Physical modeling of biological systems

我们与细胞调节和代谢项目的高级研究员NICHD一起，正在研究反转录转座子插入真核细胞染色体的机制和速度。一个特殊设计的核苷酸序列文库被连接到反转录转座子上，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频率较高的位置。2014年发表了一篇同行评议的论文，第二篇同行评议的论文刚刚被接受发表。第二篇论文收录了美国国立卫生研究院生物化学和分子生物学实验室的一名研究人员所做的贡献。 我们与NICHD基因调控与发育实验室的一名首席研究员以及CIT计算生物科学部生物医学成像研究服务部的成员一起，致力于对果蝇视网膜神经元生长的统计和拓扑分析。我们发现，破坏神经元上激活素复合体的受体可以极大地改变树突状分支的模式。此外，我们还发现树枝的分枝和终止不是简单的泊松过程。2014年发表了一篇关于这项工作的同行评议论文，目前正在编写第二篇文章供同行评议。 与基础神经科学计划的高级研究员NINDS以及CIT计算生物科学部生物医学成像研究服务部的成员一起，我们正在研究果蝇胞体神经元轴突随着生物发育成熟而生长的动力学。我们对引导神经元轴突达到其最终目标的机制特别感兴趣。 与Fogarty国际中心国际流行病学和人口研究部的一名高级科学家一起，我们开发了疟疾寄生虫传播形式的种群动力学的现象学模型，该模型包含宿主免疫反应和宿主针对寄生虫的红细胞生成反应。在过去的几年里，该项目已经发表了几篇同行评议的文章，我们的工作是修改该模型，以包括关于保护性血红蛋白疾病和宿主免疫系统缺陷的新知识。 与来自国家生物医学成像和生物工程研究所(1)物理生物学项目(NICHD)、(2)计算生物科学和工程实验室、信息技术中心计算生物科学部和(3)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，我们对激活表达微切割操作中发生的热和流体传输进行了建模。这是一种提取大量细胞的方法，在这种方法中，正常表达的蛋白质被光吸收染料染色。在光照下，加热的污渍会熔化一层与组织结合的聚合物薄膜，从而使细胞成分得以拾取。工程开发接近于将该方法用于病理实验室，美国国立卫生研究院技术转移办公室正在与潜在的商业开发商进行谈判。

With a Senior Investigator in the Program in Cellular Regulation and Metabolism, NICHD, we are studying the mechanisms and rate by 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 was published in 2014, and a second peer-reviewed paper article has just been accepted for publication. This second paper included contributions from a PI in the Laboratory of Biochemistry and Molecular Biology, NCI. With an principal investigator in Laboratory of Gene Regulating and Development, NICHD, and with members of the Biomedical Imaging Research Services Section of the Division of Computational Bioscience, CIT, we are working on statistical and topological analysis of retinal neurons growth in Drosophila. We have found that disruption of receptors on neurons for 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 was published in 2014, and a second article is being prepared for peer-review. With a Senior Investigator in the Basic Neuroscience Program, NINDS, and with members of the Biomedical Imaging Research Services Section of the Division of Computational Bioscience, CIT, we are studying the dynamics of the growth of soma neuron axons in soma of Drosophila as the creatures develop into their mature forms. We are particular interested in mechanisms that guide neurons axons to their ultimate targets. With an Senior Scientist in the Division of International Epidemiology and Population Studies, Fogarty International Center, we have developed a phenomenological model of population dynamics of the transmissible form of the malaria parasite that incorporate host immune responses and host erythropoietic responses against the parasites. Several peer-reviewed articles from this project have appeared in past years, and our work is on going to adapt the model to include new knowledge concerning protective hemoglobinapathies and host immune system deficients. With a consortium of investigators from the (1) Program in Physical Biology, (NICHD), (2) Computational Bioscience and Engineering Laboratory, Division of Computational Bioscience, Center for Information Technology, and (3) 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.