CELLULAR AND MOLECULAR DETERMINANTS OF BIRTH DEFECTS

这是一份关于出生缺陷分子和细胞机制领域的三名博士前和一名博士后研究培训职位的更新申请。杰斐逊医学院拥有一个领先的出生缺陷研究学术中心。该方法是跨学科的，教师的研究兴趣分为四个重叠的类别：1)介导特定发育转变的细胞信号；2)出生缺陷发病过程中涉及的信号转导事件；3)胚胎发育过程中基因组的结构和功能；4)发育和生殖毒性机制。这项研究项目反映出越来越多的证据表明，出生缺陷是基因和环境相互作用的结果。该提案的目标是培养一流的基础科学家，使他们能够利用现代方法来解决胚胎/胎儿正常和异常发育的分子和细胞机制问题。目前，该领域的研究人员主要在发育生物学和致畸学以外的领域接受培训，而对发育毒理学和分子致畸学专家的需求正在增长。1997年建立了一个新的发育生物学和畸形学硕士项目。虽然硕士和博士课程将并行运作，但该培训补助金将不用于支持硕士水平的学生。对教师的资助是广泛的。总共产生了54项活动赠款，每年的直接费用超过700万美元，还有30项赠款待决，每年的直接费用总额超过300万美元。这些资助在与培训资助相关的教师中得到了很好的分配，反映了广泛的研究课题，涵盖了与神经系统、骨骼系统、上皮组织、肌肉组织、视觉器官等发育相关的机制。机制包括钙转运、信号转导、基因参与特异性缺陷等。研究的环境毒物包括镉、酒精、维生素A和肉毒杆菌毒素。有证据表明，这是分子致畸的主要集中中心。在申请时，托马斯·杰斐逊大学还有其他12项培训补助金（其中3项将于1997年到期）。参与这项资助的教师参与了12个项目中的5个，但很少有重叠。

DESCRIPTION This is a renewal application for three predoctoral and one postdoctoral research training positions in the area of molecular and cellular mechanisms of birth defects. The Jefferson Medical College houses a leading academic center for birth defects research. The approach is interdisciplinary, with faculty research interests falling into four overlapping categories: 1) cellular signals that mediate specific developmental transitions; 2) signal transduction events involved in pathogenesis of birth defects; 3) structure and function of the embryonic genome during development; and 4) mechanisms of developmental and reproductive toxicity. The research program reflects the growing evidence that birth defects are best understood as resulting from the interactions of genes and environment. The objective of the proposal is to train first rate basic scientists so that they are able to utilize contemporary approaches to address questions of molecular and cellular mechanisms of both normal and abnormal development of the embryo/fetus. The field is currently populated by investigators whose primary training is in areas other than developmental biology and teratology, while the need for specialists in developmental toxicology and molecular teratogenesis is growing. A new Masters Program in Developmental Biology and Teratology was established in 1997. Although the M.S. and Ph.D. programs will function in parallel, this training grant will not be used to support Masters-level students. Funding for the faculty is extensive. A total of 54 active grants generated amount to over $7 million annually in direct costs, with 30 grants pending for a total of over $3 million annually in direct costs. These grants are well distributed across the faculty who are affiliated with the training grant and reflect the wide array of research topics covering mechanisms related to developmental of the neural system, the skeletal system, epithelial tissue, muscle tissue, organs of vision, etc. Mechanisms include calcium transport, signal transduction, genes involved in specific defects, etc. Environmental toxicants studied include cadmium, alcohol, vitamin A, and botulinum toxin. Evidence is presented demonstrating that this is a leading focused center for molecular teratogenesis. Twelve other training grants were current at Thomas Jefferson University at the time of application, (three were due to expire in 1997). Faculty involved in this grant are involved in five of the twelve but there is minimal overlap.