Physical modeling of biological systems

点击翻译按钮获取中文摘要

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.