Institute for Genetic and Biomedical Research (IRGB)


The Institute of Genetic and Biomedical Research (IRGB), generated by the union of the Institute of Neurogenetics and Neuropharmacology (INN) with the Institute of Population Genetics, consists of the main office in Cagliari and 3 secondary offices in Lanusei (NU ), Sassari and Milan

At the time being, IRGB's leading activity in the main Institute is in Genetics and Molecular Biology.
IRGB's scientific interests focus primarily on monogenetic and polygenetic studies in a population as the Sardinian one, that is genetically homogeneous, and can be assembled in four wide ranges in research:

A. ProgeNIA project, a longitudinal study of a large cohort of Sardinian subjects
1) Study on quantitative traits of specific aspects of aging: mainly Cardiovascular component and Personality component
2) Study on about 300 quantitative traits and phenotypes of general biomedical interest

B. Complex diseases
1) Identification of the genes involved in pathogenesis of Type I Diabetes (TD1)
2) Identification of the genes involved in pathogenesis of Multiple Sclerosis (MS)
3) Next generation sequencing in Sardinian population for the identification of rare variants in MS and TD1
5) Research on genes involved in breast cancer.
6) Identification of the genes involved in the pathogenesis of the most common autoimmune diseases in Sardinia.
7) Functional studies on immunologic diseases.

C. Thalassemia, the most frequent monogenic disease in Sardinia
1) Genotype-phenotype relationship studies.
2) Identification of beta-thalassemia modifier genes.
3) Definition of thalassemia with intact globin gene.
4) Gene therapy.
5) Transcriptional regulation of globin genes.
6) Genes involved in Mesenchimal Staminal cells differentiation.

D. Monogenic diseases
1) Functional on the protein CRLF1 responsible for Crisponi's Syndrom
2) Functional studies on the protein AIRE responsible for autoimmune polyendocrinopathy type I (APECED).
3) Functional studies on FOXL2 gene, crucial for eye and ovary development.
4) Identification of the genes involved in overgrowth and dysmorphic syndromes.

Long term research personnel belonging to the main Institute are 29:
o 1 Senior Researcher,
o 16 Researchers,
o 8 Research Technicians,
o 4 Administrative Assistant.

To these, we must add the temporary employees and many volunteers that permanently cooperate in the Institute's research activity. This is a vast group of people that have been sustaining the long term personnel for years allowing a steady development in the scientific field.

The main Institute of Genetics and Biomedical Research (IRGB) of the CNR has three locations in Sardinia. The three Sardinian sites are located in Cagliari, Lanusei and Pula have been built based on the main research activities and future plans of the Institute and are organized to ensure efficient and integrated distribution of the work.
The Center in Cagliari is the main site of the Institute and it is spread over an area of ~1000 mq and includes the administration of the Institute and four large laboratories well equipped to carry out molecular and cell biology studies. There is also a team of 8 statisticians to perform all the statistical analyses of our Institute.
In the Center in Lanusei, we run the SardiNIA project, a longitudinal study of 6000 volunteers enrolled from 4 nearby villages. The personnel include a recruitment coordinator who contacts the participants, 6 physicians and 4 nurses who perform medical examinations and take samples, 14 biologists who conduct genetic and functional analysis and one bioinformatician who manages the data. This site includes a medical clinic for the visits and sample collection, and five laboratories with more than 14 locations and large instruments (including 2 Affymetrix 7G GeneChip systems and 2 FACS Excalibur Canto 2 Becton Dickinson) where we carry out: blood tests, extraction DNA and RNA, genotyping, cell culture and cytofluorometry
The third site is located in Pula in the Biopark named Sardegna Ricerche where, in close collaboration with the CRS4 (Center for Advanced Studies, Research and Development in Sardinia), we have set up a large infrastructure for massively parallel sequencing, taking also the advantage of an existing major computing facility.
The sequencing laboratory has 3 new Illumina-HighSeq 2000 sequencers, each able to produce up to 300 Gb of raw sequencing data per run and 2 Illumina- Genome Analyzer GA IIx sequencers, able to produce more than 80 Gb of raw data sequencing per run. Attached to the high throughput sequencing lab there is a newly re-tooled multi-teraflop computing centre of CRS4 (currently, 40 Teraflops and a storage capacity of 0.75 PetaBytes) that provides the computational infrastructure necessary to utilize and store the data.

The Milan Unit originates from the activity performed by some researchers in the framework of the Human Genome Project coordinated in the '90s by Prof. Renato Dulbecco. In the last few years, the research activity has developed along the genomics field with particular attention to the applications to human health. Therefore the Milan activity can be characterized as Translational Genomics.

The following themes are pursued:
· Genetics of monogenic diseases, focussing on the pathologies of immune, cardiac and bone systems, as well as on some developmental syndromes such as Cornelia de Lange.

· Genetics of polygenic diseases, with a focus on cardiac pathologies.

· Regenerative medicine. Animal models of bone and heart diseases are used to test novel approaches to cell therapy. In addition, the technologies needed to use induced pluripotent stem cells (iPSC) have been set up.

· Oncology, genome stability and epigenetics that play a fundamental role both in cell differentiation and tumour pathogenesis.

· New antibiotics. This research has recently been implemented, thanks to the collaboration with the private sector, in a joint project sponsored by the Regione Lombardia.

· Role of sarcomeric proteins in cardiac and skeletal muscle function and disease such as dilated and hypertrophic cardiomyopathy, limb-girdle muscular dystrophy, and nemaline myopathy.

· Bioinformatics to integrate and support the study of genes and proteins involved in pathologic processes.

The permanent staff of UOS are 2 Chief of research, 10 Researchers and 2 technicians.

The UOS is located in Milan. This location will be equipped with all the necessary instrumentation to ensure full operations. So far, some research groups work at the LITA Institution in Segrate, while others work at the Istituto Clinico Humanitas (ICH) in Rozzano (Milan), in the framework of a scientific collaboration between the CNR and ICH.

The Sassari branch of the IRGB originated by the confluence of the Cancer Genetics Unit of the CNR of Sassari (which until 2019 belonged to the ICB) with the working group that, in the past, constituted the Institute of Population Genetics. The complete integration of the two research groups has allowed enhancing the activity of the Cancer Genetics unit which is currently focused on precision medicine applied to medical oncology in clinical practice and is based on basic and translational research activities. The scientific activity is aimed to a deeper understanding of pathological mechanisms underlying neoplastic transformation and progression, with the objective of developing both new genetic-molecular biomarkers useful in predicting response and/or resistance to innovative biological therapies - targeted therapy and immunotherapy - or prognostic markers aimed to better management of cancer patients. These in order to achieve a more accurate definition of the different bio-molecular subtypes of neoplastic patients and a better characterization of the inter-and intra-tumor heterogeneity occurring in each neoplastic pathology. Correct classification of cancer patients, on the basis of their personal "molecular pattern", is in fact considered essential for planning the patient's therapeutic strategy, achieving an increasingly positive risk/benefit balance. In this sense, from 2009 to today, the CNR Cancer Genetics Unit of Sassari has been enrolled by an agreement with the Sassari University Hospital (AOU), for carrying out molecular-genetic analyzes on cancer patients' biological samples (tumor tissues and circulating tumor DNA from liquid biopsy), aimed at identifying specific gene mutations, which are predictive of therapeutic response in the oncology field. The samples come from either all oncological facilities in Sardinia or, in the context of specific clinical trials, from the main national reference structures for the diagnosis and treatment of cancer. Furthermore, in recent years, the group has contributed to the constitution of the Diagnostic Therapeutic and Assistance Pathway (PDTA) for melanoma patients at the Sassari AOU, agreeing to the national guidelines of the Medical Oncology Italian Association (AIOM), and other multidisciplinary groups involved in the management of different malignancies as breast cancer (Coordinated Corporate Multidisciplinary Senology; SMAC), lung cancer (Lung Cancer MDT Sassari) and colorectal cancer. In practice, these multidisciplinary groups cooperate for the targeted diagnostic classification of cancer patients, with particular reference to the pathological and molecular-genetic classification of the different types of disease, using the most innovative biotechnologies.

Long term research personnel belonging to the Sassari unit are 17: 1 head of research, 4 IRGB researchers, 3 temporary assigned researchers from ICB-CNR (SS), 4 ICB-CNR (SS) researchers affiliated to IRGB, 1 research technologist, 2 research technicians, 2 administrative assistants. The IRGB staff of the Sassari unit work in close collaboration with various clinical and research facilities in the area (AOU, Hospitals, University Departments of Medicine, etc.). Over the years, the Institute has acquired the most advanced methodologies, complemented by suitable biotechnological equipment and the implementation of skills focused on molecular diagnostics in the biomedical sector.

The Sassari IRGB headquarters is located within the CNR Research Area campus, in the outskirts of Sassari. It occupies the first floor of building G, which consists of about 1300 square meters including the administration offices, the researchers' offices, 4 large well-equipped laboratories for genetics and molecular biology studies, a cell biology and cytogenetics laboratory, a laboratory of proteomics and an educational laboratory, as well as a large library/meeting room.