Stem Cell Mechanism In The Murine Germline
Haifan Lin, Professor
Duke University 2200 W. Main St. Durham, Nc 27705
Grant 1R01HD042012-01 from National Institute Of Child Health And Human Development IRG: ZRG1
Abstract: Our long term goal is to learn how the self-renewal of stem cells is achieved and regulated, a question crucial to understanding tissue development, oncogenesis, wound repair, immunodeficiency, and infertility. Our focus is to study stem cells in the germline. In so doing, we hope to link our research between two extremely important yet highly enigmatic areas of biomedical research - germline and stem cell biology. Our approach is to establish Drosophila as a pilot system to explore molecular mechanisms underlying stem cell division, and to expand what we learn from Drosophila to mammalian systems via the reverse genetics approach. Specifically, we have identified germline stem cells in Drosophila and discovered key genes that control the intra- and intercellular mechanisms of the stem cell division. Further more, we have been intensively studying these genes in mammalian systems. This strategy has offered us unparalleled opportunities to discover fundamental stem cell mechanisms and to explore their medical significance. Our hypothesis is that the function of key stem cell genes is conserved during evolution. In support of this, we have discovered the first and only known family of evolutionarily conserved genes, the piwi family genes that are involved in stem cell self-renewal in diverse organisms in animal and plant kingdoms. Our working hypothesis in this proposal is that two murine members of this gene family, miwi and mili, are involved in cell-autonomous mechanisms that control spermatogonial stem cell division and spermatogenesis. Our specific aim in this proposal is to explore the stem cell mechanism by systematically characterizing the function of miwi and miii in spermatogonial stem cell division and its related processes. With all the tools in place and experience in most of the proposed analyses, we plan to 1. Characterize mili expression during germline development. 2. Analyze the developmental function of miii by creating and examining conditional mili-null mice. 3. Characterize the roles of miwi and mili in spermatogonial stem cell division. 4. Analyze the biochemical roles of MIWI and MILl in spermatogonial stem cell division. 5. Identify direct target genes of MIWI and MILl to further study MIWI/MILI-mediated mechanisms.
Keywords: cell biology, spermatogenesis, stem cell, cell growth regulation, developmental genetics, endoplasmic reticulum, Drosophilidae, gene targeting, green fluorescent protein, laboratory mouse
Project start date: 2002-04-01
Project end date: 2007-03-31
1R01HD042012-01 (2002): $311850
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Haifan Lin
REGULATION OF GERMLINE STEM CELL DIVISION IN DROSOPHILA
Haifan Lin, Professor
Duke University 2200 W. Main St. Durham, Nc 27705
Grant 5R01HD033760-04 from National Institute Of Child Health And Human Development IRG: GEN
Abstract: The investigator is interested in how the self renewing asymmetric division of stem cells is achieved and regulated. He is using the female germ line of Drosophila as a model system to study this problem. As a postdoctoral fellow with Allan Spradling the PI developed an in vivo culture system for the germ line stem cells which are located near the end of the germarium. He combined this with laser ablation to show that each germarium contained 2-3 stem cells that are in contact with somatic cells that form the terminal filament. He identified a novel "organelle" that he named the spectrosome that contained both spectrin and the adducin like protein product of the hts gene. The spectrosome is located between the stem cell nuclei and the terminal filament. During mitosis the spectrosome remains next to the terminal filament. Following centriole duplication one centriole stays near the spectrosome, and one aster and one pole of the mitotic spindle becomes associated with the spectrosome. The asymmetric association of the spectrosome with the mitotic spindle reveals the asymmetry of the stem cell division. The hts mutation results in a loss of the spectrosome and abnormal egg chamber development. In other experiments the PI found that ablation of terminal filament cells resulted in increased cell division of the stem cells suggesting that the terminal filament cells regulated cell proliferation of the stem cells. The PI further identified a number of enhancer traps that are expressed in the cells of the anterior region of the germarium and he obtained evidence that a number of segment polarity genes such as hh, wg and en are involved in regulating development of the egg chamber. Finally the PI identified two genes defined by P insertions that appear to be essential for the asymmetric division of the stem cells. One of these, ovarette (ovt), results in ovarioles mostly with two-three clusters of germ line cells that appear similar to one another. There is no evidence for differentiation. However, a small number of ovariole contain only two-three mature eggs but no other germ cells. The PI interprets this as suggesting that the mutation prevents the asymmetric division of the stem cells. The second gene is called piwi. Mutations in this gene result in ovarioles with two or fewer developing egg chambers. The PI suggests that this mutation results in a failure of the stem cells to be maintained in an undifferentiated state (i.e., they lose the quality of stemness). There are 5 specific aims proposed. The first is to systematically examine the role of the various somatic cells in regulating stem cell division. A photochemical activation ablation method will be used to ablate different sets of somatic cells located at the anterior end of the germaria. The ablated germaria would then be cultured in vivo to assay the stem cells. The second specific aim is to examine the stem cell division in the absence of the spectrosome. This will be done by examining hts mutant germaria via confocal microscopy. The third specific aim is to define the role of ovt and piwi in the somatic induction mechanism. The PI will use pole cell transplantation to generate genetic mosaics to determine whether the mutations act in the germ line or soma. The PI will also examine the expression of these two genes at both the RNA and protein level. Of particular interest is which cells express each of the genes. The fourth specific aim is to analyze the molecular structure of these two genes and to determine the nature of their protein products. The final specific aim is to analyze the cellular behavior of the two proteins.
Keywords: cell cycle, cell growth regulation, cell population study, germ cell, gene expression, Drosophilidae, cell transplantation, confocal scanning microscopy, female
Project start date: 1996-02-01
Project end date: 2000-01-31
5R01HD033760-04 (1999): $265913
5R01HD033760-03 (1998): $254139
5R01HD033760-02 (1997): $207369
FUNCTION OF PIWI/ARGONUATE PROTEINS IN SPERMATOGENESIS
Haifan Lin, Professor Of Cell Biology
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5R01HD042012-09 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Piwi/Argonaute (Ago) is the only known protein family with function in stem cell self-renewal highly conserved in both animal and plant kingdoms. These proteins also play key roles in germline development and RNAi/miRNA-mediated mechanisms. Our long term goal is to learn molecular mechanisms mediated by the Piwi/Ago proteins in regulating spermatogenesis. This will also contribute to understanding of stem cell division and other developmental processes mediated by this family of proteins. Our strategy has been to use Drosophila as a model to study these proteins in gametogenesis, and then to further what we learn from Drosophila to mammalian and clinical settings. Particularly, in the current funding period, we have demonstrated that mili, a murine member of the gene family, is essential for spermatogonial stem cell division and meiosis, yet miwi, another member, is a key regulator of spermiogenesis. These represent the first two in vivo studies of the piwi/ago gene family in mammalian systems. Moreover, we have shown that the overexpression of a human piwi gene, hiwi, is highly correlated to testicular seminomas. Our specific aim here is to study the molecular mechanisms through which mili and miwi regulate spermatogenesis. Piwi/Ago family proteins are known to negatively regulate gene expression via RNAi, miRNA, and epigenetic pathways. Our latest studies, however, indicate that miwi and mili positively regulate translation and stability of target mRNAs, possibly via a miRNA-mediated mechanism. These findings provide an unparalleled opportunity for us to discover a novel mechanism of gene regulation that is fundamental to reproductive and stem cell biology. Our working hypothesis has three components First, Mili and Miwi bind to and stabilize target mRNAs required for their target spermatogenic events; second, this function is coupled to translational regulation; third, this function is mediated by miRNAs. To test this hypothesis, we propose to (1) systematically identify target mRNAs of Mili and Miwi. (2) Characterize the effect of Mili and Miwi binding on the stability of target mRNAs. (3) Determine if Mili and Miwi controls the stability of target mRNAs by regulating their translation. (4) Identify Mili/Miwi-target miRNAs and determine their function in regulating mRNA. Because Piwi/Ago proteins have demonstrated roles in oncogenesis, the proposed studies should bear significant health implications
Keywords: Animals; Assay; Bears; Binding; Binding (Molecular Function); Bioassay; Biologic Assays; Biological Assay; Biological Function; Biological Models; Biological Process; Clinical; Co-Immunoprecipitations; Complex; Coupled; Development; Developmental Process; Drosophila; Drosophila genus; Epigenetic; Epigenetic Change; Epigenetic Mechanism; Epigenetic Process; Event; Fruit Fly, Drosophila; Funding; Gametogenesis; Gene Action Regulation; Gene Expression; Gene Expression Regulation; Gene Family; Gene Regulation; Gene Regulation Process; Genes; Genital System, Male, Testis; Goals; Half-Life; Half-Lifes; Health; Human; Human, General; In Situ; Learning; Mammalia; Mammals; Mammals, General; Mammals, Mice; Man (Taxonomy); Man, Modern; Measures; Mediating; Meiosis; Messenger RNA; Methods; Mice; Micro RNA; MicroRNAs; Model System; Modeling; Models, Biologic; Molecular; Molecular Interaction; Mother Cells; Murine; Mus; Oncogenesis; Pathway interactions; Plants; Plants, General; Play; Polyribosomes; Polysomes; Post-Transcriptional Gene Silencing; Post-Transcriptional Gene Silencings; Posttranscriptional Gene Silencing; Posttranscriptional Gene Silencings; Process; Progenitor Cells; Protein Family; Proteins; Quelling; RNA Interference; RNA Silencing; RNA Silencings; RNA, Messenger; RNAi; Regulation; Role; Seminoma of the Testis; Sequence-Specific Posttranscriptional Gene Silencing; Spermatogenesis; Spermiogenesis; Stability, mRNA; Staging; Stem cells; System; System, LOINC Axis 4; Testicles; Testicular Seminoma; Testicular Seminoma Pure; Testing; Testis; Translational Regulation; Translations; Ursidae; Ursidae Family; Work; base; cDNA Arrays; cDNA Microarray; experiment; experimental research; experimental study; fruit fly; gene product; in vivo; mRNA; mRNA Stability; meiotic; member; miRNA; mutant; novel; overexpression; pathway; reproductive; research study; self-renewal; social role; stem cell biology; stem cell division; tumorigenesis
Project start date: 2002-04-01
Project end date: 2012-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
5R01HD042012-09 (2010): $321136
REGULATION OF GERMLINE STEM CELL DIVISION IN DROSOPHILA
Haifan Lin, Professor
Duke University 2200 W. Main St. Durham, Nc 27705
Grant 5R01HD033760-09 from National Institute Of Child Health And Human Development IRG: GEN
Abstract: Our long term goal is to learn how the self-renewing asymmetric division of stem cells is achieved, a question crucial to the understanding of tissue development/repair, oncogenesis, immunodeficiency, and sterility. Our focus has been to address this question in Drosophila germline stem cells, initially by identifying these cells and revealing the self-renewing asymmetry of their division, followed by genetic dissection of the underlying mechanism. This leads to the finding of piwi, Yb, pumilio (pum), and arrest (aret) genes essential for germline stem cell renewal. Our working hypothesis is that the self- renewing ability of germ-line stem cells is induced by signaling from Yb/piwi/hh-expressing apical somatic cells. The somatic induction is achieved by controlling the asymmetric distribution of key proteins between the stem cell and its differentiated daughter, the cystoblast, which renders their specific fates. Such key proteins include PUM which regulates differential translation, BAM which promotes cystoblast differentiation and PIWI which is also expressed in the germline as a cell-autonomous promoter of stem cell division. Our specific aims are to explore the stem cell mechanism by systematically testing and expanding this hypothesis. With all the tools in place and experience in most of the following analyses, we propose to 1. Analyze the biochemical role of PIWI as a nuclear factor in germline stem cell division. 2. Examine the developmental role of Yb in signaling germline stem cell division. 3. Analyze the biochemical role of YB in signaling cells. 4. Define regulatory relationship between genes involved in producing somatic signals. 5. Identify new genes interacting with piwi by genetic suppressor screens.
Keywords: cell cycle, cell growth regulation, germ cell, oogenesis, stem cell, biological signal transduction, cell population study, gene expression, transcription factor, Drosophilidae, female, laboratory rabbit
Project start date: 1996-02-01
Project end date: 2005-12-31
5R01HD033760-09 (2004): $363063
5R01HD033760-08 (2003): $352488
5R01HD033760-07 (2002): $342222
5R01HD033760-06 (2001): $332255
2R01HD033760-05 (2000): $322576
Sponsored Links Excellgen http://Excellgen.com
3R01HD033760-10A1S1 (2006): $116438
Stem Cell Mechanism In The Murine Germline
Haifan Lin, Professor
Duke University 2200 W. Main St. Durham, Nc 27705
Grant 5R01HD042012-04 from National Institute Of Child Health And Human Development IRG: ZRG1
Abstract: Our long term goal is to learn how the self-renewal of stem cells is achieved and regulated, a question crucial to understanding tissue development, oncogenesis, wound repair, immunodeficiency, and infertility. Our focus is to study stem cells in the germline. In so doing, we hope to link our research between two extremely important yet highly enigmatic areas of biomedical research - germline and stem cell biology. Our approach is to establish Drosophila as a pilot system to explore molecular mechanisms underlying stem cell division, and to expand what we learn from Drosophila to mammalian systems via the reverse genetics approach. Specifically, we have identified germline stem cells in Drosophila and discovered key genes that control the intra- and intercellular mechanisms of the stem cell division. Further more, we have been intensively studying these genes in mammalian systems. This strategy has offered us unparalleled opportunities to discover fundamental stem cell mechanisms and to explore their medical significance. Our hypothesis is that the function of key stem cell genes is conserved during evolution. In support of this, we have discovered the first and only known family of evolutionarily conserved genes, the piwi family genes that are involved in stem cell self-renewal in diverse organisms in animal and plant kingdoms. Our working hypothesis in this proposal is that two murine members of this gene family, miwi and mili, are involved in cell-autonomous mechanisms that control spermatogonial stem cell division and spermatogenesis. Our specific aim in this proposal is to explore the stem cell mechanism by systematically characterizing the function of miwi and miii in spermatogonial stem cell division and its related processes. With all the tools in place and experience in most of the proposed analyses, we plan to 1. Characterize mili expression during germline development. 2. Analyze the developmental function of miii by creating and examining conditional mili-null mice. 3. Characterize the roles of miwi and mili in spermatogonial stem cell division. 4. Analyze the biochemical roles of MIWI and MILl in spermatogonial stem cell division. 5. Identify direct target genes of MIWI and MILl to further study MIWI/MILI-mediated mechanisms.
Keywords: cell biology, spermatogenesis, stem cell, cell growth regulation, developmental genetics, endoplasmic reticulum, Drosophilidae, gene targeting, green fluorescent protein, laboratory mouse
Project start date: 2002-04-01
Project end date: 2007-03-31
5R01HD042012-04 (2005): $311850
5R01HD042012-03 (2004): $311850
5R01HD042012-02 (2003): $311850
REGULATION OF GERMLINE STEM CELL DIVISION IN DROSOPHILA
Haifan Lin, Professor Of Cell Biology
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 5R01HD033760-15 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Our goal is to learn how the self-renewing ability of stem cells is achieved?a question central to the understanding of tissue development, maintenance, and repair, with profound implications in regenerative medicine and cancer treatment. Our strategy is to use Drosophila as a model to address this question, and to extend what we learn from Drosophila to mammalian and clinical settings. We previously identified germline stem cells (GSCs) in Drosophila and revealed the self-renewing pattern of their divisions. We then discovered key genes that define inter- and intracellular mechanisms of stem cell division, and demonstrated the essential role of intercellular signaling in GSC maintenance. This has led to the development of the current stem cell niche theory. Moreover, our studies of the piwi (a.k.a., argonaute) family genes, the only known family of genes with stem cell function highly conserved in both animal and plant kingdoms, start to link epigenetic regulation to stem cell function. Our focus will be on how epigenetic mechanisms dictate stem cell fate. We will investigate what regulates changes of chromatin organization and activity to generate the unique gene expression profile of the genome that defines stem cell fate. Specifically, we are in a unique position to study epigenetic program-ing mediated by PIWI family proteins and small RNAs?an exciting new frontier of stem cell research. Our working hypothesis is that PIWI controls stem cell fate by regulating the transcriptional activity of the chromatin via heterochromatin protein 1 (HP1) and small RNA-mediated processes. This regulation can occur in stem cells or niche cells. To test and to further develop this hypothesis, we propose to 1. Test the fundamental hypothesis that epigenetic programming determines stem cell fate. 2. Define and characterize the functional domains of PIWI. 3. Identify PlWI-interacting proteins and characterize their potential epigenetic function in the stem/niche cell genomes. 4. Identify the small RNA targets of PIWI and characterize their function in the epigenetic regulation of stem and niche cell genomes
Keywords: 3-D structure; 3-dimensional structure; 3D structure; Address; Animals; Biochemical; Biological Function; Biological Process; Body Tissues; Cancer Treatment; Cell Communication and Signaling; Cell Function; Cell Growth and Maintenance; Cell Maintenance; Cell Process; Cell Signaling; Cell physiology; Cells; Cellular Function; Cellular Physiology; Cellular Process; Chromatin; Clinical; Co-Immunoprecipitations; Collaborations; Development; Drosophila; Drosophila genus; Epigenetic; Epigenetic Change; Epigenetic Mechanism; Epigenetic Process; Expression Profiling; Expression Signature; Family; Fruit Fly, Drosophila; Gene Action Regulation; Gene Expression Profile; Gene Expression Regulation; Gene Family; Gene Regulation; Gene Regulation Process; Genes; Genetics-Mutagenesis; Genome; Genomics; Goals; HP-1 protein; Individual; Intracellular Communication and Signaling; Investigators; Learning; Link; Maintenance; Maintenances; Malignant Neoplasm Therapy; Malignant Neoplasm Treatment; Mediating; Modeling; Molecular Biology, Mutagenesis; Molecular Fingerprinting; Molecular Genetic; Molecular Genetics; Molecular Profiling; Mother Cells; Mutagenesis; N-terminal; NH2-terminal; Pattern; Plants; Plants, General; Play; Position; Positioning Attribute; Process; Progenitor Cells; Programs (PT); Programs [Publication Type]; Protein Binding; Protein Family; Proteins; Proteomics; Regenerative Medicine; Regulation; Research Personnel; Researchers; Role; Signal Transduction; Signal Transduction Systems; Signaling; Small RNA; Stem Cell Research; Stem cells; Subcellular Process; Testing; Tissues; Two Hybrid; Work; Yeast One Hybrid System; Yeast One/Two-Hybrid System; Yeasts; anticancer therapy; base; biological signal transduction; cancer therapy; frontier; fruit fly; gene expression signature; gene product; heterochromatin protein 1; heterochromatin-specific nonhistone chromosomal protein HP-1; in vivo; molecuar profile; molecular domain; molecular signature; programs; repair; repaired; self-renewal; social role; stem cell division; stem cell fate; stem cell niche; theories; three dimensional structure; transcriptome; yeast two hybrid system
Project start date: 1996-02-01
Project end date: 2010-12-31
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
5R01HD033760-15 (2010): $311824
5R01HD033760-12 (2007): $320916
2R01HD033760-10A1 (2006): $310500
TOWARD A CENTRAL QUESTION IN EPIGENETICS: A MAJOR EPIGENETIC PROGRAMMING MECHANIS
Haifan Lin
Yale University, 47 College Street, Ste 203, New Haven, Ct 06520-8047
Grant 1DP1OD006825-01 from Office Of The Director, National Institutes Of Health
Abstract: Epigenetics represents an exciting new frontier of biomedical research. A central yet essentially unexplored question in epigenetics is how epigenetic regulators are directed to specific loci in the genome to exert their function. It is known that a few transcriptional factors can recruit certain epigenetic factors to the promoters of target genes. However, this mechanism so far can only account for a handful of genes, and a tiny fraction of the genome. The latest Drosophila work in my lab suggest that PIWI-interacting RNAs (piRNAs) play a major and direct role in guiding epigenetic factors to many sites in the genome. Particularly, piRNA form complexes with PIWI proteins and directly bind to piRNA-complementary sites in the genome to regulate their epigenetic state. Furthermore, we have shown that PIWI directly recruits a key epigenetic factor called Heterochromatin Protein 1a to these sites. Based on these results, we propose a "Piwi-piRNA guidance hypothesis", in which the Piwi-piRNA complex serves as a sequence- recognition machinery that recruits epigenetic effectors to specific genomic sites to execute epigenetic regulation. Here we propose to use combined genetic and genomic approaches to systematically test this hypothesis and to determine the contribution of the PIWI-piRNA- mediated mechanism to the genome at 10-basepair resolution. Specifically, we propose to (1) Create the first functional epigenome map to determine the specific epigenetic effect of PIWI towards different regions of the genome; (2) develop a genome-wide epigenetic assay to examine the sufficiency and direct role of PIWI in regulating the transcriptional state of chromatin; and (3) take a four-pronged approach to directly test the role of piRNAs in guiding epigenetic factors to their sites. The proposed study should reveal a fascinating dimension of epigenetic regulation and generate a potentially transformative impact to the broad fields of epigenetics, genetics, molecular, develo
Keywords: Accounting; Assay; Binding; Binding (Molecular Function); Bioassay; Biologic Assays; Biological Assay; Biomedical Research; Chromatin; Complex; Development; Dimensions; Drosophila; Drosophila genus; Epigenetic; Epigenetic Change; Epigenetic Mechanism; Epigenetic Process; Fruit Fly, Drosophila; Gene Targeting; Genes; Genetic; Genome; Genomics; Heterochromatin; Maps; Mediating; Molecular Genetic; Molecular Genetics; Molecular Interaction; Play; Programs (PT); Programs [Publication Type]; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Proteins; Recruitment Activity; Regulation; Resolution; Role; Site; Targetings, Gene; Testing; Work; ing; base; fascinate; frontier; fruit fly; gene product; genome-wide; piRNA; programs; recruit; social role; stem cell biology
Project start date: 2010-09-30
Project end date: 2015-07-31
Budget start date: 30-SEP-2010
Budget end date: 31-JUL-2011
PFA/PA: RFA-RM-09-010
1DP1OD006825-01 (2010): $827500
Sponsored Links Excellgen http://Excellgen.com
Function Of PIWI/Argonuate Proteins In Spermatogenesis
Haifan Lin, Professor
Cell Biologyyale University, 47 College Street, Ste 203, New Haven, Ct 065208047
Grant 2R01HD042012-06A1 from National Institute Of Child Health And Human Development IRG: CMIR
Abstract: DESCRIPTION () Piwi/Argonaute (Ago) is the only known protein family with function in stem cell self-renewal highly conserved in both animal and plant kingdoms. These proteins also play key roles in germline development and RNAi/miRNA-mediated mechanisms. Our long term goal is to learn molecular mechanisms mediated by the Piwi/Ago proteins in regulating spermatogenesis. This will also contribute to understanding of stem cell division and other developmental processes mediated by this family of proteins. Our strategy has been to use Drosophila as a model to study these proteins in gametogenesis, and then to further what we learn from Drosophila to mammalian and clinical settings. Particularly, in the current funding period, we have demonstrated that mili, a murine member of the gene family, is essential for spermatogonial stem cell division and meiosis, yet miwi, another member, is a key regulator of spermiogenesis. These represent the first two in vivo studies of the piwi/ago gene family in mammalian systems. Moreover, we have shown that the overexpression of a human piwi gene, hiwi, is highly correlated to testicular seminomas. Our specific aim here is to study the molecular mechanisms through which mili and miwi regulate spermatogenesis. Piwi/Ago family proteins are known to negatively regulate gene expression via RNAi, miRNA, and epigenetic pathways. Our latest studies, however, indicate that miwi and mili positively regulate translation and stability of target mRNAs, possibly via a miRNA-mediated mechanism. These findings provide an unparalleled opportunity for us to discover a novel mechanism of gene regulation that is fundamental to reproductive and stem cell biology. Our working hypothesis has three components First, Mili and Miwi bind to and stabilize target mRNAs required for their target spermatogenic events; second, this function is coupled to translational regulation; third, this function is mediated by miRNAs. To test this hypothesis, we propose to (1) systematically identify target mRNAs of Mili and Miwi. (2) Characterize the effect of Mili and Miwi binding on the stability of target mRNAs. (3) Determine if Mili and Miwi controls the stability of target mRNAs by regulating their translation. (4) Identify Mili/Miwi-target miRNAs and determine their function in regulating mRNA. Because Piwi/Ago proteins have demonstrated roles in oncogenesis, the proposed studies should bear significant health implications.
Project start date: 2002-04-01
Project end date: 2012-02-29
2R01HD042012-06A1 (2007): $330000
3R01HD042012-09S1 (2010): $89383
REGULATION OF GERMLINE STEM CELL DIVISION IN DROSOPHILA
Haifan Lin, Professor
Duke University 2200 W. Main St. Durham, Nc 27705
Grant 1R01HD033760-01 from National Institute Of Child Health And Human Development IRG: GEN
Project start date: 1996-02-01
Project end date: 2000-01-31
1R01HD033760-01 (1996): $199393