Area:
Neuroscience Biology, Molecular Biology
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High-probability grants
According to our matching algorithm, Edward C. Gilmore is the likely recipient of the following grants.
| Years |
Recipients |
Code |
Title / Keywords |
Matching
score |
| 2007 — 2011 |
Gilmore, Edward Charles |
K08Activity Code Description:
To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Dna Breaks and Repair During Neuronal Development @ Children's Hospital Boston
[unreadable] DESCRIPTION (provided by applicant): Mental retardation is a devastating condition often associated with abnormal neuronal development. Although, approximately 300 genes have been associated mental retardation, most cases have no known cause. We have identified a new genetic syndrome of mental retardation, severe microcephaly, disabling seizures and behavioral problems called microcephaly with seizures (MCSZ). MCSZ results from disruption in the DNA repair gene 5' polynucleotide kinase 3 phosphatase (PNKP). We propose to analyze the role of PNKP in humans and mice, as well as DNA damage in neuronal development. 1) We propose to characterize abnormalities in DNA repair in lymphocytes from patients with MCSZ. We hypothesize that lymphocytes from MCSZ patients will have abnormal DNA repair caused by multiple types of DNA damaging agents. We also hypothesize that patients with less severe symptoms of mental retardation, microcephaly or seizures will also have PNKP mutations. We will attempt to identify such patients. 2) We propose to characterize PNKP's requirement for brain development by generating PNKP deficient mice. We hypothesize that the mice will have neuronal cell death during development. We will determine if they have abnormalities predisposing for seizures. We will also characterize PNKP deficient mice for other diseases, such as cancer. 3) We hypothesize that DNA breaks are common in both human and mouse neuronal development. We will characterize the presence and timing of these DNA breaks during human and mouse cerebral cortical development. In addition, we will attempt to identify genomic regions associated with DNA breaks by multiple and novel methods. This proposal will provide the first insight into a novel and devastating neurological disease, MCSZ. While this disease has some similarities to other disease that cause autosomal recessive microcephaly and other DNA repair abnormalities, it also has unique features that make this disease significantly different than these diseases. For these reasons, we hope our analysis may provide insight into the development of mental retardation and seizures in general. In addition, we will attempt to uncover why the developing brain is susceptible to DNA breaks in general with the eventual hope of identifying any benefit these breaks provide the organism. [unreadable] [unreadable] [unreadable]
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