Universitą degli studi di Pavia
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Morini research activity
Analysis of the SBDS gene role in Shwachman-Diamond syndrome
The purpose of my PhD in Genetics, Molecular and Cellular Biology is to investigate mechanisms of ionizing radiation action on biological targets, particularly in the study of genetic diseases: In particular, I study the effect of ionizing radiation in lymphocytes derived from patients affected from Shwachman-Diamond syndrome.
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow failure with neutropenia and aplastic anemia, and propensity for myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). It has been estimated that SDS occurs in 1/76000 births.
SDS is caused by mutations in the highly conserved gene, called “Shwachman-Bodian Diamond syndrome” (SBDS), located at chromosome 7q11, which is the only affected gene in SDS currently know. SBDS protein is postulated to function in ribosomal biogenesis, chemotaxis, in cellular stress responses and in DNA metabolism and repair. SBDS depletion causes hypersensitivity to a variety of stress conditions such as endoplasmic reticulum stress and DNA damage, which may explain patient predisposition to MDS/AML.
In this context, will be studied the cellular response to exposure to X rays in lymphocytes derived from Shwachman-Diamond syndrome’s patients.
In the first year of PhD project, some lymphoid cell lines was obtained by EBV-immortalization of lymphocytes. Cell lines were obtained from healthy control, from one patient and from patient’s mother. We are obtaining other cell lines from patients who presents other types of mutations.
We started DNA repair pathways studies. Repair kinetics are studied by COMET assay, by Western Blot analyses of proteins involved in DNA repair and by analyses of γ-H2AX activation after irradiation.
In the first year we have also submitted a research project at the AISS - Italian Association for Shwachman Syndrome. This project has been accepted and has begun in January 2013
The purpose of my PhD in Genetics, Molecular and Cellular Biology is to investigate mechanisms of ionizing radiation action on biological targets, particularly in the study of genetic diseases: In particular, I study the effect of ionizing radiation in lymphocytes derived from patients affected from Shwachman-Diamond syndrome.
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow failure with neutropenia and aplastic anemia, and propensity for myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). It has been estimated that SDS occurs in 1/76000 births.
SDS is caused by mutations in the highly conserved gene, called “Shwachman-Bodian Diamond syndrome” (SBDS), located at chromosome 7q11, which is the only affected gene in SDS currently know. SBDS protein is postulated to function in ribosomal biogenesis, chemotaxis, in cellular stress responses and in DNA metabolism and repair. SBDS depletion causes hypersensitivity to a variety of stress conditions such as endoplasmic reticulum stress and DNA damage, which may explain patient predisposition to MDS/AML.
In this context, will be studied the cellular response to exposure to X rays in lymphocytes derived from Shwachman-Diamond syndrome’s patients.
In the first year of PhD project, some lymphoid cell lines was obtained by EBV-immortalization of lymphocytes. Cell lines were obtained from healthy control, from one patient and from patient’s mother. We are obtaining other cell lines from patients who presents other types of mutations.
We started DNA repair pathways studies. Repair kinetics are studied by COMET assay, by Western Blot analyses of proteins involved in DNA repair and by analyses of γ-H2AX activation after irradiation.
In the first year we have also submitted a research project at the AISS - Italian Association for Shwachman Syndrome. This project has been accepted and has begun in January 2013
