city.

 

In the last 4 years (2011-2014) IGM researchers published more than 250 scientific articles on international peer-reviewed journals with an average IF:5,2. Remarkably, the list includes several articles on Top scientific journals, including Nature, Science and Cell. This outstanding scientific productivity granted access to numerous national and international competitive funding, which regularly exceeded one million euros per year.

 

IGM researchers have established an extensive network of collaborations with scientists in Italy and abroad. Moreover, they actively collaborate with clinical groups in Italian hospitals, including the Orthopedic Rizzoli Institute in Bologna and the San Matteo hospital in Pavia. It is worth mentioning that, as part of the collaboration with the San Matteo hospital, IGM is establishing a Biobank for the genetic analysis of rheumatoid arthritis.

 

Overall, the Institute of Molecular Genetics is characterized by an excellent level of integration in the national and especially internationally scientific system.

 

 


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