Biology of developmental encephalopathies presenting with infantile spasms

以婴儿痉挛症为表现的发育性脑病的生物学

基本信息

批准号：
8442089
负责人：
Alexander R Paciorkowski
金额：
$ 15.58万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-15 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8442089
关键词：
1 year old Accounting Address Affect Autistic Disorder Bioinformatics Biological Candidate Disease Gene Cerebellar vermis structure Child Childhood Clinical Clinical assessments Cohort Analysis Complex Counseling Custom Data Data Analyses Development Developmental Biology Diagnosis Disease Disease Pathway Dyskinetic syndrome Electroencephalography Encephalopathies Environment Epilepsy Equipment and supply inventories Exons Forebrain Development Future Gene Mutation Genes Genetic Genome Genomics Genotype Goals Hypsarrhythmia Infantile spasms Intellectual functioning disability Intractable Epilepsy Involuntary Movements Knowledge Lead Link Live Birth Medical Genetics Medical Research Mentors Methods Molecular Genetics Morbidity - disease rate Movement Disorders Mutation Neurodevelopmental Deficit Neurodevelopmental Disorder Neurologic Online Systems Outcome Pathogenesis Pathogenicity Pathway Analysis Pathway interactions Pediatric Neurology Pediatrics Phenotype Population Public Health Recruitment Activity Recurrence Research Research Institute Research Personnel Resources Risk Role Science Seeds Sentinel Spasm Structure Subgroup Syndrome Techniques Technology Testing Time Training United States Universities Variant Washington Work base career cohort computer science design disease classification exome sequencing genome sequencing improved insight neurogenetics next generation novel public health relevance research study response skills synaptic function tool trait

项目摘要

DESCRIPTION (provided by applicant): The candidate is fully trained in pediatrics, medical genetics, and child neurology, and this K08 will allow protected time for the consolidation of skills and establishment of his career as an independent researcher in neurogenetics. The candidate's immediate career goals are to integrate phenotyping, molecular genetics, and computer science skills, and establish a research lab the bridges between next-generation genomic sequencing technologies and bioinformatics. Long term career goals are to further the understanding of the key neurodevelopmental disorders affecting large numbers of children in the United States -- epilepsy, autism, and intellectual disability. Inclusive in these goals are th identification of targets for new disease therapies. Environment The proposed work will be performed at the Seattle Children's Research Institute (SCRI), and whole genome sequencing will be completed at the University Of Washington (UW). UW has a longstanding commitment to excellence in medical research, including world-class resources in the Department of Genome Sciences. Research The proposed project addresses infantile spasms - a significant cause of neurologic morbidity in the pediatric population, and for which new therapies are much needed. We believe the best new therapies will arise when underlying mechanisms of pathogenesis are understood. In this proposal we expand on evidence from our group and others that abnormalities of ventral forebrain development and synapse function account for ISS pathogenesis, by designing experiments that integrate cutting-edge genomics with novel bioinformatics approaches. We expect to improve the clinical classification of the disorders presenting with infantile spasms with a new technique of quantitative phenotyping. We expect to identify several new genetic causes of infantile spasms, and to connect those genes to pathways of pathogenesis that can be acted upon in the future development of disease-specific therapies. Finally, we will deploy a publicly available web-based tool that will help in the diagnosis, counseling, and future therapy selection for these disorders.

描述（由申请人提供）：候选人接受过儿科、医学遗传学和儿童神经学方面的全面培训，K08 将为巩固技能和建立其作为神经遗传学独立研究员的职业生涯提供受保护的时间。该候选人的近期职业目标是整合表型分析、分子遗传学和计算机科学技能，并建立一个研究实验室，作为下一代基因组测序技术和生物信息学之间的桥梁。长期职业目标是进一步了解影响美国大量儿童的关键神经发育障碍——癫痫、自闭症和智力障碍。这些目标包括确定新疾病疗法的靶点。环境拟议的工作将在西雅图儿童研究所（SCRI）进行，全基因组测序将在华盛顿大学（UW）完成。威斯康星大学长期致力于卓越的医学研究，包括基因组科学系的世界一流资源。研究拟议的项目旨在解决婴儿痉挛症——这是儿科人群神经系统发病的一个重要原因，因此非常需要新的治疗方法。我们相信，当了解了发病机制的潜在机制后，就会出现最好的新疗法。在本提案中，我们通过设计将尖端基因组学与新颖的生物信息学方法相结合的实验，扩展了我们小组和其他人的证据，即腹侧前脑发育和突触功能的异常解释了 ISS 发病机制。我们期望通过定量表型分析新技术来改进以婴儿痉挛症为表现的疾病的临床分类。我们期望确定婴儿痉挛症的几种新的遗传原因，并将这些基因与发病机制联系起来，以便在未来开发特定疾病的疗法中发挥作用。最后，我们将部署一个公开的基于网络的工具，该工具将有助于这些疾病的诊断、咨询和未来的治疗选择。