Murine models to test parasite products as cures for Inflammatory Bowel Disease

描述(由申请人提供)：投资于加强曼斯菲尔德博士的小鼠模型活动将导致在了解和治疗由肠道病原体引起的肠道炎症性疾病方面取得进展，并培养兽医进入研究领域。曼斯菲尔德博士于1990年毕业于宾夕法尼亚大学生物医学研究生项目，并于1994年在动物寄生虫研究所完成博士后培训。目前，她已经接受了11年的培训，因此有资格成为一名职业生涯中期的调查员。她的培训和研究生涯都花在开发人和动物传染性肠道疾病的动物模型上。1990-2003年间，她致力于寻找自然发生的空肠弯曲菌和球虫(神经肉孢子虫等)的动物模型。长期目标是将这些转化为老鼠模型。在2002-04年间，她成功地获得了实施这些病原体的小鼠模型的资金，因此，她将比较医学的重点从这些人和动物肠道疾病的大型动物模型转移到了小鼠模型上。最近获得资助和悬而未决的老鼠病理生物学基金记录了这一职业转变。与此同时，她要求免除人口和动物健康诊断中心临床寄生虫学科的行政职责。在她的领导下，案件数量从每年1500件激增至1万英镑，这对研究和指导的时间提出了越来越高的要求。曼斯菲尔德博士寻求职业奖励资金，以加强她在小鼠病理生物学方面的项目，特别是执行由NIH资助的合同“密歇根州立大学微生物学研究单位：食品和水媒综合研究网络”中的项目。这些职业奖基金将帮助建立新的小鼠模型，包括：1)“空肠弯曲菌定植和肠炎的小鼠模型”，以确定空肠弯曲菌和其他肠道细菌刺激肠道慢性炎症的机制；2)“蠕虫介导的炎症性肠病控制”，以确定鞭毛虫特定寄生产物对结肠炎(自发性和致病性)的免疫调节特性。这些小鼠模型将作为第一种模式，测试选定的寄生虫及其分子在下调慢性炎症方面的有效性。曼斯菲尔德博士记录了她在指导研究生方面取得的成功，并试图扩大她对小鼠病理生物学领域的D.V.M.的指导。

DESCRIPTION (provided by applicant): Investing in enhancement of Dr. Mansfield's mouse model activities will result in progress in understanding and treating inflammatory disease of the bowel resulting from enteric pathogens and in fostering veterinarians to enter the research arena. Dr. Mansfield graduated from a V.M.D., Ph.D. program in Biomedical Graduate Studies at the University of Pennsylvania in 1990 and finished postdoctoral training at the Animal Parasite Institute in 1994. Currently, she is 11 years from her training, thus, qualifying as a Mid-Career investigator. Her training and research career were spent developing animal models of human and animal infectious enteric diseases. From 1990-2003, she focused on finding naturally occurring animal models for Campylobacter jejuni and Cyst forming coccidia (Sarcocystis neurona, etc.) with the long-term goal to convert these to mouse models. In 2002-04, she successfully achieved funding to implement mouse models for these pathogens and, thus, shifted her focus within comparative medicine from large animal models of these human and animal enteric diseases to murine models. Recent funded and pending grants on mouse pathobiology document this career shift. Simultaneously, she requested relief from administrative duties running the Clinical Parasitology Section of the Diagnostic Center for Population and Animal Health. Caseloads had burgeoned under her leadership from 1500 to >10,000/year placing increasing demands on time for research and mentoring. Dr. Mansfield seeks Career Award funds to enhance her program in mouse pathobiology especially to pursue projects in the funded NIH contract "Michigan State University Microbiology Research Unit: Food and Waterborne Integrated Research Network". These Career Award funds would enable new mouse models including, 1)"Murine models of C. jejuni colonization and enteritis" to determine mechanisms by which C. jejuni and other enteric bacteria stimulate chronic inflammation in the gut, and 2)"Worm mediated control of inflammatory Bowel Disease" to determine immunomodulatory properties of defined parasitic products from Trichuris on colonic inflammation (spontaneous and pathogenmediated). These mouse models will serve as the first modality for testing select parasites and their molecules for efficacy in down modulating chronic inflammation. Dr. Mansfield has documented success mentoring graduate students and seeks to expand her mentoring of D.V.M.s in mouse pathobiology.