Andrew C. Zelhof - US grants

Animal visual systems vary greatly in morphological form. Development of differences in eye morphology are driven by a need to adapt to the light conditions that an animal experiences and also by the animal's behaviors and survival response repertoire. Understanding the many functional blueprints for designing ways to see and the genes required for these designs will have a direct impact on our basic knowledge regarding the comparative biology of visual systems. Additionally, this work has the potential to deepen our understanding of our own human eyes and also to reveal fundamental design principles for generating artificial systems for light detection and seeing. This study will compare and determine the variations in gene activity that contribute to the differences in morphological form and light sensitivities of eyes in two closely related insect species. The project will integrate research activities with academic programs established at Indiana University that encourage the participation of underrepresented minorities in STEM disciplines. Additionally, it will provide training for teachers to enable them to develop new curriculum and methodology to improve science literacy in elementary and high schools.

The individual rhabdomeres of photoreceptors of apposition compound eyes are organized in a "fused/closed" rhabdom configuration in the ommatidia of the flour beetle, Tribolium, or in an "open/separated" rhabdom configuration in the ommatidia of the fruit fly, Drosophila. The studies in this award will focus on how conserved cellular processes are modified to produce these kinds of adaptive transitions within the constraints of constructing a functional tissue. The three objectives of this study are designed to 1), ascertain the spatial and temporal expression profiles of the Tribolium homologs of the Drosophila proteins known to be required for the generation of open rhabdoms; 2), address the functional consequence of the absence or presence of these proteins in Tribolium; and 3), develop and apply the use of TAL effector nucleases (TALENs) to generate null mutations in Tribolium with the goal of testing genetic relationships between the genes investigated in objectives 1 and 2. Overall this investigation will provide fundamental insights into how conserved cellular mechanisms are adapted, modified, or eliminated to generate novel and adaptive morphological organizations.

Project Summary: The Drosophila Genomics Resource Center (DGRC) supports the international community of scientists utilizing Drosophila melanogaster for biomedical research. The mission of the DGRC is to 1) provide broad access to genomics resources by acquiring, archiving, curating, and distributing genomics resources including clones, vectors, and cell lines; 2) facilitate effective use of these genomics resources by providing guidance and support; and 3) improve the genomics resources and protocols available for Drosophila research. By preserving vital research materials and distributing them efficiently, the DGRC assures economical access and enhances scientific rigor and reproducibility. The first aim of this proposal is to continue and strengthen the successful DGRC programs for acquiring, distributing genomics resources and facilitating their effective use. This will include augmenting and updating data management systems, the web interface and user support, as well as continuing the effective cost recovery program. The goal is to maximize the long-term viability of the DGRC and its benefits to users and the NIH. The second aim is to increase the utility of Drosophila as a model system by generating new resources through four projects: 1) surveying the transfection and CRISPR/Cas9 efficiency of gene tagging across modENCODE cell lines, 2) generating a universal CRISPR/Cas9 based transfection toolkit for the insertion of constructs and the subsequent ability to generate stable transformants in any Drosophila cell line, 3) establishing a neuroblast cell line as a model for stem cell biology, and 4) creating new metabolic sensors for characterizing physiological processes in cell lines and Drosophila tissues.

Project Summary: The Drosophila Genomics Resource Center (DGRC) supports the international community of scientists utilizing Drosophila melanogaster for biomedical research. The mission of the DGRC is to 1) provide broad access to genomics resources by acquiring, archiving, curating, and distributing genomics resources including clones, vectors, and cell lines; 2) facilitate effective use of these genomics resources by providing guidance and support; and 3) improve the genomics resources and protocols available for Drosophila research. By preserving vital research materials and distributing them efficiently, the DGRC assures economical access and enhances scientific rigor and reproducibility. The first aim of this proposal is to continue and strengthen the successful DGRC programs for acquiring, distributing genomics resources and facilitating their effective use. This will include augmenting and updating data management systems, the web interface and user support, as well as continuing the effective cost recovery program. The goal is to maximize the long-term viability of the DGRC and its benefits to users and the NIH. The second aim is to increase the utility of Drosophila as a model system by generating new resources through four projects: 1) surveying the transfection and CRISPR/Cas9 efficiency of gene tagging across modENCODE cell lines, 2) generating a universal CRISPR/Cas9 based transfection toolkit for the insertion of constructs and the subsequent ability to generate stable transformants in any Drosophila cell line, 3) establishing a neuroblast cell line as a model for stem cell biology, and 4) creating new metabolic sensors for characterizing physiological processes in cell lines and Drosophila tissues.