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Impact of the Xenopus system on the missions of the NIGMS

John Wallingford, PhD - HHMI & University of Texas at Austin

Eddy DeRobertis, MD, PhD - HHMI & University of California Los Angeles

Jean Gautier, PhD � Columbia University

Yixian Zheng, PhD � HHMI & Carnegie Institution

 

The NIGMS �supports basic research that increases understanding of life processes and lays the foundation for advances in disease diagnosis, treatment, and prevention� (http://www.nigms.nih.gov/Initiatives/).� Experiments in model animals are a cornerstone of such fundamental biomedical research and they play a particularly important role in the mission of the NIGMS.��

The frog, Xenopus, is a widely used and crucial vertebrate model organism that is unique for its combination of its experimental tractability and its close evolutionary relationship with humans.� Xenopus is an essential tool for in vivo studies in molecular, cell, and developmental biology of vertebrate animals.� However, the enormous breadth of Xenopus research stems from the additional fact that cell-free extracts made from Xenopus are a premier in vitro system for studies of fundamental aspects of cell and molecular biology.� Thus, Xenopus is the only vertebrate model system that allows for high-throughput in vivo analyses of gene function and high-throughput biochemistry.� Finally, it should be borne in mind that Xenopus oocytes are a leading system for studies of ion transport and channel physiology.�

Because of its diverse applications, Xenopus research is funded by nearly all Institutes within the NIH.� However, the NIGMS remains by far the largest source of funding for Xenopus research.� In this statement, we provide a summary of the crucial contributions made by Xenopus research to the mission of the NIGMS.�� We start with recent contributions of Xenopus to the study of known human disease genes.� We follow this with a selection of examples that illustrate the huge impact that recent Xenopus research has had on our understanding of fundamental biological processes.� Finally, we summarize very briefly the long and rich history which formed the foundation for myriad current advances being made Xenopus research to our understanding of the biology underlying human disease.

 

I.� Direct investigation of human disease genes using Xenopus:

 

The NIGMS funds research that �lays the foundation for advances in disease diagnosis, treatment, and prevention� (http://www.nigms.nih.gov/Initiatives/).� Therefore, it is notably that all modes of Xenopus research (embryos, cell-free, extracts, and oocytes) are now commonly and widely used in direct study of human disease genes.�

 

Xenopus embryos for in vivo studies of human disease gene function:�� Xenopus embryos are large and easily manipulated, and moreover, many hundreds of embryos can be obtained in a single day.� It is not surprising, then, that Xenopus was the first vertebrate animal for which methods were developed that allowed rapid analysis of gene function using misexpression (by mRNA injection; Nature. 1971. 233, 177-82).� Indeed, injection of mRNA in Xenopus led to the cloning of interferon (PNAS. 1975. 72, 4881-4885).� Moreover, the use of morpholino-antisense oligonucleotides for gene knockdowns in vertebrates, which is now the state-of-the-art, was first developed by Janet Heasman using Xenopus (Dev. Biol. 2000. 222, 124-34.).�

In recent years these approaches have played in important role in studies of human disease genes.� The mechanism of action for several genes mutated in human cystic kidney disorders (e.g. nephronophthisis) have been extensively studied in Xenopus embryos, shedding new light on the link between these disorders, ciliogenesis and Wnt signaling (Hum Mol Genet. 2008. 17, 3655-62).� Xenopus embryos have also provided a rapid test bed for validating newly-discovered disease genes.� For example, studies in Xenopus confirmed and elucidated the role PYCR1 in cutis laxa with progeroid features (Nat Genet. 2009. 41, 1016-21).

 

Transgenic Xenopus for studying transcriptional regulation of human disease genes:Xenopus embryos develop rapidly, and so transgenesis in Xenopus is a rapid and effective method for analyzing genomic regulatory sequences.� In a recent study, mutations in the SMAD7 locus were revealed to associate with human colorectal cancer.� Interestingly, the mutations lay in conserved, but non-coding sequences, suggesting that these mutations impacted the patterns of SMAD7 transcription.� To test this hypothesis, the authors used Xenopus transgenics, and revealed that this genomic region drove expression of GFP in the hindgut.� Moreover, transgenics made with the mutant version of this region displayed substantially less expression in the hindgut (Genome Res. 2009. 19, 987-93.).

 

Xenopus cell-free extracts for biochemical studies of proteins encoded by human disease genes: A unique advantage of the Xenopus system is that cytosolic extracts contain both soluble cytoplasmic and nuclear proteins (including chromatin proteins). This is in contrast to cellular extracts prepared from somatic cells with already distinct cellular compartments.� Xenopus egg extracts have provided innumerable insights into the basic biology of cells with particular impact on cell division and the DNA transactions associated with it.

Studies in Xenopus egg extracts have also yielded critical insights into the mechanism of action of human disease genes associated with genetic instability and elevated cancer risk, such as ATM (Ataxia telangiectasia), BRCA1 (Inherited Breast and Ovarian cancer), Nbs1 (Nijmegen Breakage Syndrome), RecQL4 (Rothmund-Thomson Syndrome), c-Myc oncogene and FANC proteins (Fanconi anemia) (Cell. �2006, 127, 539-52; Nat. Cell Biol. 2007. 9, 1311-18; Mol. Cell.  2009. 35, 704-15; J Biol Chem. 2009, 284, 25560-8; Nature. 2007. 448, 445-51).

 

Xenopus oocytes for studies of gene expression and channel activity related to human disease:Yet another strength of Xenopus, and another strength that is simply not matched by any other vertebrate model system, is the ability to rapidly and easily assay the activity of channel and transporter proteins using expression in oocytes.� This application has also led to important insights into human disease, including studies related to trypanosome transmission (Nature 2009. 459, 213-217), Epilepsy with ataxia and sensorineural deafness (N Engl J Med. 360, 1960-70), Catastrophic cardiac arrhythmia (Long-QT syndrome; PNAS �2009. 106,13082-7) and Megalencephalic leukoencephalopathy (Hum Mol Genet. 2008. 17, 3728-39).

 

II.� Investigation of fundamental biological processes using Xenopus:

 

����������� In addition to applied studies directed at the mechanisms of known human disease genes, the NIGMS very broadly supports �basic research that increases understanding of life processes� (http://www.nigms.nih.gov/Initiatives/).� It is this area where Xenopus has made its most substantive and wide-ranging contributions.�

To name only a few areas of study in which Xenopus has had a large impact in the last two years:

 

Signal transduction:Xenopus embryos and cell-free extracts are widely used for basic research in signal transduction.� In just the last few years, Xenopus embryos have� provided crucial insights into the mechanisms of TGF- and Wnt signal transduction.� For example, Xenopus embryos were used to identify the enzymes that control ubiquitination of smad-4 (Cell. 2009. 136,123-35), and also to demonstrate direct links between TGF- superfamily signaling pathways and other important networks, such as the MAP kinase pathway (Science. 2007. 315, 840-3) and the Wnt pathway (Cell. 2007.� 131, 980-993).� Moreover, new methods using egg extracts revealed novel, important targets of the Wnt/GSK3 destruction complex (PNAS.� 2009. 106, 5165-5170).�

 

Cell division:� Xenopus egg extracts have allowed the study of many complicated cellular events in a test tube.� Because egg cytosol can support successive cycling between mitosis and interphase in vitro, it has been critical to diverse studies of cell division.� For example, the small GTPase Ran was first found to regulate interphase nuclear transport, but Xenopus egg extracts revealed the critical role of Ran GTPase in mitosis independent of its role in interphase nuclear transport (Nature. 2006 440, 697-701).� Similarly, the cell-free extracts were used to model nuclear envelope assembly from chromatin, revealing the function of RanGTPase in regulating nuclear envelope reassembly after mitosis (Science 2006 311, 1887-1893).� More recently, using Xenopus egg extracts, it was possible to demonstrate the mitosis-specific function of the nuclear lamin B in regulating spindle morphogenesis (Nat. Cell Biol. 2009. 11, 247-256) and to identify new proteins that mediate kinetochore attachment to microtubules (Cell. 2007. 130, 893-905.

Embryonic development:Xenopus embryos are so widely used in developmental biology that it is impossible to quickly summarize the myriad of important advances made by Xenopus research in recent years.� A very short list would include:

    Epigenetics of cell fate specification (Dev. Cell. �2009. 17, 425-434),

    microRNAs in germ layer patterning and eye development

(Dev. Cell. 2009. 16, 517-527; Genes & Dev. 2009.� 23, 1046-1051)

    Link between Wnt signaling and telomerase (Nature. 2009. 460, 66-72),

    Development of the vasculature (Cell. 2008.135, 1053-64),

    Gut morphogenesis (Genes & Dev. 2008. 22, 3050-3063),

    Contact inhibition and neural crest cell migration (Nature. 2008. 146, 957-961).

 

Initiation of DNA replication:� Xenopus cell-free extracts also support the synchronous assembly and the activation of origins of DNA replication. They have been instrumental in characterizing the biochemical function of the pre-replicative complex, including MCM proteins (Mol. Cell. 2008. 32, 862-9; EMBO J. 2009. 28, 3005-14).

 

�Response to DNA damage: Cell-free extracts have been instrumental to unravel the signaling pathways that are activated in response to DNA double-strand breaks (ATM), replication fork stalling (ATR) or DNA interstrand crosslinks (FA proteins and ATR). Notably, several mechanisms and components of these signal transduction pathways were first identified in Xenopus (Mol Cell.� 2009. 35,704-15; Cell. 2008. 134, 969-80; Genes Dev. 2007. 21, 898-903).

 

Apoptosis: Xenopus oocytes provide a tractable model for biochemical studies of apoptosis.� Recently, oocytes were used recently to study the biochemical mechanisms of caspase-2 activation;� importantly, this mechanism turns out to be conserved in mammals (Dev Cell. 2009. 16, 856-66).��

 

Regenerative medicine:� In recent years, there has been tremendous interest in developmental biology stoked by the promise of regenerative medicine.� Xenopus has played a role here as well.� For example, it has been found that expression of seven transcription factors in pluripotent Xenopus cells rendered those cells able to develop into functional eyes when implanted into Xenopus embryos, providing potential insights into the repair of retinal degeneration or damage (PLoS Biology. 2009.� 7, e1000174.).�

In a vastly different study, Xenopus embryos was used to study the effects of tissue tension on morphogenesis (Dev Cell. 2009.� 16, 421-432.), an issue that will be critical for in vitro tissue engineering.

�����������

Physiology:� The directional beating of multi-ciliated cells is essential to development and homeostasis in the central nervous system, the airway, and the oviduct.� Interestingly, the multi-ciliated cells of the Xenopus epidermis have recently been developed as the first in vivo test-bed for live-cell studies of such ciliated tissues, and these studies have provided important insights into the biomechanical and molecular control of directional beating (Nat Genet. 2008. 40, 871-9; Nature. 2007. 447, 97-101).

 

 

III.� Use of Xenopus for small molecule screens to develop novel therapeutics.��

Because huge amounts of material are easily obtained, all modalities of Xenopus research are now being used for small-molecule based screens.�

 

Chemical genetics of vascular growth in Xenopus tadpoles:� Given the important role of neovascularization in cancer progression, Xenopus embryos were recently used to identify new small molecules inhibitors of blood vessel growth.� Notably, compounds identified in Xenopus were effective in mice (Blood. 2009. 114, 1110-22; Blood.� 2008. 112, 1740-9).�

 

In vivo testing of potential endocrine disruptors in transgenic Xenopus embryos:� Endocrine disrupting chemical released into the environment are pose a potential public health risk, but our ability to identify such compounds in vitro vastly outstrips our ability to monitor the in vivo effects of such chemicals.� A high-throughput assay for thyroid disruption has recently been developed using transgenic Xenopus embryos (Environ. Sci. Technol. �2007.� 41, 5908-14).

 

Small molecule screens in Xenopus egg extracts:� Egg extracts provide ready analysis of molecular biological processes and can rapidly screened.� This approach was used to identify novel inhibitors of proteasome-mediated protein degradation and DNA repair enzymes (Nat Chem Biol. 2008. 4, 119-25; Int. J. Cancer.� 2009. 124, 783-92).

 

 

IV.� A long history of research laid the foundation for the myriad recent contributions of Xenopus to biomedical science.��

 

In addition to its current wide usage in diverse areas of biology, we feel that it is also worth summarizing the some of the landmark discoveries that come to mind when thinking about the contributions of Xenopus to the NIH.

 

1950�s

    The discovery that somatic nuclei are totipotential, from which present excitement about nuclear reprogramming and stem cells arises (Gurdon et al., 1958).

 

1960�s

    1969: The discovery that the nucleolar organizer encodes the ribosomal RNA genes (Brown and Gurdon, 1969).

    1968: Selective DNA amplification of rDNA in oogenesis (Brown and Dawid, 1968; Gall, 1968).

    Mitochondrial DNA exists and is inherited from the mother (Dawid, 1966).

 

1970�s

    The isolation of the first eukaryotic genes by equilibrium density centrifugation in the form of rRNA and 5S genes (Birnstiel et al., 1968; Brown et al., 1971).

    The first eukaryotic translation system by oocyte mRNA microinjection (Gurdon et al., 1971).

    The first transcription and translation system for cloned genes (Brown and Gurdon, 1977; De Robertis and Mertz, 1977).

    Discovery of MPF, a meiosis maturation promoting factor that provided the key to the elucidation of the cell cycle (Wasserman and Masui, 1976).

    First system for electrophysiological studies on cloned membrane channels and receptors (Kusano et al., 1977).

    Identification of nuclear targeting signal sequences in the mature sequence of nuclear proteins (De Robertis et al., 1978).

 

1980�s

    The isolation of the first eukaryotic transcription factor, TFIIIA (Engelke et al., 1980).

    First in vitro system for nuclear and chromosome assembly (Lohka and Masui, 1983).

    Discovery of the first Hox gene homologue in vertebrates (Carrasco et al., 1984).

    Mesoderm induction is mediated by members of the TGF-beta family of growth factors (Smith, 1987).

    Cell cycle progression is regulated through protein degradation of cyclins via ubiquitinylation (Murray et al., 1989).

 

1990�s

    Realization that Homeobox genes direct gastrulation morphogenetic movements (Niehrs et al., 1993).

    Molecular nature of Spemann�s organizer: cell-cell signals are regulated by secreted growth factors antagonists such as Noggin, Gremlin, Follistatin, Chordin, Cerberus, Frzb and Dickkopf (reviewed by Harland and Gerhart, 1997).

    Identification of the cell-cell signals that cause induction and patterning of the Central Nervous System (Zimmerman et al., 1996; Piccolo et al., 1996).

 

These and many other past discoveries would more than justify a re-dedication of the NIGMS�s efforts to the acceleration and promotion of biomedical research using Xenopus.� But as the document above makes clear, the current, sustained contributions made by this system are such that Xenopus should be considered one of the most promising post-genomic systems for research in Cell and Molecular Biology.


Xenopus Grants funding by the NIGMS

 

According to NIH RePORTER Search Tool, in the fiscal year of 2009, the National Institute of General Medical Sciences (NIGMS) funded 152 grants for projects involving Xenopus. These grants total $43,883,452. �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

Xenopus White Paper


 

Appendix

 

Xenopus Grants funded by the NIGMS

 

Project Number

Activity

Project Title

Principal Investigator

Organization

Total

5K99GM084292-02

K99

MICROTUBULE POLYMERIZATION AND DEPOLYMERIZATION MECHANISMS BY CONSERVED PROTEINS

AL-BASSAM, JAWDAT MH

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$72,306

5R01GM084491-02

R01

ANALYSIS OF TYRAMINERGIC SIGNALING IN CAENORHABDITIS ELEGANS

ALKEMA, MARK

UNIV OF MASSACHUSETTS MED SCH WORCESTER

$327,667

5F31GM073576-05

F31

THE ROLE OF STU1 IN MITOTIC SPINDLE STABILITY

AMARO, IRENE A

CORNELL UNIVERSITY ITHACA

$36,429

5R01GM080278-03

R01

REGULATION AND FUNCTION OF PIASY MEDIATED MITOTIC SUMOYLATION IN VERTEBRATES

AZUMA, YOSHIAKI

UNIVERSITY OF KANSAS LAWRENCE

$247,326

3R01GM080278-03S1

R01

REGULATION AND FUNCTION OF PIASY MEDIATED MITOTIC SUMOYLATION IN VERTEBRATES

AZUMA, YOSHIAKI

UNIVERSITY OF KANSAS LAWRENCE

$125,244

5R01GM046889-16

R01

STRUCTURE/FUNCTION OF GAP JUNCTIONS

BARGIELLO, THADDEUS ANDREW

ALBERT EINSTEIN COL OF MED YESHIVA UNIV

$480,696

2R01GM030376-30

R01

THE ELECTROPHYSIOLOGICAL STUDIES OF VOLTAGE GATED CHANNELS

BEZANILLA, FRANCISCO J

UNIVERSITY OF CHICAGO

$490,032

3R01GM030376-30S1

R01

THE ELECTROPHYSIOLOGICAL STUDIES OF VOLTAGE GATED CHANNELS

BEZANILLA, FRANCISCO J

UNIVERSITY OF CHICAGO

$341,835

2R01GM044592-18A1

R01

MECHANISM AND REGULATION OF RECEPTOR-G PROTEIN SIGNALING

BLUMER, KENDALL JAY

WASHINGTON UNIVERSITY

$568,136

1P30GM092374-01

P30

REGENERATIVE BIOLOGY CENTER AT THE MBL

BORISY, GARY G

MARINE BIOLOGICAL LABORATORY

$401,250

5R01GM066977-08

R01

TGFB SIGNALING IN VERTEBRATE MESODERM INDUCTION

BRIVANLOU, ALI H

ROCKEFELLER UNIVERSITY

$311,788

1R01GM083970-01A1

R01

KINASE ACTIVATION IN THE DNA DAMAGE CHECKPOINTS

BURGERS, PETER M

WASHINGTON UNIVERSITY

$258,400

3R37GM030997-27S1

R37

GENETIC ANALYSIS OF NEMATODE CELL DIFFERENTIATION

CHALFIE, MARTIN

COLUMBIA UNIV NEW YORK MORNINGSIDE

$187,436

1R01GM083029-01A2

R01

ERBB SIGNALING IN VERTEBRATE MORPHOGENESIS

CHANG, CHENBEI

UNIVERSITY OF ALABAMA AT BIRMINGHAM

$304,633

3R01GM075018-04S1

R01

REGULATION OF CALL ADHESION IN XENOPUS

CHO, KEN W.Y.

UNIVERSITY OF CALIFORNIA IRVINE

$94,198

5R01GM078502-03

R01

STRUCTURE/FUNCTION ANALYSIS OF THE NA/BICARBONATE COTRANSPORTERS

CHOI, INYEONG

EMORY UNIVERSITY

$267,750

3R01GM078502-03S1

R01

STRUCTURE/FUNCTION ANALYSIS OF THE NA/BICARBONATE COTRANSPORTERS

CHOI, INYEONG

EMORY UNIVERSITY

$247,488

5R01GM029513-29

R01

MICROTUBULE REGULATION

CLEVELAND, DON W.

LUDWIG INSTITUTE FOR CANCER RESEARCH

$611,119

3R01GM029513-29S1

R01

MICROTUBULE REGULATION

CLEVELAND, DON W.

LUDWIG INSTITUTE FOR CANCER RESEARCH

$162,658

5K08GM083216-02

K08

VOLATILE ANESTHETIC REGULATION OF TASK TANDEM PORE POTASSIUM CHANNELS

COTTEN, JOSEPH F

MASSACHUSETTS GENERAL HOSPITAL

$130,928

3K08GM083216-02S1

K08

VOLATILE ANESTHETIC REGULATION OF TASK TANDEM PORE POTASSIUM CHANNELS

COTTEN, JOSEPH F

MASSACHUSETTS GENERAL HOSPITAL

$108,000

5R01GM074771-03

R01

KINASES IN ION COTRANSPORTER FUNCTION

DELPIRE, ERIC J

VANDERBILT UNIVERSITY

$332,056

5R01GM052302-14

R01

BIOGENESIS OF VOLTAGE-GATED K+ CHANNELS

DEUTSCH, CAROL J

UNIVERSITY OF PENNSYLVANIA

$758,729

5R01GM016317-41

R01

RNASES AND RNA METABOLISM IN BACTERIA

DEUTSCHER, MURRAY P

UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

$476,558

5SC3GM081165-02

SC3

MOLECULAR MECHANISMS UNDERLYING XENOPUS SOMITOGENESIS

DOMINGO, CARMEN R.

SAN FRANCISCO STATE UNIVERSITY

$115,032

5R01GM085456-02

R01

DE-DIFFERENTIATING ADULT HUMAN FIBROBLASTS INTO STEM-LIKE CELLS USING CONDITIONS

DOMINKO, TANJA

WORCESTER POLYTECHNIC INSTITUTE

$293,402

3R01GM085456-02S2

R01

DE-DIFFERENTIATING ADULT HUMAN FIBROBLASTS INTO STEM-LIKE CELLS USING CONDITIONS

DOMINKO, TANJA

WORCESTER POLYTECHNIC INSTITUTE

$104,069

2R01GM070891-05

R01

ROLE OF ATR IN CELL CYCLE CHECKPOINTS

DUNPHY, WILLIAM G.

CALIFORNIA INSTITUTE OF TECHNOLOGY

$466,716

5R01GM080570-03

R01

STRUCTURAL MECHANISMS OF MCM10 IN DNA REPLICATION

EICHMAN, BRANDT F

VANDERBILT UNIVERSITY

$274,595

1SC1GM086344-01

SC1

MOLECULAR PHYSIOLOGY OF Y-AMINOBUTYRIC ACID TRANSPORTERS

ESKANDARI, SEPEHR

CALIFORNIA STATE POLY U POMONA

$319,500

3SC1GM086344-01S1

SC1

MOLECULAR PHYSIOLOGY OF Y-AMINOBUTYRIC ACID TRANSPORTERS

ESKANDARI, SEPEHR

CALIFORNIA STATE POLY U POMONA

$39,283

5R01GM046383-20

R01

REGULATORS OF CDC2/CDK1

FERRELL, JAMES E.

STANFORD UNIVERSITY

$324,848

5R01GM077544-04

R01

BISTABILITY AND BIOLOGICAL OSCILLATIONS

FERRELL, JAMES E.

STANFORD UNIVERSITY

$258,867

5R01GM075249-05

R01

ROLES OF CHROMOSOMAL FACTORS IN CHROMOSOME SEGREGATION

FUNABIKI, HIRONORI

ROCKEFELLER UNIVERSITY

$304,460

2R01GM033397-25

R01

THE ORGANIZATION OF ANIMAL CELL NUCLEI

GALL, JOSEPH G.

CARNEGIE INSTITUTION OF WASHINGTON, D.C.

$423,325

5R01GM067758-06

R01

MECHANISM OF RNA LOCALIZATION IN DROSOPHILA DEVELOPMENT

GAVIS, ELIZABETH R.

PRINCETON UNIVERSITY

$332,289

3R01GM067758-06S1

R01

MECHANISM OF RNA LOCALIZATION IN DROSOPHILA DEVELOPMENT

GAVIS, ELIZABETH R.

PRINCETON UNIVERSITY

$457,756

5R01GM052111-11

R01

REGULATION OF COORDINATION OF MOLECULAR MOTORS

GELFAND, VLADIMIR I

NORTHWESTERN UNIVERSITY

$469,742

3R01GM048430-16S1

R01

DROSOPHILA GENES AFFECTING CHROMOSOME SEGREGATION

GOLDBERG, MICHAEL L

CORNELL UNIVERSITY ITHACA

$129,044

5R01GM083071-02

R01

MECHANISMS OF C. ELEGANS GASTRULATION

GOLDSTEIN, ROBERT P

UNIVERSITY OF NORTH CAROLINA CHAPEL HILL

$276,520

5R37GM037432-24

R37

CATENIN AND CADHERIN SIGNALING IN DEVELOPMENT AND CANCER

GUMBINER, BARRY M.

UNIVERSITY OF VIRGINIA CHARLOTTESVILLE

$535,210

5R01GM052717-14

R01

BIOCHEMISTRY AND REGULATION OF CADHERIN ACTIVITY

GUMBINER, BARRY M.

UNIVERSITY OF VIRGINIA CHARLOTTESVILLE

$373,676

3R01GM052717-14S1

R01

BIOCHEMISTRY AND REGULATION OF CADHERIN ACTIVITY

GUMBINER, BARRY M.

UNIVERSITY OF VIRGINIA CHARLOTTESVILLE

$234,053

5R01GM078172-03

R01

NON-CANOICAL WNT SIGNALING AND CELL MOTILITY

HABAS, RAYMOND

UNIV OF MED/DENT NJ-R W JOHNSON MED SCH

$263,334

5R01GM077336-03

R01

MOLECULAR CHARACTERIZATION OF HEPATIC ORGANIC ANION TRANSPORTING POLYPEPTIDES

HAGENBUCH, BRUNO

UNIVERSITY OF KANSAS MEDICAL CENTER

$320,550

2R01GM042341-23

R01

GENE EXPRESSION IN AMPHIBIAN DEVELOPMENT

HARLAND, RICHARD M.

UNIVERSITY OF CALIFORNIA BERKELEY

$363,392

1R01GM086321-01

R01

A HIGH QUALITY GENOME ASSEMBLY FOR XENOPUS TROPICALIS

HARLAND, RICHARD M. ;ROKHSAR, DANIEL ;

UNIVERSITY OF CALIFORNIA BERKELEY

$392,693

2R01GM070565-05

R01

SYSTEMATIC ANALYSIS OF PROTEOLYSIS PATHWAYS FOR CULLIN TARGETS

HARPER, JEFFREY WADE

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$321,869

3R01GM070565-05S1

R01

SYSTEMATIC ANALYSIS OF PROTEOLYSIS PATHWAYS FOR CULLIN TARGETS

HARPER, JEFFREY WADE

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$100,000

5F32GM082014-03

F32

MECHANISM OF PCNA-DEPENDENT CDT1 DESTRUCTION IN S PHASE

HAVENS, COURTNEY G

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$51,710

2R01GM057603-10A1

R01

STUDIES OF WNT RECEPTOR INTERACTION WITH AGONISTS AND ANTAGONISTS

HE, XI

CHILDREN'S HOSPITAL BOSTON

$425,184

5R01GM073994-04

R01

NUCLEAR MEMBRANE FUSION IN XENOPUS EGG EXTRACTS

HETZER, MARTIN W

SALK INSTITUTE FOR BIOLOGICAL STUDIES

$353,298

5R01GM072754-06

R01

MECHANISMS OF CENTROSOME REPRODUCTION IN ANIMAL CELLS

HINCHCLIFFE, EDWARD H

UNIVERSITY OF MINNESOTA TWIN CITIES

$254,722

5R01GM080993-03

R01

A CLONABLE HIGH-DENSITY FOR 3-D ELECTRON MICROSCOPY OF CELLULAR STRUCTURES

HOENGER, ANDREAS

UNIVERSITY OF COLORADO AT BOULDER

$265,125

5R01GM079427-18

R01

MOLECULAR PHYSIOLOGY OF VOLTAGE-GATED ION CHANNELS

HORN, RICHARD J

THOMAS JEFFERSON UNIVERSITY

$368,737

5R01GM083999-02

R01

LOCALIZED MRNAS IN VERTEBRATE AXIS FORMATION

HOUSTON, DOUGLAS W

UNIVERSITY OF IOWA

$281,316

1R01GM088202-01

R01

PLANAR CELL POLARITY AND THE CYTOSKELETON

JENNY, ANDREAS

ALBERT EINSTEIN COL OF MED YESHIVA UNIV

$327,776

5R01GM050806-16

R01

REGULATION OF DNA REPLICATION IN S. POMBE

KELLY, THOMAS J

SLOAN-KETTERING INSTITUTE FOR CANCER RES

$441,477

5R01GM064768-07

R01

FOX GENE REGULATION OF NODAL SIGNALING IN MESODERM DEVELOPMENT

KESSLER, DANIEL S

UNIVERSITY OF PENNSYLVANIA

$321,765

5R01GM033932-23

R01

ESTABLISHING GERM CELL FATE IN XENOPUS

KING, MARY LOU

UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

$349,123

5R01GM066492-07

R01

CHEMICAL GENETIC AND BIOCHEMICAL STUDIES OF MITOTIC PROTEOLYSIS

KING, RANDALL W

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$364,246

3R01GM066492-07S1

R01

CHEMICAL GENETIC AND BIOCHEMICAL STUDIES OF MITOTIC PROTEOLYSIS

KING, RANDALL W

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$199,678

2R01GM076507-05

R01

DEVELOPMENTAL PHYSIOLOGY OF CILIATED EPITHELIA

KINTNER, CHRISTOPHER ROBERT

SALK INSTITUTE FOR BIOLOGICAL STUDIES

$416,680

5R01GM076621-04

R01

EARLY ACTIVATION OF THE ZYGOTIC GENOME

KLEIN, PETER S

UNIVERSITY OF PENNSYLVANIA

$290,572

1R01GM084133-01A1

R01

NFKB TARGETS AND NEURAL CREST DEVELOPMENT

KLYMKOWSKY, MICHAEL W

UNIVERSITY OF COLORADO AT BOULDER

$317,292

5R01GM080333-03

R01

CONTROL OF CASPASE ACTIVATION IN APOPTOSIS

KORNBLUTH, SALLY A

DUKE UNIVERSITY

$288,600

3R01GM080333-03S1

R01

CONTROL OF CASPASE ACTIVATION IN APOPTOSIS

KORNBLUTH, SALLY A

DUKE UNIVERSITY

$225,036

1R01GM088175-01

R01

REGULATION OF M PHASE EXIT

KORNBLUTH, SALLY A

DUKE UNIVERSITY

$304,130

5R01GM066815-07

R01

TRANSCRIPTIONAL REGULATION BY GEMININ

KROLL, KRISTEN L

WASHINGTON UNIVERSITY

$288,800

3R01GM066815-07S1

R01

TRANSCRIPTIONAL REGULATION BY GEMININ

KROLL, KRISTEN L

WASHINGTON UNIVERSITY

$283,295

2R01GM037949-23

R01

GROUP II INTRON MOBILITY AND GENE TARGETING

LAMBOWITZ, ALAN M.

UNIVERSITY OF TEXAS AUSTIN

$503,195

5R01GM081635-03

R01

BIOCHEMICAL RECONSTITUTION OF HETEROTRIMERIC G PROTEINS IN THE WNT PATHWAY

LEE, ETHAN

VANDERBILT UNIVERSITY

$233,234

3R01GM081635-03S1

R01

BIOCHEMICAL RECONSTITUTION OF HETEROTRIMERIC G PROTEINS IN THE WNT PATHWAY

LEE, ETHAN

VANDERBILT UNIVERSITY

$59,134

1R01GM082995-01A2

R01

THE ROLE OF THE DNA UNWINDING ELEMENT BINDING PROTEIN, DUE-B, IN DNA REPLICATION

LEFFAK, MICHAEL

WRIGHT STATE UNIVERSITY

$294,145

5R01GM077425-04

R01

BIOELECTRICAL CONTROLS OF MORPHOGENESIS

LEVIN, MICHAEL

TUFTS UNIVERSITY MEDFORD

$245,600

5R01GM078484-03

R01

BIOPHYSICAL CONTROLS OF VERTEBRATE ORGAN REGENERATION

LEVIN, MICHAEL

TUFTS UNIVERSITY MEDFORD

$295,152

5R01GM066953-07

R01

MESODERMAL CELL FATE SPECIFICATION IN C. ELEGANS

LIU, JUN

CORNELL UNIVERSITY ITHACA

$315,837

3R01GM066953-07S2

R01

MESODERMAL CELL FATE SPECIFICATION IN C. ELEGANS

LIU, JUN

CORNELL UNIVERSITY ITHACA

$26,000

5R01GM080673-03

R01

THE ROLE OF AJUBA LIM PROTEIN IN EPITHELIA BIOGENESIS

LONGMORE, GREGORY

WASHINGTON UNIVERSITY

$288,800

5R01GM055560-12

R01

MECHANISMS OF PERMEATION IN INWARD RECTIFIER K+ CHANNELS

LU, ZHE

UNIVERSITY OF PENNSYLVANIA

$373,732

5R01GM061829-10

R01

REGULATION OF CALCIUM SIGNALING DURING OOGENESIS

MACHACA, KHALED

WEILL MEDICAL COLLEGE OF CORNELL UNIV

$214,718

9R01GM088790-05A1

R01

FUNCTIONAL ARCHITECTURE OF IP3-EVOKED LOCAL CA2+ SIGNALS

MARCHANT, JONATHAN S

UNIVERSITY OF MINNESOTA TWIN CITIES

$310,732

3R01GM088790-05A1S1

R01

FUNCTIONAL ARCHITECTURE OF IP3-EVOKED LOCAL CA2+ SIGNALS

MARCHANT, JONATHAN S

UNIVERSITY OF MINNESOTA TWIN CITIES

$224,769

2R01GM067779-05A2

R01

NETWORK-DIRECTED DISCOVERY OF DISEASE GENES

MARCOTTE, EDWARD M

UNIVERSITY OF TEXAS AUSTIN

$273,600

5R01GM063004-08

R01

PROTEIN UNFOLDING IN A PHYSIOLOGICAL SYSTEM

MATOUSCHEK, ANDREAS

NORTHWESTERN UNIVERSITY

$321,695

5R01GM078247-04

R01

BEYOND GFP AND AEQUORIN: OCEAN-WIDE STUDY OF FLUORESCENT AND LUMINOUS PROTEINS

MATZ, MIKHAIL V

UNIVERSITY OF TEXAS AUSTIN

$291,735

5R01GM052112-15

R01

P120-CATENIN SUB-FAMILY FUNCTIONS

MCCREA, PIERRE D

UNIVERSITY OF TEXAS MD ANDERSON CAN CTR

$323,400

3R01GM052112-15S1

R01

P120-CATENIN SUB-FAMILY FUNCTIONS

MCCREA, PIERRE D

UNIVERSITY OF TEXAS MD ANDERSON CAN CTR

$57,411

5R01GM066270-07

R01

MOLECULAR STRUCTURE AND FUNCTION OF THE HUMAN KINETOCHORE OUTER PLATE

MCEWEN, BRUCE F

WADSWORTH CENTER

$367,392

3R01GM066270-07S1

R01

MOLECULAR STRUCTURE AND FUNCTION OF THE HUMAN KINETOCHORE OUTER PLATE

MCEWEN, BRUCE F

WADSWORTH CENTER

$71,546

2R01GM067735-06A1

R01

REPLICATION CHECKPOINT ACTIVATION AND SILENCING

MICHAEL, MATTHEW

HARVARD UNIVERSITY

$335,273

3R01GM067735-06A1S1

R01

REPLICATION CHECKPOINT ACTIVATION AND SILENCING

MICHAEL, MATTHEW

HARVARD UNIVERSITY

$267,145

5R01GM023928-31

R01

CYTOSKELETON POLYMERIZATION DYNAMICS IN THE CELL CYCLE

MITCHISON, TIMOTHY J

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$392,865

5R01GM039565-22

R01

MICROTUBULE DYNAMICS AND MITOTIC MECHANISM

MITCHISON, TIMOTHY J

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$505,486

3R01GM073887-04S1

R01

R01:WNT AND BETA-CATENIN SIGNALING IN REGENERATION

MOON, RANDALL TODD

UNIVERSITY OF WASHINGTON

$126,779

5R01GM050284-12

R01

MITOCHONDRIAL PATHWAYS IN APOPTOSIS

NEWMEYER, DONALD DAVID

LA JOLLA INST FOR ALLERGY & IMMUNOLGY

$340,947

5R01GM078244-03

R01

ELECTROPHYSIOLOGY OF PERIPHERAL NERVE SODIUM CHANNELS

O'LEARY, MICHAEL E

THOMAS JEFFERSON UNIVERSITY

$242,143

3R01GM078244-03S1

R01

ELECTROPHYSIOLOGY OF PERIPHERAL NERVE SODIUM CHANNELS

O'LEARY, MICHAEL E

THOMAS JEFFERSON UNIVERSITY

$25,000

5R01GM083025-02

R01

SPECIFICITY OF EFFECTOR ACTIVATION BY RHO FAMILY GTPASES

PETERSON, JEFFREY R

INSTITUTE FOR CANCER RESEARCH

$314,100

3R01GM083025-02S1

R01

SPECIFICITY OF EFFECTOR ACTIVATION BY RHO FAMILY GTPASES

PETERSON, JEFFREY R

INSTITUTE FOR CANCER RESEARCH

$229,307

1R01GM086526-01A1

R01

SYSTEMS ARCHITECTURE AND DYNAMICAL BEHAVIORS OF THE KINASES THAT DRIVE M-PHASE

POMERENING, JOSEPH RICHARD

INDIANA UNIVERSITY BLOOMINGTON

$269,984

5R01GM059975-09

R01

FUNCTIONAL ANALYSIS OF VERTEBRATE NUCLEAR TRANSPORT

POWERS, MAUREEN A.

EMORY UNIVERSITY

$309,966

5R01GM071760-04

R01

ROLE OF HMGA1 PROTEINS IN DNA DAMAGE AND EXCISION REPAIR

REEVES, RAYMOND

WASHINGTON STATE UNIVERSITY

$275,715

5R01GM046779-19

R01

POLYADENYLATION AND TRANSLATIONAL CONTROL

RICHTER, JOEL D

UNIV OF MASSACHUSETTS MED SCH WORCESTER

$381,875

3R01GM046779-19S1

R01

POLYADENYLATION AND TRANSLATIONAL CONTROL

RICHTER, JOEL D

UNIV OF MASSACHUSETTS MED SCH WORCESTER

$87,135

3R01GM062290-08S1

R01

REGULATION OF INTRACELLULAR TRANSPORT

RODIONOV, VLADIMIR I

UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

$184,773

5R01GM080753-03

R01

FUNCTIONAL ANALYSIS OF THE BIFUNCTIONAL ION CHANNEL AND KINASE TRPM7

RUNNELS, LOREN W

UNIV OF MED/DENT NJ-R W JOHNSON MED SCH

$296,400

3R01GM080753-03S1

R01

FUNCTIONAL ANALYSIS OF THE BIFUNCTIONAL ION CHANNEL AND KINASE TRPM7

RUNNELS, LOREN W

UNIV OF MED/DENT NJ-R W JOHNSON MED SCH

$45,303

3R01GM038277-22S1

R01

HORMONAL REGULATION OF MRNA STABILITY

SCHOENBERG, DANIEL R.

OHIO STATE UNIVERSITY

$123,218

1R01GM079707-01A2

R01

NONSENSE CODON ACTIVATION OF ENDONUCLEASE-MEDIATED MRNA DECAY

SCHOENBERG, DANIEL R.

OHIO STATE UNIVERSITY

$307,500

5R01GM076112-04

R01

BUILDING A SYSTEMS-LEVEL VIEW OF CELL CYCLE CHECKPOINTS

SIBLE, JILL C

VIRGINIA POLYTECHNIC INST AND ST UNIV

$222,162

1R01GM088500-01

R01

REPROGRAMMING CELLS TO ENABLE LIMB REGENERATION

SLACK, JONATHAN M.

UNIVERSITY OF MINNESOTA TWIN CITIES

$302,000

5R01GM030758-28

R01

CENTROSOME REDUPLICATION AND CONSEQUENCES OF CLEAVAGE FAILURE/PROLONGED MITOSIS

SLUDER, GREENFIELD

UNIV OF MASSACHUSETTS MED SCH WORCESTER

$445,734

3R01GM030758-28S2

R01

CENTROSOME REDUPLICATION AND CONSEQUENCES OF CLEAVAGE FAILURE/PROLONGED MITOSIS

SLUDER, GREENFIELD

UNIV OF MASSACHUSETTS MED SCH WORCESTER

$186,599

5R01GM077592-03

R01

METASTASIS-ASSOCIATED KINASE IN WNT SIGNALING

SOKOL, SERGEI Y

MOUNT SINAI SCHOOL OF MEDICINE OF NYU

$318,660

2R01GM052022-14

R01

CENTROSOME STRUCTURE, FUNCTION AND DUPLICATION

STEARNS, TIM

STANFORD UNIVERSITY

$445,803

3R01GM052022-14S1

R01

CENTROSOME STRUCTURE, FUNCTION AND DUPLICATION

STEARNS, TIM

STANFORD UNIVERSITY

$117,773

5R01GM026154-39

R01

SMALL RNP MEDIATORS OF GENE EXPRESSION

STEITZ, JOAN A.

YALE UNIVERSITY

$272,284

3R01GM026154-39S1

R01

SMALL RNP MEDIATORS OF GENE EXPRESSION

STEITZ, JOAN A.

YALE UNIVERSITY

$24,358

5R01GM074728-05

R01

MECHANISMS OF KINETOCHORE ASSEMBLY

STRAIGHT, AARON F

STANFORD UNIVERSITY

$253,404

5R01GM081576-02

R01

MECHANISMS OF "END ON" MICROTUBULE ATTACHMENT BY THE KINETOCHORE

STUKENBERG, P. TODD

UNIVERSITY OF VIRGINIA CHARLOTTESVILLE

$273,948

3R01GM081576-02S1

R01

MECHANISMS OF "END ON" MICROTUBULE ATTACHMENT BY THE KINETOCHORE

STUKENBERG, P. TODD

UNIVERSITY OF VIRGINIA CHARLOTTESVILLE

$99,753

5R01GM076599-04

R01

TRAF4 IN TGF-BETA SIGNALING AND EMBRYONIC DEVELOPMENT

THOMSEN, GERALD H

STATE UNIVERSITY NEW YORK STONY BROOK

$290,606

5R01GM080462-03

R01

REGULATION OF TGF-BETA SIGNALING AND EMBRYONIC DEVELOPMENT BY GTPASES

THOMSEN, GERALD H

STATE UNIVERSITY NEW YORK STONY BROOK

$289,308

3R01GM074096-04S1

R01

MODEL SYNTHETIC CHANNEL ASSEMBLIES

TOMICH, JOHN M

KANSAS STATE UNIVERSITY

$80,136

5R01GM074096-04

R01

MODEL SYNTHETIC CHANNEL ASSEMBLIES

TOMICH, JOHN M

KANSAS STATE UNIVERSITY

$241,955

1R01GM088253-01

R01

THE CONTROL OF CENTRIOLE DUPLICATION AND DEGENERATION

TSOU, MENG-FU BRYAN

SLOAN-KETTERING INSTITUTE FOR CANCER RES

$361,998

2R01GM061275-10

R01

THE NUCLEAR PORE COMPLEX: INTERPHASE AND MITOTIC FUNCTION

ULLMAN, KATHARINE S

UNIVERSITY OF UTAH

$309,093

3R01GM032441-25S1

R01

DNA REPLICATION AND GENE EXPRESSION OF CHLORELLA VIRUSES

VAN ETTEN, JAMES L

UNIVERSITY OF NEBRASKA LINCOLN

$144,281

1F32GM087107-01

F32

BIOELECTRICAL CONTROLS OF LEFT-RIGHT ASYMMETRY

VANDENBERG, LAURA N.

TUFTS UNIVERSITY MEDFORD

$47,210

5R01GM054179-11

R01

MECHANISMS OF GATING AND PERMEATION IN GAP JUNCTIONS

VERSELIS, VYTAUTAS K

ALBERT EINSTEIN COL OF MED YESHIVA UNIV

$319,550

5R01GM074104-05

R01

MECHANISM OF VERTEBRATE NEURAL TUBE MORPHOGENESIS

WALLINGFORD, JOHN B

UNIVERSITY OF TEXAS AUSTIN

$280,998

1R01GM086627-01

R01

DEVELOPMENTAL CONTROL OF CELL POLARITY IN VERTEBRATE EMBRYOS.

WALLINGFORD, JOHN B

UNIVERSITY OF TEXAS AUSTIN

$265,176

5R01GM062267-09

R01

PROPERTIES OF THE EUKARYOTIC REPLICATIVE DNA HELICASE

WALTER, JOHANNES

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$337,398

5R01GM080676-03

R01

CELL CYCLE REGULATION OF VERTEBRATE DNA REPLICATION

WALTER, JOHANNES

HARVARD UNIVERSITY (MEDICAL SCHOOL)

$322,050

5R01GM081489-02

R01

ROLE OF UBP-M AND H2A DEUBIQUITINATION IN CHROMATIN AND CELLULAR FUNCTION

WANG, HENGBIN

UNIVERSITY OF ALABAMA AT BIRMINGHAM

$267,525

3R01GM081489-02S1

R01

ROLE OF UBP-M AND H2A DEUBIQUITINATION IN CHROMATIN AND CELLULAR FUNCTION

WANG, HENGBIN

UNIVERSITY OF ALABAMA AT BIRMINGHAM

$202,813

5F32GM083542-02

F32

MECHANOSENSITIVE SIGNALING AND CELL ADHESION DURING MIGRATION

WEBER, GREGORY

UNIVERSITY OF VIRGINIA CHARLOTTESVILLE

$50,054

5R01GM061671-08

R01

SIGNALING MECHANISMS COORDINATING CELL FATE DETERMINATION AND MORPHOGENESIS

WEINSTEIN, DANIEL

QUEENS COLLEGE

$306,900

5R01GM065232-06

R01

STUDYING THE ROLE OF RAN IN MITOSIS

HEALD, REBECCA W;WEIS, KARSTEN ;

UNIVERSITY OF CALIFORNIA BERKELEY

$327,385

5R01GM072915-04

R01

MECHANISMS OF ENDODERM SPECIFICATION ALONG THE A-P AXIS

WELLS, JAMES M

CHILDREN'S HOSPITAL MED CTR (CINCINNATI)

$276,735

5R01GM057438-11

R01

REGULATION OF NUCLEAR PORE COMPLEX ASSEMBLY

HETZER, MARTIN W;WENTE, SUSAN R. ;

VANDERBILT UNIVERSITY

$459,814

3R01GM050942-13S1

R01

FUNCTION OF 3'UTRS

WICKENS, MARVIN P.

UNIVERSITY OF WISCONSIN MADISON

$473,266

3R01GM073863-04S1

R01

RNA QUALITY CONTROL AND ENVIRONMENTAL STRESS

WOLIN, SANDRA L.

YALE UNIVERSITY

$78,408

5R01GM056238-11

R01

BIOLOGICAL ROLES OF NODAL RELATED GENES IN EMBRYOGENESIS

WRIGHT, CHRISTOPHER V.

VANDERBILT UNIVERSITY

$337,700

2R01GM057962-10A2

R01

WERNER SYNDROME PROTEIN, DNA END PROCESSING, AND DOUBLE-STRAND BREAK REPAIR

YAN, HONG

INSTITUTE FOR CANCER RESEARCH

$388,208

1R01GM085234-01A1

R01

ASSEMBLY OF POLYCYSTIN COMPLEXES

YANG, JIAN

COLUMBIA UNIV NEW YORK MORNINGSIDE

$328,120

3P01GM048677-17S1

P01

ELECTROPHYSIOLOGY & IMAGING CORE

YOSHIKAMI, DOJU

UNIVERSITY OF UTAH

$171,751

5R01GM061542-09

R01

REGULATION OF THE ANAPHASE-PROMOTING COMPLEX BY THE SPINDLE CHECKPOINT

YU, HONGTAO

UNIVERSITY OF TEXAS SW MED CTR/DALLAS

$304,894

3R01GM061542-09S1

R01

REGULATION OF THE ANAPHASE-PROMOTING COMPLEX BY THE SPINDLE CHECKPOINT

YU, HONGTAO

UNIVERSITY OF TEXAS SW MED CTR/DALLAS

$85,000

5R01GM062937-09

R01

SPLICEOSOMAL SNRNA MODIFICATION IN XENOPUS OOCYTES

YU, YI-TAO

UNIVERSITY OF ROCHESTER

$272,657

5R01GM084879-02

R01

EVOLUTION OF SODIUM CHANNEL GENES

ZAKON, HAROLD H

UNIVERSITY OF TEXAS AUSTIN

$296,800

3R01GM084879-02S1

R01

EVOLUTION OF SODIUM CHANNEL GENES

ZAKON, HAROLD H

UNIVERSITY OF TEXAS AUSTIN

$271,398

5R01GM083889-13

R01

MECHANISMS OF GROWTH CONE TURNING IN DIFFUSIBLE GRADIENT

ZHENG, JAMES Q

EMORY UNIVERSITY

$341,000

5R01GM084363-02

R01

DIRECTED GROWTH CONE MIGRATION BY CALCIUM SIGNALS

ZHENG, JAMES Q

EMORY UNIVERSITY

$262,880

3R01GM084363-02S1

R01

DIRECTED GROWTH CONE MIGRATION BY CALCIUM SIGNALS

ZHENG, JAMES Q

EMORY UNIVERSITY

$60,000

5R01GM081492-03

R01

MECHANISMS OF DIFFERENT WNT SIGNALS

ZHENG, JIE J.

ST. JUDE CHILDREN'S RESEARCH HOSPITAL

$310,800

5P01GM047969-18

P01

PHYSIOLOGICAL STUDIES OF NEUROSTEROID ANALOGUES

ZORUMSKI, CHARLES F

WASHINGTON UNIVERSITY

$348,917

����������������������������������������������������������������������������������������������� Total: ������������ $43,883,452