Transcriptome analysis of the adherent-invasive E. coli phenotype

粘附侵袭性大肠杆菌表型的转录组分析

基本信息

批准号：
9092698
负责人：
Grace N Gathungu
金额：
$ 19.75万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9092698
关键词：
Abdominal Pain Accounting Affect African American Age Anemia Apoptosis Award Bacteria Behavior Biochemistry Bioinformatics Biological Assay Biological Markers Biology Biopsy Biopsy Specimen Caco-2 Cells Cells Child Childhood Clinical Colorado Complex Computer software Crohn&apos s disease Crohn&apos s disease of the ileum Data Detection Diagnosis Diagnostic Disease Disease Management Disease Progression Doctor of Philosophy Enteral Epidemiologic Studies Epithelial Cells Epithelium Escherichia coli Etiology Fistula Funding Future Gastroenterology Gene Expression Genes Genetic Risk Genomics Goals Gram-Negative Bacteria Grant Health Hemorrhagic colitis Hour Human Immune response In Vitro Infection Inflammatory Bowel Diseases Intestines Invaded Knowledge Lesion Mammalian Cell Measures Medical Genetics Medicine Mentors Methodology Microbiology Modeling Molecular Molecular Biology Techniques Molecular Genetics Molecular Probes Mus Mutation New Mexico Ontology Parkinson Disease Pathogenesis Pathway Analysis Pathway interactions Patients Pediatrics Phenotype Phylogenetic Analysis Play Polymerase Chain Reaction Property Prospective Studies RNA RNA Sequence Analysis RNA Sequences Relapse Reporting Research Research Personnel Research Project Grants Research Proposals Reverse Transcription Risk Role Sampling Serotyping Specimen Surgical Management Symptoms Technology Testing Time Tissues Transcript Translational Research Universities Validation Virulence Washington career clinically relevant cost effective disease phenotype genome wide association study gut microbiota ileum macrophage microbiota microorganism interaction mid-career faculty mutant pathogen pediatric patients professor prospective public health relevance rRNA Genes research study response risk variant time use transcriptome transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): This application entitled "Transcriptome analysis of the adherent-invasive E. coli phenotype" is submitted on behalf of Dr. Grace Gathungu in response to PAR-13-074 entitled "Small Grants for New Investigators to Promote Diversity in Health Related Research (R03)." Dr. Gathungu is an African American new investigator board certified in pediatrics and pediatric gastroenterology. The focus of her research is on biomarkers for diagnosis and treatment of inflammatory bowel disease. This R03 award will provide her with the support necessary to: (1) Conduct a focused research project using microbiology and bioinformatics methodology and develop new research technology (2) Establish an independent academic career in IBD research. To achieve these goals, she is guided by mentors: Ellen Li, MD, PhD who is Professor of Medicine at Stony Brook and has a research focus on intestinal microbiota in IBD, Dr. James Bliska a Microbiologist and expert on Bacteria pathogenesis, & Dr. Wei Zhu a Biostatistician. Additional collaborators are: Dr. John Parkinson, Associate Professor of Biochemistry & Molecular and Medical Genetics at the University of Toronto; Dr. Phillip Tarr, Professor of Pediatrics and Molecular Microbiology at Washington University in St. Louis. Dr. Edgar Boedeker, Professor of Medicine at the University of New Mexico; Dr. Daniel Frank, Assistant Professor in the Department of Medicine at the University of Colorado. There remains a critical need to identify more accurate, reliable and reproducible biomarkers to predict disease progression in patients at risk of serious complications such as fistulae, strictures or surgical management of aggressive Crohn's disease (CD). Evidence from 16S ribosomal RNA gene sequencing reveals that the composition of microbiota in the ileum is altered in patients with ilea CD. There are greater proportions of gram negative bacteria including Escherichia coli. It is hypothesized that Adherent Invasive E coli (AIEC) are associated with increased pathogenic potential in patients with ileal CD. AIEC while predominantly of B2 and D phylotypes are a heterogeneous group of serotypes. Currently no molecular probe can distinguish AIEC from non-invasive bacteria. The main hypothesis is that that highly expressed genes (during infection) can be used to detect AIEC in clinical samples and genes important for bacterial E. coli pathogenesis can be identified by metatranscriptome analysis. Dr. Gathungu proposes to characterize the transcriptional profile of AIEC bacteria during invasion of host mammalian cells. She will identify unique transcripts for AIEC bacteria and also define genes that are differentiall regulated in bacteria. As demonstrated in preliminary studies, she will then examine patient fecal and ileal biopsy samples for genomic probes that are AIEC-specific and can reliably be used in prospective epidemiological studies. Dr. Gathungu will use advanced bioinformatics and molecular biology techniques. In future studies and through R01 funding, Dr. Gathungu will apply this knowledge to prospective studies in pediatric patients with CD.

描述（由应用程序提供）：该申请名为“依从性侵入性大肠杆菌表型的转录组分析”，代表Grace Gathungu博士提交，以响应PAR-13-074，标题为“针对“新研究者的小型赠款”，以促进与健康相关研究的多样性（R03）。” Gathungu博士是一家非裔美国人新调查员委员会，获得儿科和小儿胃肠病学认证。她的研究重点是用于诊断和治疗炎症性肠病的生物标志物。该R03奖将为她提供所需的支持：（1）使用微生物学和生物信息学方法论进行重点研究项目，并开发新的研究技术（2）在IBD研究中建立了独立的学术生涯。为了实现这些目标，她受到导师的指导：艾伦·李（Ellen Li），医学博士，博士学位，他是斯托尼·布鲁克（Stony Brook）医学教授，并研究了IBD肠道菌群的研究，詹姆斯·布里斯卡（James Bliska）博士是微生物学家兼细菌发病机理的专家詹姆斯·布里斯卡（James Bliska）博士，＆wei kiostatician a a a a a BioStaticians。其他合作者是：多伦多大学生物化学与分子与医学遗传学副教授John Parkinson博士；圣路易斯华盛顿大学儿科与分子微生物学教授Phillip Tarr博士。新墨西哥大学医学教授Edgar Boedeker博士；科罗拉多大学医学系助理教授Daniel Frank博士。仍然需要确定更准确，可靠和可重复的生物标志物，以预测有严重并发症的患者的疾病进展，例如瘘管，狭窄或对侵略性克罗恩病（CD）的手术治疗。 16S核糖体RNA基因测序的证据表明，ILEA CD患者在回肠中菌群的组成改变了。包括大肠杆菌在内的革兰氏阴性细菌比例更大。假设依从性侵入性E大肠杆菌（AIEC）与回肠CD患者的致病潜力增加有关。 AIEC主要是B2和D系统型是异质的血清型。目前，没有分子探针可以将AIC与非侵入性细菌区分开。主要假设是，高表达基因（在感染期间）可用于检测临床样品中的AIC，并且可以通过元文字分析来鉴定细菌大肠杆菌发病机理重要的基因。 Gathungu博士的提议是在宿主哺乳动物细胞侵袭过程中表征AIEC细菌的转录特征。她将确定针对AIC细菌的独特转录本，并定义细菌中受差异调节的基因。正如初步研究所证明的那样，她将检查患者的粪便和回肠活检样品是否针对特异性的基因组问题，可以可靠地用于前瞻性流行病学研究中。 Gathungu博士将使用先进的生物信息学和分子生物学技术。在未来的研究和通过R01资金中，Gathungu博士将将这些知识应用于儿科患者CD的前瞻性研究。