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（由申请人提供）：本申请题为“粘附侵袭性大肠杆菌表型的转录组分析”，代表 Grace Gathungu 博士提交，以回应题为“为新研究者促进多样性提供小额资助”的 PAR-13-074健康相关研究 (R03)。”Gathungu 博士是一位非裔美国新研究者，获得儿科和儿科胃肠病学认证。她的研究重点是该 R03 奖项将为她提供必要的支持，以：（1）利用微生物学和生物信息学方法开展重点研究项目并开发新的研究技术（2）在 IBD 领域建立独立的学术生涯。为了实现这些目标，她得到了导师的指导：Ellen Li 博士（石溪大学医学教授，研究重点是 IBD 肠道微生物群）、微生物学家和专家 James Bliska 博士。其他合作者包括：多伦多大学生物化学与分子和医学遗传学副教授 John Parkinson 博士；华盛顿大学儿科和分子微生物学教授 Phillip Tarr 博士。圣路易斯大学医学教授埃德加·博德克（Edgar Boedeker）博士；科罗拉多大学医学系助理教授丹尼尔·弗兰克（Daniel Frank）博士仍然存在批评。需要确定更准确、可靠和可重复的生物标志物来预测有严重并发症风险的患者的疾病进展，例如瘘管、狭窄或侵袭性克罗恩病 (CD) 的手术治疗。来自 16S 核糖体 RNA 基因测序的证据表明，微生物群的组成。回肠 CD 患者的回肠中存在较大比例的革兰氏阴性菌，包括大肠杆菌。 (AIEC) 与回肠 AIEC 患者的致病潜力增加有关，而 B2 和 D 系统型主要是一组异质血清型。主要假设是，AIEC 与非侵袭性细菌高度不同。表达的基因（感染期间）可用于检测临床样本中的 AIEC，并且可通过元转录组分析来鉴定对细菌大肠杆菌发病机制重要的基因。Gathungu 博士建议表征转录。她将鉴定 AIEC 细菌在入侵宿主哺乳动物细胞过程中的独特转录本，并定义细菌中差异调节的基因，如初步研究所示，然后她将检查患者粪便和回肠活检样本中的基因组探针。 Gathungu 博士将在未来的研究中使用先进的生物信息学和分子生物学技术，并通过 R01 资助进行应用。这些知识可用于对儿科 CD 患者进行前瞻性研究。