Grant Number: P40OD010949

Research Emphasis/Objectives

The Drosophila Genomics Resource Center (DGRC) supports an international community of scientists utilizing Drosophila melanogaster for biomedical research. The mission of the DGRC is to (1) provide the research community broad access to genomics resources by acquiring, archiving, curating, and distributing genomics resources, including, clones, vectors, and cell lines; (2) facilitate the effective use of the genomics resources by providing guidelines and support; and (3) improve the genomics resources and protocols available to the research community. By balancing the process of archiving and curating material, efficient distribution, and economical access, the effort of the DGRC increases both the scientific rigor and reproducibility of the collective work of the research community and protects against the loss of vital materials. 

Services Provided

• Collecting and distributing cDNA clones and vectors
• Collecting and distributing Drosophila cell lines
• Developing and improving cell line/genomics technologies for use in Drosophila
• Assisting the research community in the use of these resources

Contact Information

Drosophila Genomics Resource Center (DGRC)
1001 E. Third St.
Bloomington, IN 47405
dgrc.bio.indiana.edu/Home

Principal Investigators

Andrew C. Zelhof, Ph.D.
Phone: 812-855-0294
azelhof@indiana.edu

Co-Principal Investigators

Kris Klueg, Ph.D.
Phone: 812-855-5510
dgrc@indiana.edu

Arthur Luhur, Ph.D.
Phone: 812-855-5510
dgrc@indiana.edu

Daniel Mariyappa
Phone: 812-855-5510
dgrc@indiana.edu

Grant Number: R24OD023046

Research Objectives

This award supports the creation and dissemination of research tools that will enable biologists to elucidate the genomic control of embryogenesis through the experimental dissection of developmental gene regulatory networks in sea urchins and other echinoderms.

Services Provided

(1) Production of recombineered bacterial artificial chromosomes (BACs) that encode fluorescent reporter proteins under the cis-regulatory control of endogenous echinoderm genes. (2) Digital analysis of gene expression by means of NanoString technology. (3) Resources for the genome-wide identification of cis-regulatory modules (CRMs). (4) Photoactivatable morpholino antisense oligo nucleotides for conditional (spatially and temporally regulated) gene knockdowns.

Contact Information

Resource for Developmental Regulatory Genomics
Dr. Charles Ettensohn
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
echinobase.org

Co-Principal Investigators

Dr. Charles Ettensohn
Phone: 412-268-5849
Fax: 412-268-7129
ettensohn@cmu.edu

Dr. Veronica Hinman
Phone: 412-268-9348
Fax: 412-268-7129
veronica@cmu.edu

Grant Number: R24OD019847

Research Emphasis/Objectives

All diseases result from disturbances at the cellular level, and functional analyses of human diseases increasingly rely on cell biological studies to uncover root causes of disease. Importantly, cell-level analyses are revealing that many diseases affect the function and/or morphology of organelles, signal transduction, homeostasis, or cell growth. For example, cancer is frequently associated with nucleolar hypertrophy and/or altered signaling, neurodegenerative diseases are associated with changes in mitochondria, and many myopathies are associated with lysosomal disorders. These types of defects are readily assayed in cultured cells, given the right cell types, markers, and tools. The availability of resources that enable systematic cell biological analyses in various cell types are critical to assess the functions of genes implicated in diseases. Analysis of the Drosophila genome sequence has revealed striking conservation among fly and human genes. Drosophila orthologs have been identified for about two-thirds of human disease genes, and all major signal transduction pathways are conserved between flies and humans. The full potential of Drosophila cell lines, particularly for disease-related studies, has not yet been realized, as the repertoire of cell lines is limited, as is the availability of live-cell reporters and mutant cell lines. To overcome these unmet needs, we are using exciting new advances to generate reagents that will enable the community to fully exploit the power of Drosophila cell lines to address disease-related questions. The goals of this work are to (1) generate new cell lines derived from specific Drosophila cell types, using a technique pioneered by Dr. Simcox; (2) use CRISPR-Cas9 genome engineering to develop a resource of cell lines expressing fluorescent markers that "light up" specific subcellular components, such as the nucleus or mitochondria; and (3) use CRISPR-Cas9 gene editing to generate "knockout" cell lines for cell-based screens. For this last aim, we are focusing on knockout of fly orthologs of tumor suppressor genes to facilitate synthetic lethal screens, which have the potential to identify new targets for cancer treatment.

Services Provided

We build CRISPR-modified Drosophila cell lines and derive new Drosophila cell lines using a tissue-specific RasV12 approach. These cell line resources are shared with the Drosophila Genomics Resource Center (DGRC) for distribution to the community.

Contact Information

Stephanie Mohr, Ph.D.
Director of Drosophila RNAi Screening Center/TRiP Functional Genomics Resources
Harvard Medical School
New Research Building, Room 336
77 Avenue Louis Pasteur
Boston, MA 02115
stephanie_mohr@hms.harvard.edu

Resource name: Drosophila RNAi Screening Center (DRSC) modified cell line collection at DRSC/TRiP Functional Genomics Resources
Website (CRISPR-modified cell line information at the DRSC): fgr.hms.harvard.edu/crispr-modified-cell-lines
Website (new and CRISPR-modified cell line distribution by DGRC): dgrc.bio.indiana.edu/cells/Catalog

Co-Principal Investigators

Norbert Perrimon, Ph.D.
Harvard Medical School
Phone: 617-432-7672
perrimon@genetics.med.harvard.edu

Amanda Simcox, Ph.D.
Ohio State University
Phone: 614-292-8857
simcox.1@osu.edu

Other/Resource Contacts

Stephanie Mohr, Ph.D.
Co-Investigator and Director of DRSC/TRiP Functional Genomics
stephanie_mohr@hms.harvard.edu

Grant Number: R24OD021997

Research Emphasis/Objectives

Drosophila has been used extensively to model human diseases associated with reduction or loss of gene function. Diseases associated with gene amplification, microduplication, or other changes resulting in over-expression have been more challenging to model. Over-expression models would be extremely valuable, as they would, for example, provide a system for relatively rapid identification of genetic or chemical modifiers of associated phenotypes. Fusion of Cas9 protein to transcriptional activators, in combination with appropriate small guide RNAs (sgRNAs) upstream of a coding sequence, provides a straightforward, effective, and targeted technology for over-expressing genes in Drosophila tissues (CRISPR-OE). This method gives us a unique opportunity to build a much-needed resource to study phenotypes associated with gene over-expression in vivo. The goals of this project are to (1) use our existing Transgenic RNAi Project (TRiP) RNAi and CRISPR sgRNA fly stock production pipeline to develop CRISPR-OE fly models for diseases associated with amplification or duplication; (2) develop CRISPR-OE flies for rate-limiting enzymes, as this information can help elucidate the impact of perturbing metabolic pathways associated with health and disease; and (3) perform an initial characterization of the CRISPR-OE fly stocks, adding to their value for research studies by others. With regard to the first goal, our focus will be on developing fly stock models for genes amplified in cancers or duplicated in syndromes associated with chromosomal microduplications.

Services Provided

Production of fly stocks with single guide RNAs (sgRNAs) targeting upstream gene regions, such that they are useful for CRISPR over-expression (CRISPR-OE) using the VPR or SAM activation systems. Immediately following production and validation, the fly stocks are shared with the Bloomington Drosophila Stock Center (BDSC) for distribution to the community.

Contact Information

Jonathan Zirin, Ph.D.
Assistant Director of Drosophila RNAi Screening Center (DRSC)/TRiP Functional Genomics Resources
Harvard Medical School
​New Research Building, Room 336
77 Avenue Louis Pasteur
Boston, MA 02115
jzirin@genetics.med.harvard.edu

Resource name: Transgenic RNAi Project (TRiP) CRISPR over-expression (TRiP-CRISPR-OE) platform at the DRSC/TRiP Functional Genomics Resources
Fly stock information: fgr.hms.harvard.edu/crispr-fly-stocks-and-vectors
Search and nominate genes for fly stock production: www.flyrnai.org/tools/grna_tracker/web
Fly stock distribution by BDSC: bdsc.indiana.edu/stocks/genome_editing/sgrna.html

Principal Investigator

Norbert Perrimon
Harvard Medical School
Phone: 617-432-7672
perrimon@genetics.med.harvard.edu

Other/Resource Contacts

Jonathan Zirin, Ph.D.
Assistant Director of DRSC/TRiP Functional Genomics
jzirin@genetics.med.harvard.edu

Grant Number: P40OD018537

Research Emphasis/Objectives

The Bloomington Drosophila Stock Center at Indiana University collects, curates, maintains, and distributes strains of Drosophila melanogaster. The primary goal of the center is to provide the Drosophila research community access to a collection of genetically defined strains that standardize and fuel research discoveries. Emphasis is placed on providing strains with significant experimental value to a broad range of investigations. These include marker, reporter, balancer, and mapping strains; strains with mutant alleles; strains with chromosomal deficiencies and duplications; engineered strains for somatic and germline clonal analysis; RNAi strains for targeted gene knockdown; guide RNA strains for CRISPR-based gene knockout and Cas9-dependent gene expression; GAL4, UAS, QF, QUAS, LexA, and LexAop strains for targeted gene expression; engineered strains for high-efficiency transgenesis, including phiC31-mediated recombination; fully sequenced wild-type strains; and strains for modeling human disease- and health-related processes, such as those expressing human genes.

Services Provided

Approximately 76,000 fly strains are currently available to our user base of over 7,400 Drosophila researchers at nearly 2,000 institutions. To improve their value and usefulness, each strain is curated with relevant information, such as provenance, associated genes, and the potential uses of its genetic components. Users can access this information using robust search tools on the website or by browsing over 400 webpages detailing individual sets of stocks, with particular emphasis placed on human disease applications (see bdsc.indiana.edu/stocks/hd/index.html). The BDSC cross-references extensively with FlyBase, the primary access point for information on Drosophila, allowing scientists to seamlessly transition between the two websites when planning experiments. Stock Center scientists are available to answer questions about strains, Drosophila genetics, experimental design, and use of the website.

Contact Information

Bloomington Drosophila Stock Center
Department of Biology
Indiana University
1001 East 3rd Street
Bloomington, IN 47405-7005
Bloomington Drosophila Stock Center at Indiana University

Co-Principal Investigators

Kevin R. Cook, Ph.D.
Phone: 812-856-1213
kercook@indiana.edu

Annette L. Parks, Ph.D.
Phone: 812-855-5783
anlparks@indiana.edu

Xiangzhong Zheng, Ph.D.
Phone: 812-856-1213
samzheng@iu.edu

Cale Whitworth, Ph.D.
Phone: 812-855-5782
calewhit@iu.edu

Thomas C. Kaufman, Ph.D.
Phone: 812-855-3033
kaufman@indiana.edu

Grant Number: P40OD010952

Research Emphasis/Objectives

The National Resource for Aplysia provides investigators with laboratory-reared California sea hares, Aplysia californica, of known age and standardized environmental background at all stages of development, from eggs to mature adults, as well as red algae to feed animals.

The primary goals of the Resource are to optimize and standardize Aplysia used by NIH investigators and to expand the uses of the Aplysia model system. This includes a health monitoring program and studies to optimize larval rearing and diet at all life stages. Current research programs focus on investigating behavioral, neurophysiological, and transcriptomic changes associated with aging and onset of senescence. Landmarks of aging created through these studies are used to produce quantifiably aged animals for researchers. Studies also are ongoing to determine the effects of exercise on learning through the lifespan, as well as resistance to prolonged hypoxia normally encountered by these intertidal animals.

Aplysia is an important educational tool, as well. The Resource regularly provides animals for use in hands-on neurobiology labs, from high school through graduate-level courses. 

Services Provided

Sibling animals of known ages and stages are available to investigators throughout the year. On request, Aplysia and its food (red algae) are shipped via FedEx overnight priority. Special cohorts, procedures, or manipulations of animal groups can be arranged by contacting the Resource.

The colony currently contains more than 10,000 laboratory-reared animals at various life stages. All animals are produced from field-collected brood stock or field-collected animals bred to lab-reared brood stock, monitored for health, and randomly tested for behavioral responses prior to shipping.

Facility staff will provide advice on setting up marine aquarium facilities for short-term holding of Aplysia shipped from the Resource.

Guest Investigators and Graduate Students

Guest investigators and graduate students interested in studies of life history, culture, genetics, and neurophysiology are encouraged to inquire about conducting studies at the Resource. Selection will be based on the relevance of the proposed study and the availability of resources to meet individual needs.

Contact Information

National Resource for Aplysia
Rosenstiel School of Marine and Atmospheric Science
University of Miami
4600 Rickenbacker Causeway
Miami, FL 33149
National Resource for Aplysia

Principal Investigator

Michael C. Schmale, Ph.D.
mschmale@rsmas.miami.edu

Scientific Director

Lynne A. Fieber, Ph.D.
lfieber@rsmas.miami.edu

Resource Manager

Phillip Gillette
Phone: 305-421-4941
pgillette@rsmas.miami.edu

Grant Number: P40OD010440

Research Emphasis/Objectives

The Caenorhabditis Genetics Center (CGC) acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans. The goal is to maintain a null mutation for every gene, as well as strains providing useful genetic and molecular tools. Strains selected for inclusion in the CGC include chromosome rearrangements (balancers) and deficiencies, tagged endogenous loci, and tools for sex-, cell-, and temporal-specific gene expression or cell destruction. CGC staff also generate strains to enhance the collection of genetic tools available to the research community, engineering deletions of microRNA genes not yet represented in the collection and marking balancer chromosomes with fluorescent reporter genes to increase ease of use.

Services Provided

The CGC collection contains nearly 22,000 nematode strains available to order by investigators conducting research on this genetic model organism. Stocks are also provided to instructors for educational use. The CGC has stocks of nematode species closely related to C. elegans and bacterial strains necessary for nematode growth—for performing RNA interference experiments—and representative strains from the C. elegans microbiome collection. The CGC maintains a website with a searchable online catalog providing up-to-date information about strains available from the CGC. All strain requests must be submitted through the CGC web-based ordering system. New users must register their lab with the CGC and receive a lab code before ordering. Users can use links embedded in CGC pages to quickly and easily view relevant information about strains, genes, and genetics variations at WormBase. The CGC site also provides general information about C. elegans, with links to introductory methodology and websites of other key resources for researchers in the field, such as WormBook and WormAtlas. CGC staff are available by email or phone to answer questions about orders and strains.

Contact Information

Caenorhabditis Genetics Center
Department of Genetics and Cell Biology
University of Minnesota
6-160 Jackson Hall
321 Church St., SE
Minneapolis, MN 55455
Caenorhabditis Genetics Center (CGC)

Principal Investigator

Ann E. Rougvie, Ph.D.
rougvie@umn.edu

Head Curator

Aric Daul, Ph.D.
Phone: 612-625-2265
cgc@umn.edu