Physical modeling of biological systems

我们与来自（1）物理生物学计划，NICHD，（2）分子医学分支，NIDDK，和（3）疟疾和媒介研究实验室，NIAID的研究人员组成的联盟，正在研究人类血红蛋白异常对疟原虫繁殖适应性的影响。我们已经通过实验证明，疟疾寄生虫在地中海贫血患者的红细胞中以较低的速率繁殖。我们已经表明，理论计算强烈表明，降低寄生虫繁殖率是保护疟疾患者，允许更有效的宿主免疫反应的寄生虫。关于这项工作的同行评议论文已经发表，并在2014年6月的戈登研究会议上发表了关于这项工作的演讲。 与福格蒂国际中心国际流行病学和人口研究部的一名研究人员以及访问NIAID疟疾和病媒研究实验室的芝加哥洛约拉大学的一位教授一起，我们开发了一个疟疾寄生虫传播形式配子体种群动力学的现象学模型。我们发现，对于相同的攻击和清除目标的能力，宿主对未成熟的非传染性配子体的免疫反应比直接对成熟的传染性形式的免疫反应更能影响传播。关于这项工作的同行评议论文已经发表。2013年11月，在美国热带医学与卫生学会年会上展示了有关这项工作的海报。 与来自（1）国家精神卫生研究所神经毒理学实验室，（2）物理生物学计划（NICHD），（3）国家癌症研究所病理学实验室，（4）信息技术中心计算生物科学部计算生物科学与工程实验室，（5）生物医学工程和物理科学共享资源，国家生物医学成像和生物工程研究所，我们模拟了在激活表达显微切割操作中发生的热和流体传输。这是一种提取大量细胞的方法，其中正常表达的蛋白质用吸光染料染色。在暴露于光下时，加热的染色剂熔化结合到组织上的聚合物膜，从而允许细胞成分的拾取。工程开发已接近该方法可用于病理学实验室的程度，NIH技术转让办公室正在与潜在的商业开发商进行谈判。 本课题组与中国科学院基因调控与发育研究室合作，对果蝇视网膜神经元生长进行了统计学和拓扑学分析。我们已经发现，神经元上激活素复合物受体的破坏可以极大地改变树突分支的模式。此外，我们还发现，树枝状分支和终止不是简单的泊松过程。关于这项工作的同行审查论文已经发表，正在编写第二篇文章供同行审查。 与来自（1）NCI细胞生物学实验室和（2）CIT计算生物科学部计算生物科学与工程实验室和（3）国家生物医学成像和生物工程研究所生物医学工程和物理科学共享资源的研究人员组成的联盟，我们做了一个生物反应器的工程设计，用于在一个3D矩阵中生长细胞，该矩阵具有用于输送氧气的毛细血管样组件。描述这种装置的同行评审论文已经发表，并提交了专利申请。 我们与NICHD细胞调节和代谢项目的一名研究人员一起，正在研究逆转录转座子插入真核生物染色体的频率。一个专门设计的核苷酸序列库连接到逆转录转座子上，允许对热点周围的基因组模式进行统计分析，热点是染色体上插入发生率高的位置。关于这项工作的同行评议论文已经发表，正在编写第二篇论文供同行评议。

With a consortium of investigators from (1) Program in Physical Biology, NICHD, (2) Molecular Medicine Branch, NIDDK, and (3) Laboratory of Malaria and Vector Research, NIAID, we are studying the affects of human hemoglobin abnormalities on the reproductive fitness of malaria parasites. We have demonstrated experimentally that malaria parasites reproduce at a lower rate in erythrocytes from patients with Thalassemia anemia. We have shown that theoretical calculations suggests strongly to that lowering the rate of parasite reproduction is protective in malaria patients by allowing a more effective host immune response to the parasite. A peer-reviewed paper about this work has been published, and a talk about this work was given in June 2014 at the Gordon Research Conference on the Biology of Host-Parasite Interactions. With an investigator in the Division of International Epidemiology and Population Studies, Fogarty International Center, and with a professor from Loyola University Chicago visiting the Laboratory of Malaria and Vector Research, NIAID, we have developed a phenomenological model of population dynamics of the transmissible form of the malaria parasite, the gametocytes. We showed that for the same ability to attack and remove targets, host immune responses against the immature, non-transmissible gametocytes would affect transmission more than immune responses directly against the mature, transmissible forms. A peer-reviewed paper about this work has been published. A poster about this work was presented in November 2013 at the annual meeting of the American Society of Tropical Medicine and Hygiene. With a consortium of investigators from (1) Laboratory of Neurotoxicology, National Institute of Mental Health, (2) Program in Physical Biology, (NICHD), (3) Laboratory of Pathology, National Cancer Institute, (4) Computational Bioscience and Engineering Laboratory, Division of Computational Bioscience, Center for Information Technology, (5) Biomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, we modeled the thermal and fluid transport that occur in the operation of activated expression microdissection. This is a method of extracting large number of cells in which a normally expressed protein is stained with a light-absorbing dye. At exposure to light, the heated stain melts a polymer film that binds to tissue, allowing for pickup of cellular components. The engineering development is nearing the point where the method can be utilized in pathology laboratories, and the NIH Office of Technology Transfer is in negotiations with potential commercial developers. With an investigator in Laboratory of Gene Regulating and Development, NICHD, we are working on statistical and topological analysis of retinal neurons growth in Drosophila. We have found that disruption of receptors on neurons of the activin complex can greatly change the pattern of dendritic branching. In addition, we have found that dendritic branching and termination are not simple Poisson processes. A peer-reviewed paper about this work has been published, and a second article is being prepared for peer-review. With a consortium of investigators from (1) Laboratory of Cell Biology, NCI, and (2) Computational Bioscience and Engineering Laboratory, Division of Computational Bioscience, CIT, and (3) Biomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, we did engineering design of a bioreactor for growing cells in a 3D matrix with capillary-like components for delivery of oxygen. A peer-reviewed paper describing this apparatus has been published, and a patent application submitted. With a researcher in the Program in Cellular Regulation and Metabolism, NICHD, we are studying the frequency at which retrotransposons insert themselves into eukaryote chromosomes. A library of specially engineered nucleotide sequences are attached to the retrotransposons, allowing for a statistical analysis of genome patterns around hot spots, positions on chromosomes where insertion occur at a high rate. A peer-reviewed paper about this work has been published, and a second paper article is being prepared for peer-review.