Impact of the Xenopus system on the missions of the NEI
Monica L. Vetter and Kathryn B. Moore (University of Utah)
Xenopus has been a classic model system for eye and vision research due to the ease of embryological analysis and manipulation. For example, fundamental insights into retino-tectal connectivity (Sperry), lens induction (Grainger) and retinal cell determination (Harris) have come from work in Xenopus. More recently, with the development of modern molecular methodology Xenopus has consolidated its role as a unique and vital model for investigating development, physiology and disease of the vertebrate visual system.
Eye Development and Regeneration:
Xenopus is ideal for the study of eye development since histogenesis in the Xenopus eye is rapid, with all retinal cell types specified between 1 and 3 days of development. In addition, the eye can be reproducibly targeted by microinjection of blastomeres at early cleavage stages or by in vivo lipofection or electroporation at optic vesicle stages. This allows selective manipulation of gene expression in the eye, with subsequent analysis of effects on optic vesicle patterning and retinal cell fate. This powerful approach has uncovered multiple genes and pathways governing retinal cell fate determination. Important advances range from understanding the importance of basic helix-loop-helix transcription factors in vertebrate retinal cell fate decisions (Kanekar et al., 1997) to the first demonstration that vertebrate homebox proteins act to effect a cellular clock that times the generation of retinal cells (Decembrini et al., 2006).� Important achievements in understanding the relevance of signaling pathways to retinal cell fate include the discovery of a novel role for Hedgehog signaling in the transition of stem cell to transient amplifying progenitors (Locker et al., 2006) and the elucidation of the multiple roles that Wnt signaling plays in both embryonic (Van Raay et al., 2005) and post-embryonic eye development (Denayer et al., 2008).
In addition, the development of rapid and efficient methods for generating transgenic animals (Kroll and Amaya, 1996) has led to identification and fine-mapping of multiple eye-specific promoters targeting various cell populations in the developing and mature Xenopus eye. For example, promoters for Rx, Pax6, Ath5, X-linked juvenile retinoschisis (RS1) gene and rod opsin have all been mapped in Xenopus. These are powerful tools for targeting transgenes to the developing eye and for investigating the mechanisms underlying eye-specific gene regulation.
In Xenopus, the eye continues to grow throughout the life of the animal, so there is a true retinal stem cell population present at the margins of the eye in the ciliary marginal zone that drives growth of the eye and can also replace lost or damaged retinal neurons � a feature that is not shared in higher vertebrates. In fact, the cocktail of retinal stem cell/progenitor genes that are sufficient to generate complete functional ectopic eyes from pluripotent ectoderm cells in Xenopus has been defined (Viczian et al., 2009). In addition, retinal tissue can be regenerated from animal cap embryonic stem cells (Lan et al, 2009), RPE (Vergara and Del Rio-Tsonis K, 2009) and the lens of the eye can be regenerated from neighboring tissues (reviewed in Beck et al., 2009). Thus, Xenopus represents an important model system for understanding retinal stem biology as well as regeneration of ocular tissues.
Retinal Cell Biology & Physiology:
Transgenic methods in Xenopus have proved to be a powerful tool for investigating the cell biology of photoreceptors in vivo, in particular for studying protein targeting to photoreceptor outer segments. For example, it was recently shown in Xenopus that ankyrin-G binding is necessary and sufficient for targeting of the �1 subunit of the cyclic nucleotide-gated channel to rod outer segments (Kizhatil et al., 2009). Another study showed that the outer segment serves as a default destination for the trafficking of membrane proteins in photoreceptors (Baker et al., 2008). The high cone/rod ratio of Xenopus, combined with its powerful transgenic methods has proved to be a useful system for investigating rod-cone interactions both in development and disease states (Hamm et al., 2009).
All levels of the Xenopus visual system are amenable to fruitful study, including formation of appropriate connections at central targets. Tremendous advances have also been made in our understanding of retinal axon guidance in Xenopus. Recent studies have revealed how local protein synthesis contributes to directional steering of retinal growth cones as they navigate to their target (Leung et al., 2006). In addition, it was recently found that maturation of retinotectal synapses in the developing Xenopus laevis optic tectum is regulated by activation of ephrin-B reverse signaling (Lim et al., 2008). Another study investigated the early development and plasticity of local excitatory circuits in the optic tectum of Xenopus laevis tadpole, revealing important insights into how the response properties of the tectal network are modulated and optimized (Pratt et al., 2008). Thus connectivity and circuit formation in the visual system have been amenable to fruitful analysis in Xenopus.
Circadian oscillator mechanisms have been extensively studied in Xenopus laevis. The retina contains the essential components of the clock, and can be selectively manipulated using retinal cell-type-specific promoters to allow molecular dissociation of the circadian clock (Hayasaka et al, 2005).
Modeling Human Disease in Xenopus:
Xenopus is also suitable for modeling certain human ocular disease. For example mutations causing autosomal dominant retinitis pigmentosa (RP) in humans induce rod photoreceptor degeneration in Xenopus laevis (Tam and Moritz, 2006). This has led to additional important insights, such as a molecular mechanism for light sensitivity in RP (Tam and Moritz, 2007). These approaches will ultimately open up new avenues for rapidly testing the effects of certain human mutations on gene function in vivo.
Selected references:
Baker SA, Haeri M, Yoo P, Gospe SM 3rd, Skiba NP, Knox BE, Arshavsky VY. (2008) The outer segment serves as a default destination for the trafficking of membrane proteins in photoreceptors. J Cell Biol., 183:485-498.
Beck CW, Izpis�a Belmonte JC, Christen B. (2009) Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms. Dev Dyn. 238:1226-1248.
Denayer T, Locker M, Borday C, Deroo T, Janssens S, Hecht A, van Roy F, Perron M, Vleminckx K (2008) Canonical Wnt signaling controls proliferation of retinal stem/progenitor cells in postembryonic Xenopus eyes. Stem Cells 26: 2063-74.
Decimbrini S, Andreazzoli M, Vignali R, Barsacchi G, Cremisi F (2006) Timing the generation of distinct retinal cells by homeobox proteins. PLoS Biol 4:272.
Hamm LM,Tam BM, Moritz OL (2009) Controlled rod cell ablation in transgenic Xenopus laevis. Invest Ophthalmol Vis Sci 50(2): 885-92.
Hayaaka N, LaRue SI, Green CB. (2005) Genetic manipulation of circadian rhythms in Xenopus. Methods Enzymol. 393:205-219.
Kizhatil K, Baker SA, Arshavsky VY, Bennett V. (2009) Ankyrin-G promotes cyclic nucleotide-gated channel transport to rod photoreceptor sensory cilia. Science 323:1614-1617.
Lan LA, Vitobello A, Bertacchi M, Cremisi F, Vignali R, Andreazzoli M, Demontis GC, Barsacchi G, Casarosa S (2009) Noggin Elicits Retinal Fate In Xenopus Animal Cap Embryonic Stem Cells. Stem Cells 27:2146-2152.
Leung KM, van Horck FP, Lin AC, Allison R, Standart N, Holt CE. (2006) Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1. Nat Neurosci. 9:1247-1256.
Lim BK, Matsuda N, Poo MM (2008) Ephrin-B reverse signaling promotes structural and functional synaptic maturation in vivo. Nat Neurosci., 11:160-169.
Locker MM,� Agathocleous M, Amato MA, Parain K, Harris WA, Perron, M et al. (2006) Hedgehog signaling and the retina: insights into the mechanisms controlling the proliferative properties of neural precursors �Genes Dev 20(21): 3036-48.
Pratt KG, Dong W, Aizenman CD. (2008) Development and spike timing-dependent plasticity of recurrent excitation in the Xenopus optic tectum. Nat Neurosci., 11:467-475.
Tam BM, Moritz OL. (2006) Characterization of rhodopsin P23H-induced retinal degeneration in a Xenopus laevis model of retinitis pigmentosa.� Invest Ophthalmol Vis Sci. 47:3234-3241.
Tam BM, Moritz OL. (2007) Dark rearing rescues P23H rhodopsin-induced retinal degeneration in a transgenic Xenopus laevis model of retinitis pigmentosa: a chromophore-dependent mechanism characterized by production of N-terminally truncated mutant rhodopsin. J Neurosci. 27:9043-9053.
Van Raay TJ, Moore KB, Iordanova I, Steele M, Jamrich M, Harris WA, Vetter ML (2005) Frizzled 5 signaling governs the neural potential of progenitors in the developing Xenopus retina. Neuron 46(1): 23-36.
Vergara MN, Del Rio-Tsonis K. (2009) Retinal regeneration in the Xenopus laevis tadpole: a new model system. Mol Vis. 15:1000-1013.
Viczian AS, Solessio EC, Lyou Y, Zuber ME (2009) Generation of functional eyes from pluripotent cells. PLoS Biol. 7:e1000174.
Xenopus Grants funding by the NEI
According to NIH RePORTER Search Tool, in the fiscal year of 2009, the National Energy Institute (NEI) funded 41 grants for projects involving Xenopus. These grants total $13,565,485.� See appendix for a complete list.
2009 Xenopus White Paper � Community Needs
Executive Summary
Xenopus - a crucial model organism for biomedical research:
Experiments in model animals are a cornerstone of biomedical research and have a massive impact on our understanding of human health and disease.� The frog, Xenopus, is a widely used and crucial vertebrate model organism that offers a unique combination of three powerful advantages:� strong conservation of essential biological mechanisms, a remarkable experimental repertoire, and unparalleled cost-effectiveness when compared to murine or other mammalian models.�
In fact, for many experimental applications, Xenopus is the only viable model system.� For example, in cell and molecular biology, Xenopus extracts allow for individual components of the cell cycle or DNA replication/repair machinery to be analyzed in a manner that cannot be recapitulated in vivo or in cell culture.� For developmental biology, no other model system allows for high-throughput genomic/proteomic screening and at the same time allows for transplant/explant analysis (i.e. �experimental embryology�).� The Xenopus oocyte is unique as a system for studying channel physiology using the patch-clamp and as a system for protein expression.� Finally, Xenopus is the only vertebrate model that readily produces enough biological material for biochemical purification from eggs, intact embryos, or isolated embryonic tissues.� The combination of these characteristics offers a wide range of experimental opportunities for studies using the Xenopus system in contrast to other vertebrates such as the mouse or zebrafish.
NIH Investment in Xenopus:
����������� The NIH has made a substantial and continuing investment in Xenopus research.� Indeed, a search of the NIH rePORT database for R01�s or equivalent grants using the search term �Xenopus� returned 427 grants for a total cost of $127,583,776 for FY08 and FY09.� Despite this investment in individuals� research, the Xenopus community lacks many resources that are considered entirely essential for other model systems, including a complete genome sequence, stock and training centers, and a comprehensive model organism database.
Xenopus as a Model System and Human Disease:
Given the tremendous advantages of the Xenopus system, the pace of new biological discovery by the Xenopus Community is brisk.� Using Xenopus, we have significantly improved our understanding of human disease genes and their mechanisms, justifying the NIH�s investment in Xenopus.� Below we provide examples of just a few of the human health discoveries made in the last two years:
Xenopus embryos are used for in vivo analysis of gene expression and function:
Nephronophthisis - Hum Mol Genet. 2008. 17, 3655-62; Nat Genet. 2005. 37, 537-43.
Cutis laxa - Nat Genet. 2009. 41, 1016-21.
Meckel-Gruber syndrome - Am J Hum Genet. 2008. 82, 959-70.
Colorectal cancer - Genome Res. 2009.� 19, 987-93.
Xenopus egg extracts are used for in vitro biochemical studies:
Fanconi Anemia - Mol. Cell. 2009. 35, 704-15;� J Biol Chem. 2009, 284, 25560-8.
C-myc oncogene - Nature. 2007. 448, 445-51.
BRCA1 - Cell. 2006. 127, 539-552
Xenopus oocytes are used to study gene expression and channel activity:
Trypanosome transmission - Nature 2009. 459, 213-217.
Epilepsy, ataxia, sensorineural deafness - N Engl J Med. 360, 1960-70.
Catastrophic cardiac arrhythmia (Long-QT syndrome) - PNAS �2009. 106,13082-7.
Megalencephalic leukoencephalopathy - Hum Mol Genet. 2008. 17, 3728-39.
Xenopus as a Model System and Basic Biological Processes:
Xenopus also plays a crucial role in elucidating the basic cellular and biochemical mechanisms underlying the entire spectrum of human pathologies.� Again only a few of the many discoveries in the last two years are highlighted here:
Xenopus embryos were used for studies of TGF-� signal transduction.
(Cell. 2009. 136,123-35; Science. 2007. 315, 840-3).
Xenopus egg extracts revealed fundamental aspects of cell division.
(Nature. 2008. 453, 1132-6; Science. 2008. 319, 469-72).
Xenopus embryos were used for studying mucociliary epithelia.
(Nat Genet. 2008. 40, 871-9; Nature. 2007. 447, 97-101).
Xenopus embryos were used for studying development of the vasculature.
(Cell. 2008.135, 1053-64).
Xenopus egg extracts provided key insight into DNA damage responses. �
(Mol Cell.� 2009. 35,704-15; Cell. 2008. 134, 969-80).
Xenopus embryos linked telomerase to Wnt signaling.
(Nature. 2009. 460, 66-72).
Xenopus was used for small molecule screens to develop therapeutics.
(Nat Chem Biol. 2008. 4, 119-25; Blood. 2009. 114, 1110-22).
Immediate Needs of the Xenopus Community:
����������� It is the consensus of the Xenopus community that their biomedical research could be greatly accelerated by the development of key resources that are currently lacking.� These resources would be of use to the entire Xenopus research community.� In this White Paper, the community identifies seven resources in two categories: Three Immediate Needs and four Essential Resources:
The Immediate Needs are a common set of key resources that were identified as the most pressing by three committees established to identify needed resources across the broad and diverse Xenopus community.� There is a broad, community-wide consensus that these resources would have an immediate impact on all Xenopus users and should be assigned the highest priority in order to accelerate the pace of biomedical research using Xenopus as a model system.�
����������� These Immediate Needs and the resulting improvements in biomedical research are as follows:
1.� Establishment of the Xenopus Resource and Training Center at the MBL in Woods Hole.
-Will allow rapid distribution of transgenic Xenopus laevis lines expressing fluorescent reporters and tagged proteins (for example histone-RFP for visualizing the mitotic spindle or organ specific GFP in embryos)
-Will allow centralized generation, housing, and distribution of genetically modified X. tropicalis lines, including both mutants and transgenics.
-Will allow both current investigators and the next generation of researchers to get hands-on training in� Xenopus-based biomedical research methods (including cell, molecular, and developmental methods).
2.� Expansion and improvement of Xenbase, a Xenopus model organism database.
-Maintain and curate data for the essential primary database for Xenopus researchers.
-Enhance the functionality of Xenbase by introducing a phenotypes feature.
-Support new content on Xenbase, including proteomics support, a new genome browser, and Wiki for Xenopus methods.
-Continue and expand collaborative and service efforts (e.g. provide Xenopus data to other databases including NCBI, UniProtK, Mascot and Tornado).
3.� Complete sequencing of the Xenopus laevis genome.
-Will allow the deconvolution of data in mass-spectrometry-based proteomic studies.
-Will facilitate identification of conserved gene regulatory regions to build gene-regulatory networks.
-Will facilitate site-specifc studies of DNA transaction (repair and replication)
-Will facilitate identification of all ORFs to build an ORFeome for rapid functional characterization of genes
-Will facilitate the design of morpholino oligonucleotides for gene depletion studies
-Will faciliate the analysis of chromatin-immunoprecipitations to identify DNA-bound to transcription factors and DNA modifications.
Essential Resources Needed by the Xenopus Community:
����������� In addition to these immediate, community-wide needs, the committees identified four Essential Resources that should be developed as soon as possible, so that Xenopus biologists can more effectively fulfill the missions of the NIH.� The Xenopus community considers all four of these additional resources to be essential, but understands that priorities must be set, and ranks these behind the Immediate Needs. These Essential Resources are as follows:
4.� Xenopus ORFeome in recombineering vectors.��
5.� Improvement of the X. tropicalis genome sequence and annotation
6.� Development of methods for disrupting gene function in Xenopus.
7. �Generation and Distribution of antibodies for Xenopus research.
Anticipated Gains for Biomedical Research:
����������� Xenopus is a crucial model organism for biomedical research.� With the development of large-scale community-wide resources, Xenopus is poised to be become the premier vertebrate model for systems-level approaches to understanding biological mechanisms in cell, molecular, and developmental biology.
The National Research Council and the National Academy of Sciences have recently called on the Unites States �to launch a new multiagency, multiyear, and multidisciplinary initiative to capitalize on the extraordinary advances recently made in biology�.� This report (http://www.nap.edu/catalog.php?record_id=12764) recommends the term "new biology" to describe an approach to research where �physicists, chemists, computer scientists, engineers, mathematicians, and other scientists are integrated into the field of biology.�� The promise of systems-level analysis in Xenopus, combined with its already proven strengths, make Xenopus the ideal model organism for pursuing this �new biology.�
Genome improvements will provide Xenopus researchers with the ability to perform genome-wide screens for biological activities that will in turn allow the rapid assembly and analysis of gene regulatory networks.� The ORFeome will greatly facilitate such genome-wide screening by allowing all ORFs to be rapidly analyzed or large numbers of proteins to be tagged for analysis of protein-protein interaction or for in vivo visualization.� Using extracts and biochemical purification coupled with mass-spectrometry and genomic sequence, protein interactomes can be rapidly identified and validated.� Because Xenopus can be so easily manipulated and because vast amounts of biological material can be generated, cell-type specific interactomes can also be identified.� Large-scale genetic screens will identify important novel genes in developmental pathways, especially given the relatively simple genome of X. tropicalis compared to zebrafish.� Finally, the flexibility of both Xenopus extracts and embryos make this system ideal for chemical biology screens.� Identifying these gene-regulatory networks, interactomes, and novel genes will be only the first steps, of course.� The well-established power of Xenopus for rapid analysis of gene function will then allow deeply mechanistic analyses to complement the systems-level approaches described above.�
It is the combination of these characteristics that distinguishes Xenopus from other vertebrate model systems such as mouse and zebrafish and allows for a systems-level approach to understanding biological mechanisms.� The tremendous promise of the Xenopus model cannot be realized, however, without the immediate development of community-wide research resources.� This White Paper presents the needed resources, and we look to the NIH for guidance in how to best achieve these goals.
For complete details of the 2009 Xenopus White Paper, please visit
Appendix
Xenopus Grants funded by the NEI
|
Project Number |
Activity |
Project Title |
Principal Investigator |
Organization |
Total |
|
|
5R01EY010843-16 |
R01 |
REGULATION OF RETINAL CGMP PHOSPHODIESTERASES |
ARTEMYEV, NIKOLAI O |
UNIVERSITY OF IOWA |
$370,972 |
|
|
3R01EY010843-16S1 |
R01 |
REGULATION OF RETINAL CGMP PHOSPHODIESTERASES |
ARTEMYEV, NIKOLAI O |
UNIVERSITY OF IOWA |
$54,082 |
|
|
2R01EY012682-10 |
R01 |
MOLECULAR MECHANISM OF PHOTORECEPTOR G PROTEIN SIGNALING |
ARTEMYEV, NIKOLAI O |
UNIVERSITY OF IOWA |
$367,000 |
|
|
7R01EY011261-14 |
R01 |
ACTIVITY DEPENDENT CONTROL OF VISUAL SYSTEM DEVELOPMENT |
CLINE, HOLLIS T |
SCRIPPS RESEARCH INSTITUTE |
$509,927 |
|
|
3R01EY011261-14S1 |
R01 |
ACTIVITY DEPENDENT CONTROL OF VISUAL SYSTEM DEVELOPMENT |
CLINE, HOLLIS T |
SCRIPPS RESEARCH INSTITUTE |
$185,209 |
|
|
5R01EY011912-12 |
R01 |
TROPHIC INTERACTIONS DURING VISUAL SYSTEM DEVELOPMENT |
COHEN-CORY, SUSANA |
UNIVERSITY OF CALIFORNIA IRVINE |
$375,105 |
|
|
2R01EY015788-06 |
R01 |
MECHANISMS OF VISUAL MAP DEVELOPMENT IN THE SUPERIOR COLLICULUS |
CRAIR, MICHAEL |
YALE UNIVERSITY |
$413,750 |
|
|
3R01EY015788-06S1 |
R01 |
MECHANISMS OF VISUAL MAP DEVELOPMENT IN THE SUPERIOR COLLICULUS |
CRAIR, MICHAEL |
YALE UNIVERSITY |
$299,240 |
|
|
5F32EY018066-04 |
F32 |
PRESYNAPTIC REGULATION OF DENDRITIC STRUCTURAL DYNAMICS |
DEMAS, JAMES ANTHONY |
SCRIPPS RESEARCH INSTITUTE |
$53,354 |
|
|
5R01EY013246-08 |
R01 |
MOLECULAR SCAFFOLDING FOR PHOTORECEPTOR OUTER SEGMENT STRUCTURE AND RENEWAL. |
GOLDBERG, ANDREW FX |
OAKLAND UNIVERSITY |
$360,138 |
|
|
3R01EY013246-07S1 |
R01 |
MOLECULAR SCAFFOLDING FOR PHOTORECEPTOR OUTER SEGMENT STRUCTURE AND RENEWAL. |
GOLDBERG, ANDREW FX |
OAKLAND UNIVERSITY |
$21,161 |
|
|
5R01EY013849-07 |
R01 |
CATARACTOGENESIS, CONNEXIN MUTANTS AND GENETIC MODIFIERS |
GONG, XIAOHUA |
UNIVERSITY OF CALIFORNIA BERKELEY |
$380,000 |
|
|
3R01EY013849-07S1 |
R01 |
CATARACTOGENESIS, CONNEXIN MUTANTS AND GENETIC MODIFIERS |
GONG, XIAOHUA |
UNIVERSITY OF CALIFORNIA BERKELEY |
$310,000 |
|
|
5R01EY009412-15 |
R01 |
INTERPHOTORECEPTOR RETINOID BINDING PROTEIN: STRUCTURE AND FUNCTION |
GHOSH, DEBASHIS ;GONZALEZ-FERNANDEZ, FEDERICO ; |
STATE UNIVERSITY OF NEW YORK AT BUFFALO |
$394,396 |
|
|
5R01EY017400-04 |
R01 |
GENETIC CONTROL OF EARLY RETINAL DEVELOPMENT |
GRAINGER, ROBERT M |
UNIVERSITY OF VIRGINIA CHARLOTTESVILLE |
$366,433 |
|
|
1R01EY018000-01A2 |
R01 |
GENOMIC SURVEY OF CIS-REGULATORY ELEMENT FUNCTION BY HIGH-THROUGHPUT TRANSGENESIS |
GRAINGER, ROBERT M |
UNIVERSITY OF VIRGINIA CHARLOTTESVILLE |
$355,746 |
|
|
2R01EY005661-24 |
R01 |
STRUCTURE AND FUNCTION OF LENS CHANNELS |
HALL, JAMES EWBANK |
UNIVERSITY OF CALIFORNIA IRVINE |
$482,795 |
|
|
5R01EY009844-14 |
R01 |
MOLECULAR AND CELLULAR BASIS OF LENS DEVELOPMENT |
HENRY, JONATHAN J |
UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN |
$283,483 |
|
|
5R01EY012085-12 |
R01 |
INTERCELLULAR COMMUNIATION IN THE EYE LENS |
JIANG, JEAN X |
UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT |
$365,000 |
|
|
3R01EY012085-11S1 |
R01 |
INTERCELLULAR COMMUNIATION IN THE EYE LENS |
JIANG, JEAN X |
UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT |
$302,637 |
|
|
5R01EY012975-08 |
R01 |
MOLECULAR MECHANISMS OF PHOTORECEPTOR FUNCTION |
KNOX, BARRY E |
UPSTATE MEDICAL UNIVERSITY |
$314,000 |
|
|
5R01EY018168-03 |
R01 |
NOVEL MECHANISM OF INDUCTION OF EYE TISSUE: KATP CHANNEL MODULATION |
LEVIN, MICHAEL |
TUFTS UNIVERSITY MEDFORD |
$338,153 |
|
|
5R01EY005477-25 |
R01 |
RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERS |
LIPTON, STUART A |
BURNHAM INSTITUTE FOR MEDICAL RESEARCH |
$463,653 |
|
|
1F31EY019843-01 |
F31 |
CHARACTERIZATION OF DIVERSE MELANOPSIN-EXPRESSING CELLS IN ZEBRAFISH |
MATOSCRUZ, VANESSA |
CARNEGIE INSTITUTION OF WASHINGTON, D.C. |
$30,955 |
|
|
5R01EY016807-03 |
R01 |
CIRCADIAN PHOTOENTRAINMENT IN MAMMALS |
PANDA, SATCHIDANANDA |
SALK INSTITUTE FOR BIOLOGICAL STUDIES |
$478,750 |
|
|
5R01EY006891-19 |
R01 |
MEMBRANE BIOSYNTHESIS IN NORMAL AND DYSTROPHIC RETINA |
PAPERMASTER, DAVID S |
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT |
$462,014 |
|
|
5R00EY018085-04 |
R00 |
TOWARDS A STRUCTURAL AND TEMPORAL UNDERSTANDING OF PHOTOTRANSDUCTION |
PARK, PAUL S |
CASE WESTERN RESERVE UNIVERSITY |
$249,000 |
|
|
3R00EY018085-04S1 |
R00 |
TOWARDS A STRUCTURAL AND TEMPORAL UNDERSTANDING OF PHOTOTRANSDUCTION |
PARK, PAUL S |
CASE WESTERN RESERVE UNIVERSITY |
$80,484 |
|
|
5R01EY016094-04 |
R01 |
DEVELOPMENT OF NANOSCALE NEUROMODULATING PLATFORMS |
PEPPERBERG, DAVID R |
UNIVERSITY OF ILLINOIS AT CHICAGO |
$1,248,803 |
|
|
3R01EY016094-04S1 |
R01 |
DEVELOPMENT OF NANOSCALE NEUROMODULATING PLATFORMS |
PEPPERBERG, DAVID R |
UNIVERSITY OF ILLINOIS AT CHICAGO |
$530,341 |
|
|
5R01EY017809-10 |
R01 |
RETINAL NEURONS AFFERENT TO THE CIRCADIAN SYSTEM |
PICKARD, GARY EDWARD |
UNIVERSITY OF NEBRASKA LINCOLN |
$372,652 |
|
|
2R01EY014979-05A2 |
R01 |
DEVELOPMENT AND PLASTICITY OF A RETINOTECTAL SYSTEM |
POO, MU-MING |
UNIVERSITY OF CALIFORNIA BERKELEY |
$333,031 |
|
|
5F32EY018981-02 |
F32 |
CNG CHANNEL GATING MOVEMENTS MONITORED VIA FLUORESCENE QUENCHING |
PULJUNG, MICHAEL C |
UNIVERSITY OF WASHINGTON |
$53,354 |
|
|
2R01EY011105-14 |
R01 |
CHEMICAL ARCHITECTURE OF RETINAL CIRCUITS |
VARDI, NOGA |
UNIVERSITY OF PENNSYLVANIA |
$590,453 |
|
|
1R21EY019758-01 |
R21 |
THE ROLE OF PHOSPHORYLATION IN PHOTORECEPTOR CELL BIOLOGY |
WEISS, ELLEN RUTH |
UNIVERSITY OF NORTH CAROLINA CHAPEL HILL |
$185,000 |
|
|
5R01EY011900-12 |
R01 |
RGS PROTEIN FUNCTION IN MAMMALIAN RETINA |
WENSEL, THEODORE G |
BAYLOR COLLEGE OF MEDICINE |
$364,125 |
|
|
5T32EY007001-34 |
T32 |
RESEARCH TRAINING IN VISUAL SCIENCES |
WU, SAMUEL M. |
BAYLOR COLLEGE OF MEDICINE |
$193,315 |
|
|
5R01EY006837-22 |
R01 |
PHOTOTRANSDUCTION AND SIGNALING IN PHOTORECEPTORS |
YAU, KING-WAI |
JOHNS HOPKINS UNIVERSITY |
$410,000 |
|
|
5R01EY018141-03 |
R01 |
ENZYMATIC AND MOTOR PROPERTIES OF MYOSIN III |
YENGO, CHRISTOPHER M |
PENNSYLVANIA STATE UNIV HERSHEY MED CTR |
$257,926 |
|
|
3R21EY018111-02S1 |
R21 |
DEVELOPMENT OF A MODEL SYSTEM FOR PRESYNAPTIC STUDY |
ZENISEK, DAVID PAUL |
YALE UNIVERSITY |
$84,298 |
|
|
5R01EY017964-03 |
R01 |
GENETIC REGULATORY NETWORK CONTROLLING VERTEBRATE EYE FORMATION |
ZUBER, MICHAEL E |
UPSTATE MEDICAL UNIVERSITY |
$274,750 |
|
|
|
|
|
|
Total: |
$13,565,485 |
|