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.

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Budget End
Support Year
3
Fiscal Year
2015
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Name
Computer Research and Technology
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Ting, Chun-Yuan; McQueen, Philip G; Pandya, Nishith et al. (2017) Analyzing Dendritic Morphology in Columns and Layers. J Vis Exp :
Luo, Jiangnan; McQueen, Philip G; Shi, Bo et al. (2016) Wiring dendrites in layers and columns. J Neurogenet 30:69-79
Hickey, Anthony; Esnault, Caroline; Majumdar, Anasuya et al. (2015) Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces pombe. Genetics 201:905-24
Glushakova, Svetlana; Balaban, Amanda; McQueen, Philip G et al. (2014) Hemoglobinopathic erythrocytes affect the intraerythrocytic multiplication of Plasmodium falciparum in vitro. J Infect Dis 210:1100-9
Chatterjee, Atreyi Ghatak; Esnault, Caroline; Guo, Yabin et al. (2014) Serial number tagging reveals a prominent sequence preference of retrotransposon integration. Nucleic Acids Res 42:8449-60
Ting, Chun-Yuan; McQueen, Philip G; Pandya, Nishith et al. (2014) Photoreceptor-derived activin promotes dendritic termination and restricts the receptive fields of first-order interneurons in Drosophila. Neuron 81:830-846
Jaeger, Ashley A; Das, Chandan K; Morgan, Nicole Y et al. (2013) Microfabricated polymeric vessel mimetics for 3-D cancer cell culture. Biomaterials 34:8301-13
McQueen, Philip G; Williamson, Kim C; McKenzie, F Ellis (2013) Host immune constraints on malaria transmission: insights from population biology of within-host parasites. Malar J 12:206
Billig, Erica M W; McQueen, Philip G; McKenzie, F Ellis (2012) Foetal haemoglobin and the dynamics of paediatric malaria. Malar J 11:396