Richard M Harland
University Of California Berkeley
Project start date: 1988-09-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
GENE EXPRESSION IN AMPHIBIAN DEVELOPMENT
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM042341-14 from National Institute Of General Medical Sciences IRG: CBY
Abstract: The ultimate objective of the work in my laboratory is to understand the early development of vertebrates at the molecular level. Our approaches include the isolation of genes that play a critical role, analysis of their expression and function, and examination of the mechanisms whereby patterns of gene expression are altered in early development. We have chosen to study this problem primarily in Xenopus because the embryos are large and easy to manipulate surgically, and the function of macromolecules, such as mRNA or protein, can be assayed by injection into living embryos. Furthermore, the stages of development when the dorso- ventral and antero-posterior axes form are readily accessible to biochemical and embryological analysis. In the next five years we will have two major objectives first we will study the molecules that induce and pattern the mesoderm before and during gastrulation. Second, we will determine the molecular basis for neural induction and neural patterning. To carry out these aims we will clone peptide growth factors and signal transduction components that are used in embryonic patterning. Molecules that are used in early embryogenesis are reused, often for different purposes, later in development. Thus, increasing our understanding of early development will aid in understanding and treating diseases of the adult.
Keywords: developmental genetics, early embryonic stage, gene expression, genetic regulation, histogenesis, homeobox gene, vertebrate embryology, biological signal transduction, genetic transcription, genetic translation, growth factor, posttranscriptional RNA processing, protein structure /function, Xenopus, endonuclease, genetic manipulation, in situ hybridization, laboratory mouse, laboratory rabbit, microinjection, molecular cloning, nucleic acid sequence, polymerase chain reaction, tissue /cell culture
Project start date: 1988-09-01
Project end date: 1999-12-02
5R01GM042341-14 (1998): $306886
5R01GM042341-13 (1997): $295256
5R01GM042341-10 (1994): $261028
5R01GM042341-09 (1993): $248573
5R01GM042341-08 (1992): $253881
5R01GM042341-21 (2007): $337526
Gene Expression In Amphibian Devlopement
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM042341-20 from National Institute Of General Medical Sciences IRG: ZRG1
Abstract: Our long-term goal is to understand the signals that pattern the early vertebrate embryo. We study this problem predominantly in the frog Xenopus laevis. This animal produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. Many of the paradigms for early developmental mechanisms in vertebrates have come from work with amphibians, and many of the signaling activities that bring about early developmental decisions in vertebrates have been identified first in amphibians. During previous grant periods, we have identified signals that act in early axis formation, mesoderm patterning and neural induction. In conjunction with the work of many other groups, this has led to a coherent picture of how the embryonic axes are established, and how a cascade of signal transductions leads to the elaborate pattern of the gastrula. Despite the progress that has been made in understanding embryonic signals, there is still only a partial picture of how the detailed pattern of the embryo emerges. The intracellular mediation of signaling is poorly understood, and although the main pathways that signal in development have been identified, the precise roles and modulation of these pathways remains to be determined. The formation of the neural plate with its elaborate patterning in both anterior-posterior and mediolateral axes poses a particular challenge, and this proposal will examine the integration of signaling pathways that induce and pattern the neural plate. Particular focus will be given to Fibroblast Growth Factor signaling in neural patterning, and in neural crest formation. The integration of signals that induce the neural crest will be studied by exploiting and comparing various manipulations that bring about neural crest development.
Keywords: biological signal transduction, developmental genetics, early embryonic stage, fibroblast growth factor, gene expression, histogenesis, neural crest, vertebrate embryology, ectoderm, embryogenic cleavage, homeobox gene, mesoderm, neural plate /tube, Xenopus, genetic manipulation, microinjection, microsurgery, molecular cloning, tissue /cell culture
Project start date: 1988-09-01
Project end date: 2009-01-31
5R01GM042341-20 (2006): $348390
GENE EXPRESSION IN AMPHIBIAN DEVELOPMENT
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM042341-18 from National Institute Of General Medical Sciences IRG: CDF
Abstract: Our long term goal is to understand the signals that pattern the early vertebrate embryo. We study this problem predominantly in the frog Xenopus laevis. This animal produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. Despite the progress that has been made in understanding embryonic signals, there is still only a partial picture of how the detailed pattern of the embryo emerges. The main hypothesis driving work in the next grant period is that there are a substantial number of embryonic signaling activities that remain to be identified. We will identify these signals so that they can be further understood at the embryological and molecular level. In the next grant period, there are three general areas that will be pursued We will study signals from the neural plate that influence mesodermal and neural fates. We will further dissect the wnt signal transduction pathway that leads to early events of axis formation, and sensitization of the ectoderm to neuralizing signals. Finally, we will use our proven expression cloning techniques to isolate and study molecules that influence mesodermal and neural pattern. Many of the same cellular mechanisms are used in embryos and in adults; therefore an increased understanding of the basic biology of development will improve our understanding of human development and physiology.
Keywords: biological signal transduction, developmental genetics, early embryonic stage, gene expression, histogenesis, vertebrate embryology, ectoderm, embryogenic cleavage, homeobox gene, mesoderm, neural plate /tube, Xenopus, genetic manipulation, laboratory mouse, laboratory rabbit, microinjection, microsurgery, molecular cloning, tissue /cell culture
Project start date: 1988-09-01
Project end date: 2005-01-31
5R01GM042341-18 (2003): $337913
Sponsored Links Excellgen http://Excellgen.com
5R01GM042341-17 (2002): $329497
5R01GM042341-16 (2001): $327425
5R01GM042341-24 (2010): $359720
5R01GM042341-12 (1996): $286207
Grants awarded to Richard M Harland
AXIS FORMATION IN VERTEBRATE DEVELOPMENT
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM049346-03 from National Institute Of General Medical Sciences IRG: CBY
Abstract: Towards the long term aim of understanding vertebrate development at the molecular level, the immediate objective of this work is to understand the function and activities of a newly identified gene. The noggin gene was identified in a functional screen for molecules which induce a dorsal-ventral axis in the amphibian Xenopus. The gene is expressed in parts of the embryo which have dorsal organizing activity, including the Spemann organizer. The gene encodes a novel secreted polypeptide whose function will be investigated at several levels. First we will express and purify the protein; purified protein will be used to study the properties of the polypeptide and will be used as a ligand to isolate the receptor for noggin. The properties of the receptor and the second messenger pathway that it activates in the target cell will be studied. In the second part of the project the role of the noggin gene in normal development of vertebrates will be determined. Dominant negative mutations in the noggin ligand or receptor will be made and tested. the mutant will be reintroduced into embryos as messenger RNA to study the consequences of disrupting noggin function. To test the generality of importance of the noggin gene a mouse noggin homolog, which shares extensive sequence identity with the frog gene, will be used to test the similarity of expression, and will be used to disrupt the mouse gene in order to study the developmental consequences of a null allele. In the third part of the project the biological activities of noggin protein will be tested. Is noggin responsible for the activities of the Spemann organizer, including neural induction? The possibility that noggin has effects on growth or differentiation of cells in the differentiated animal is suggested by the late pattern of expression in skeletal, neural and mesenchymal tissues. Other growth factors that are active in early development (fibroblast growth factor and activin) have distinct roles in later growth and differentiation. The biological effects of noggin on specific target tissues will be tested with a particular view towards identifying any useful therapeutic possibilities in human disease. These may include use as a growth factor for tissue culture, use as a growth or differentiation factor in wound healing, or use as a trophic factor in degenerative diseases.
Keywords: developmental genetics, gene expression, histogenesis, mammalian embryology, protein structure function, alternatives to animals in research, binding protein, chemical binding, gene mutation, genetic regulation, protein purification, receptor binding, second messenger, RNase protection assay, SDS polyacrylamide gel electrophoresis, Xenopus, immunoprecipitation, in situ hybridization, molecular cloning, northern blotting, nucleic acid sequence, western blotting
Project start date: 1993-05-01
Project end date: 1997-04-30
5R01GM049346-03 (1995): $179837
5R01GM049346-02 (1994): $167171
1R01GM049346-01 (1993): $181322
Genetic Analysis Of Silurana Tropicalis Development
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM066684-04 from National Institute Of General Medical Sciences IRG: ZRG1
Abstract: To pursue the aims of this Request For Applications" we will assess the utility of Silurana (Xenopus) tropicalis for standard genetic manipulations. To date, a limited number of organisms have been exploited for forward genetic analysis. However, it has become clear that different organisms have different strengths. Our main goal in this proposal is to establish methods that will test the utility of Silurana tropicalis as an additional useful organism for genetic manipulation. A good theoretical rationale has been established, namely that the animal has a relatively short life cycle, and is relatively easy to raise in a lab setting. The embryos develop externally, and in enormous numbers, so are available for screens of early developmental defects. S. tropicalis is a tetrapod, more closely related to humans than is the fish, and therefore more useful for examination of processes such as limb development. By comparison with Xenopus laevis, a pseudotetraploid, S. tropicalis appears not to have undergone either complete or partial genome duplications, so we do not expect multiple genes to have overlapping and therefore redundant functions. In addition, the kinds of embryological experiments that can be done in Xenopus are sufficiently different from those that can be done in the fish, that the use of mutant animals will provide new information about cell and tissue interactions. We will carry out a genetic screen, map deletions cytologically, and optimize insertional mutagenesis.
Keywords: Xenopus, disease /disorder model, gene expression, genetic manipulation, genetic screening, genetic technique, model design /development, cytology, developmental disease /disorder, gene mutation, biotechnology, gamma radiation, gene targeting, genetic mapping, in situ hybridization, nucleic acid sequence, polymerase chain reaction, transposon /insertion element
Project start date: 2002-04-01
Project end date: 2006-03-31
5R01GM066684-04 (2005): $298124
5R01GM066684-03 (2004): $298362
5R01GM066684-02 (2003): $289304
1R01GM066684-01 (2002): $322721
GENETIC ANALYSIS OF INNER EAR DEVELOPMENT IN TROPICALIS
Richard M Harland
University Of California Berkeley, 2150 Shattuck Avenue, Room 313, Berkeley, Ca 94704-5940
Grant 5R21DC010210-02 from National Institute On Deafness And Other Communication Disorders
Abstract: To advance our understanding of ear development and the underlying molecular and genetic interactions, we are undertaking a forward genetic screen in the amphibian Xenopus tropicalis, a recently introduced genetic model animal. This pilot study reveals several loci involved in ear morphology, otolith formation, and balancing/swimming behavior. Importantly, the major events of X. tropicalis ear morphogenesis can be observed externally in the living embryos, greatly aiding screens for genetic defects. Previous work in ear development has demonstrated that underlying molecular mechanisms are well conserved from human to frog, making genetically amenable and oviparous X. tropicalis an attractive model animal in which to study the causes of hearing and balance anomalies as well as underlying molecular and genetic interactions. Previous screens for inner ear mutants have been done in zebrafish and mouse, and we expect to find both overlapping and different mutations in Xenopus. In this proposal we shall identify and map mutations affecting the ear, and link them to previously known candidate genes, or identify them as new loci involved in ear development. We shall characterize the mutant phenotypes, concentrating on the novel loci. This will establish Xenopus tropicalis as an effective new system to understand ear development and disorders. As described in the Program Announcement, the formation of the human inner ear is complex, and both the normal development and developmental disorders are poorly understood. The understanding of inner ear development will benefit from studies in model organisms such as Xenopus tropicalis, where mutant phenotypes can be used to understand the underlying mechanisms for normal development
Keywords: 0-11 years old; Address; Affect; Alleles; Allelomorphs; Amphibia; Amphibians; Animal Model; Animal Models and Related Studies; Animals; Behavior; Body Tissues; Brachydanio rerio; Candidate Disease Gene; Candidate Gene; Chemicals; Child; Child Youth; Children (0-21); Complex; Danio rerio; Defect; Detection; Development; Disease; Disorder; Ear; Ear structure; Ear, Internal; Embryo; Embryonic; Equilibrium; Event; Exhibits; Fishes; Frog; Gene Expression; Genes; Genes, Regulator; Genetic; Genetic Alteration; Genetic Change; Genetic Models; Genetic Screening; Genetic analyses; Genetic defect; Genetics, in situ Hybridization; Genetics-Mutagenesis; Genome; Hearing; Hearing Loss; Hereditary; Human; Human, Child; Human, General; Hypoacuses; Hypoacusis; In Situ Hybridization; Inherited; Labyrinth; Lead; Lesion; Life; Link; Mammals, Mice; Man (Taxonomy); Man, Modern; Maps; Mice; Modeling; Molecular; Molecular Biology, Mutagenesis; Molecular Genetic; Molecular Genetics; Morphogenesis; Morphology; Murine; Mus; Mutagenesis; Mutation; NIH Program Announcements; Organ; Otic Vesicle; Otoconias; Otoliths; Oviparity; Oviparous; Pattern; Pb element; Phenotype; Phylogeny; Pilot Projects; Prevalence; Process; Program Announcement; Proteins; Rana; Rana (genus); Regulator Genes; Resolution; Role; Sensory; Sound; Sound - physical agent; Statoconia; Statoconias; Structure of otoconia; Swimming; System; System, LOINC Axis 4; Therapeutic; Tissues; Transcriptional Regulatory Elements; Vertebrate Animals; Vertebrates; Work; Xenopus; Zebra Danio; Zebra Fish; Zebrafish; balance; balance function; cell type; children; comparative; developmental disease/disorder; developmental disorder; disability; disease/disorder; equilibration disorder; gene function; gene product; genetic analysis; genome mutation; hearing impairment; hearing perception; heavy metal Pb; heavy metal lead; in situ Hybridization Staining Method; inner ear; insight; model organism; mutant; novel; otoconia; otocyst; otocyst/otolith; pilot study; positional cloning; regulatory gene; reverse genetics; social role; sound; sound perception; trans acting element; vertebrata; youngster
Relevance: As described in the Program Announcement, the formation of the human inner ear is complex, and both the normal development and developmental disorders are poorly understood. The understanding of inner ear development will benefit from studies in model organisms such as Xenopus tropicalis, where mutant phenotypes can be used to understand the underlying mechanisms for normal development
Project start date: 2009-08-10
Project end date: 2011-07-31
Budget start date: 1-AUG-2010
Budget end date: 31-JUL-2011
PFA/PA: PA-06-365
5R21DC010210-02 (2010): $189956
1R21DC010210-01 (2009): $205330
AXIS FORMATION IN VERTEBRATE DEVELOPMENT
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM049346-12 from National Institute Of General Medical Sciences IRG: CDF
Abstract: The long-term goal of our work is to understand vertebrate development at the molecular level. In previous grant periods, we have characterized the activities of BMP antagonists. In the next five years, we will examine the biological roles and mechanisms of antagonists of TGF-beta 3 family members further, with a particular emphasis on their roles in organogenesis. These experiments will rely on gain of function analysis in Xenopus and loss of function analysis in the mouse. The experiments will be complemented by biochemical analysis of the mechanisms by which antagonists block BMP function.
Keywords: bone morphogenetic protein, developmental genetics, gene expression, histogenesis, protein structure function, receptor binding, transforming growth factor, vertebrate embryology, genetic regulation, growth factor receptor, protein binding, receptor expression, Xenopus, high performance liquid chromatography, in situ hybridization, laboratory mouse
Project start date: 1993-05-01
Project end date: 2005-06-30
5R01GM049346-12 (2004): $275764
Sponsored Links Excellgen http://Excellgen.com
5R01GM049346-11 (2003): $275984
5R01GM049346-10 (2002): $276185
3R01GM049346-12S1 (2004): $25000
2R01GM049346-09 (2001): $276367
5R01GM049346-08 (2000): $220984
5R01GM049346-07 (1999): $214908
5R01GM049346-06 (1998): $208722
2R01GM049346-05 (1997): $202067
COMPARATIVE GENETICS OF SKELETAL DEFECTS
Richard M Harland
University Of California Berkeley, 2150 Shattuck Avenue, Room 313, Berkeley, Ca 94704-5940
Grant 5R01HD047853-05 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: The goal of this research is to understand the molecular mechanisms by which congenital skeletal disorders lead to pronounced developmental and radiological bone alterations. In particular the PIs are interested in two progressive hyperosteosis disorders Van Buchem disease (VB) (MIM 239100) and Sclerosteosis (MIM 269500). VB is a severe, autosomal-recessive bone disorder characterized by cranio-facial distortion and generalized bone overgrowth. Sclerosteosis is a skeletal dysplasia highly similar to VB but with more pronounced radiological bone alterations (jaw; long bones; gigantism) and the presence of hand abnormalities (syndactyly). Linkage analysis mapped both diseases to the same locus (17q12-q21), and Sclerosteosis patients were found to carry several coding mutations in the BMP-antagonist gene Sclerostin (Sost). In contrast, VB patients exhibit no Sost coding mutations, however displayed a 52kb noncoding deletion, 35kb downstream of the Sost transcript. Using human transgenes in mice, the PIs have demonstrated that sclerosteosis and VB are allelic, and that the 52kb deletion removes essential Sost transcriptional regulatory elements, altering the human Sost expression pattern. Also, in mice, increased levels of Sost result in severe limb abnormalities (fused and split digits), while the lack of mouse Sost leads to hyperosteosis. These initial observations suggest that Sost plays a critical role during limb development as well as throughout the adult-life controlling bone homeostasis in vertebrates. Since Sost is highly conserved from fishes to humans, the PIs are interested in elucidating the role of this molecule during skeletal development in different vertebrates. Accordingly, this grant focuses on deciphering several fundamental properties of Sost including 1) identification and characterization of Sost-specific regulatory elements, 2) determination of the role of Sost in limb patterning and adult bone homeostasis, and 3) investigation of the role of Sost across different vertebrate lineages
Keywords: 17q12-q21; 21+ years old; Abscission; Adult; Amphibia; Amphibians; Animal Model; Animal Models and Related Studies; Animals; Anterior; Autoregulation; BACs (Chromosomes); Bacterial Artificial Chromosomes; Body Tissues; Bone; Bone Diseases; Bone Formation; Bone and Bones; Bone remodeling; Bones and Bone Tissue; Brachydanio rerio; Candidate Disease Gene; Candidate Gene; Chickens; Chromosome 17; Chromosomes, Human, Pair 17; Code; Coding System; Common Rat Strains; Complex; DNA Molecular Biology; DNA Recombination; DNA recombination (naturally occurring); Danio rerio; Defect; Development; Digit; Digit structure; Disease; Disorder; Elements; Embryo; Embryonic; Engineering; Engineerings; Enhancers; Excision; Exhibits; Extirpation; Extremities; Face; Fishes; Frog; Gallus domesticus; Gallus gallus; Gallus gallus domesticus; Gene Expression; Gene Transcription; Genes; Genes, Regulator; Genetic; Genetic Alteration; Genetic Change; Genetic Recombination; Genetic Transcription; Genetic defect; Genetics, in situ Hybridization; Genomics; Gigantism; Gigantisms; Goals; Grant; Hand; Homeostasis; Human; Human Genome; Human, Adult; Human, General; Hyperostosis Corticalis Generalisata; In Situ Hybridization; In Vitro; Investigation; Jaw; Knock-out; Knockout; Lead; Life; Limb Development; Limb structure; Limbs; Linkage Analysis; Long Bone; Mammals, Mice; Mammals, Rats; Man (Taxonomy); Man, Modern; Maps; Methods and Techniques; Methods, Other; Mice; Molecular; Molecular Biology; Morphology; Murine; Mus; Mutate; Mutation; Non-Trunk; Osteoblasts; Osteogenesis; Overexpression; Patients; Pattern; Pb element; Physiologic; Physiological; Physiological Homeostasis; Play; Process; Property; Property, LOINC Axis 2; Protein Overexpression; RNA Expression; Rana; Rana (genus); Rat; Rattus; Recombination; Recombination, Genetic; Regulator Genes; Regulatory Element; RegulatoryElement; Removal; Research; Role; Series; Skeletal Development; Skeletal system; Staging; Structure of long bone; Surgical Removal; Syndactylia; Syndactyly; System; System, LOINC Axis 4; Techniques; Technology; Testing; Tissues; Transcript; Transcription; Transcription Regulation; Transcription, Genetic; Transcriptional Control; Transcriptional Regulation; Transcriptional Regulatory Elements; Transgenes; Transgenic Mice; Transgenic Organisms; Van Buchem disease; Vertebrate Animals; Vertebrates; Zebra Danio; Zebra Fish; Zebrafish; adult human (21+); bone; bone disorder; bone remodelling; comparative; congenital skeletal disorder; disease/disorder; dosage; facial; family based linkage study; genetic linkage analyses; genetic linkage analysis; genome mutation; heavy metal Pb; heavy metal lead; in situ Hybridization Staining Method; in vivo; interest; linkage analyses; long bone; model organism; mutant; overexpress; regulatory gene; resection; response; skeletal; skeletal dysplasia; social role; trans acting element; transgenic; vertebrata
Project start date: 2004-09-30
Project end date: 2010-07-31
Budget start date: 1-AUG-2008
Budget end date: 31-JUL-2010
PFA/PA: RFA-HD-03-024
5R01HD047853-05 (2008): $0
5R01HD047853-04 (2007): $324278
Sponsored Links Excellgen http://Excellgen.com
5R01HD047853-03 (2006): $333964
5R01HD047853-02 (2005): $342000
1R01HD047853-01 (2004): $342000
A HIGH QUALITY GENOME ASSEMBLY FOR XENOPUS TROPICALIS
Richard M Harland
University Of California Berkeley, 2150 Shattuck Avenue, Room 313, Berkeley, Ca 94704-5940
Grant 5R01GM086321-02 from National Institute Of General Medical Sciences
Abstract: Research on Xenopus has provided numerous new insights into cell and developmental biology. The eggs are readily manipulated by microsurgery and microinjection, and with their large size and abundance, either normal or manipulated eggs provide excellent material for biochemical and cell biological analysis. In order to make Xenopus useful for the modern age of "systems biology" where proteomic and genomic analyses promise a comprehensive understanding of life´s processes, a high quality assembly of the Xenopus genome is needed. A high quality genome structure will provide a comprehensive catalog of gene content and proteome, authoritative data on conservation of chromosome structure with other vertebrates, and will improve regions of mis-assembly, bringing short scaffold regions into a chromosome-scale assembly. This proposal builds on the previous high quality draft genome assembly produced at the Department of Energy´s Joint Genome Institute. While the quality is good in gene-rich regions, the long-range assembly of the genome is not as good as that for other tetrapods. This proposal will bypass the previous difficulties in assembling over the long range, by avoiding cloning-based methods of sequence mapping and long-range assembly. Instead we will use high throughput DNA sequencing and statistically based map assembly to generate a physical and genetic map, incorporating newly identified Single Nucleotide Polymorphisms (SNPs) and previously identified Simple sequence length polymorphisms (SSLPs). We will provide support for genome annotation by Metazome and Xenbase and ensure that the resources are made widely available. Work on model organisms has allowed the discovery of many fundamental properties of animals, and thereby allowed new insights into how human embryos develop and function. Xenopus offers large embryos that develop outside the mother, which has enabled discoveries on cell proliferation and many developmental events. The genome structure and full gene set will permit new genes and functions to be identified, functions that are highly relevant to human development and disease
Keywords: Adopted; Age; Animal Model; Animal Models and Related Studies; Animals; Annotation, Automated; Articulation; Biochemical; Biological; Bypass; Cataloging; Catalogs; Cell Growth in Number; Cell Multiplication; Cell Proliferation; Cells; Cellular Proliferation; Chromosomal Organization; Chromosomal Structure; Chromosome Mapping; Chromosome Organization; Chromosome Structures; Chromosomes; Communities; Complement; Complement Proteins; Cote d`Ivoire; DNA; DNA Sequence; DOE; Data; Data Banks; Data Bases; Databank, Electronic; Databanks; Database, Electronic; Databases; Deoxyribonucleic Acid; Department of Energy; Development; Developmental Cell Biology; Disease; Disorder; ESTs; Embryo; Embryonic; Ensure; Europe; Event; Evolution; Expressed Sequence Tags; Family; Female; Frequencies (time pattern); Frequency; Gene Localization; Gene Mapping; Gene Mapping, Total Human and Non-Human; Genes; Genetics, Gene Mapping; Genome; Genome, Human; Genomics; Haploid; Haploidy; Human; Human Development; Human Genome; Human, General; Hybrids; Institutes; Ivory Coast; Joints; Libraries; Life; Linkage Mapping; Maintenance; Maintenances; Mammalia; Mammals; Mammals, General; Man (Taxonomy); Man, Modern; Maps; Methods; Microinjections; Microsurgery; Mothers; PCR; Physical Chromosome Mapping; Physical Mapping (Genetics); Polymerase Chain Reaction; Polymorphism, Single Base; Process; Property; Property, LOINC Axis 2; Proteome; Proteomics; Radiation Hybrid; Research; Research Resources; Resources; SEQ-AN; SNP; SNPs; SSLP; Sequence Analyses; Sequence Analysis; Shotgun Sequencing; Single Nucleotide Polymorphism; Source; Structure; Systems Biology; Time; Universities; Vertebrate Animals; Vertebrates; Washington; Work; Xenopus; annotation schema; automated annotation; base; clinical data repository; clinical data warehouse; computer annotation; computerized data processing; data processing; data repository; density; disease/disorder; egg; gene function; genetic mapping; improved; insight; model organism; public health relevance; relational database; scaffold; scaffolding; sex; signal processing; simple sequence length polymorphism; vertebrata; xenopus genome
Project start date: 2009-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
PFA/PA: PAR-07-144
5R01GM086321-02 (2010): $383819
A GENOME ASSEMBLY FOR XENOPUS LAEVIS
Richard M Harland
University Of California Berkeley, 2150 Shattuck Avenue, Room 313, Berkeley, Ca 94704-5940
Grant 1R01HD065705-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Research on the amphibian Xenopus has provided numerous new insights into cell and developmental biology. With their large size and abundance, they provide unparalleled material for biochemical and cell biological analysis of complex processes such as the cell cycle and chromosome mechanics. For embryological experiments, the embryos are readily manipulated by microsurgery and by microinjection can be subjected to gain or loss of gene function. In order to make Xenopus more useful for the modern age of "systems biology" where proteomic and genomic analyses promise a comprehensive understanding of life´s processes, we propose here to complement the genome assembly of Xenopus tropicalis with a gene and protein level genome assembly for Xenopus laevis. The allotetraploid Xenopus laevis is in wider use than the smaller, diploid Xenopus tropicalis, because of its history, robustness, and the size and quantity of eggs that can be obtained for embryological and cell biological experiments. We propose to carry out high throughput sequencing of X. laevis, and generate a gene-scale assembly. By selecting regions complementary to the X. tropicalis sequence we will be able to assemble X. laevis genes from relatively inexpensive, short read data. The project provides some computational challenges that will need to be overcome and the approaches developed will be of wide utility in characterizing genomes of other organisms. We will provide support for genome annotation by Xenbase and deposit gene and protein collections in public databases to ensure that the resources are widely available. Xenopus laevis eggs and embryos have been the material of choice for work on vertebrate experimental embryology and biochemical dissection of the cell cycle, providing insights into human biology. We propose to fill a large gap in the essential resources for this work, namely a catalogue of the gene and protein content
Keywords: African; Age; Algorithms; Amphibia; Amphibians; Anti-Sense Oligonucleotides; Antisense Agent; Antisense Oligonucleotides; Articulation; Biochemical; Biochemistry; Biological; Biological Models; Cataloging; Catalogs; Cell Cycle; Cell Division Cycle; Cells; Cellular biology; Chemistry, Biological; Chromosomes; Code; Coding System; Collaborations; Collection; Communities; Complement; Complement Proteins; Complex; Computing Methodologies; DISSEC; DNA Sequence; DOE; Data; Data Banks; Data Bases; Data Set; Databank, Electronic; Databanks; Database, Electronic; Databases; Dataset; Department of Energy; Deposit; Deposition; Development; Developmental Cell Biology; Diploid; Diploidy; Dissection; Egg, Unfertilized; Embryo; Embryo Development; Embryogenesis; Embryology; Embryology / Fetal Growth; Embryonic; Embryonic Development; Ensure; Evolution; Functional RNA; Gene Expression Inhibitor; Gene Expression Profile; Gene Proteins; Genes; Genetic; Genital System, Female, Fluids, Secretions, Ova; Genome; Genomics; History; Human Biology; Institutes; Joints; Libraries; Life; Mammalia; Mammals; Mammals, General; Mechanics; Microinjections; Microsurgery; Model System; Models, Biologic; Non-Coding; Non-Coding RNA; Oligonucleotides, Antisense; Organism; Ova, Fluids, Secretions; Ovum; Peptides; Platanna; Process; Protein Gene Products; Proteome; Proteomics; RNA Splicing; Reading; Reagent; Recording of previous events; Relative; Relative (related person); Repetitive Element; Repetitive Regions; Repetitive Sequence; Research; Research Resources; Resources; Splicing; Systems Biology; Technology; Validation; Work; Xenopus; Xenopus laevis; Xenopus sp.; cell biology; clawed frog; clinical data repository; clinical data warehouse; comparative genomics; computational methodology; computational methods; computer methods; data repository; design; designing; egg; egg/ovum; experiment; experimental research; experimental study; gene expression signature; gene function; genome sequencing; improved; insight; living system; paralog; paralogous gene; public health relevance; relational database; research study; transcriptome; transcriptomics
Relevance: Relevance Xenopus laevis eggs and embryos have been the material of choice for work on vertebrate experimental embryology and biochemical dissection of the cell cycle, providing insights into human biology. We propose to fill a large gap in the essential resources for this work, namely a catalogue of the gene and protein content
Project start date: 2010-08-01
Project end date: 2014-05-31
Budget start date: 1-AUG-2010
Budget end date: 31-MAY-2011
PFA/PA: PAR-09-240
1R01HD065705-01 (2010): $305191
Gene Expression In Amphibian Devlopement
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 2R01GM042341-19A1 from National Institute Of General Medical Sciences IRG: ZRG1
Abstract: Our long-term goal is to understand the signals that pattern the early vertebrate embryo. We study this problem predominantly in the frog Xenopus laevis. This animal produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. Many of the paradigms for early developmental mechanisms in vertebrates have come from work with amphibians, and many of the signaling activities that bring about early developmental decisions in vertebrates have been identified first in amphibians. During previous grant periods, we have identified signals that act in early axis formation, mesoderm patterning and neural induction. In conjunction with the work of many other groups, this has led to a coherent picture of how the embryonic axes are established, and how a cascade of signal transductions leads to the elaborate pattern of the gastrula. Despite the progress that has been made in understanding embryonic signals, there is still only a partial picture of how the detailed pattern of the embryo emerges. The intracellular mediation of signaling is poorly understood, and although the main pathways that signal in development have been identified, the precise roles and modulation of these pathways remains to be determined. The formation of the neural plate with its elaborate patterning in both anterior-posterior and mediolateral axes poses a particular challenge, and this proposal will examine the integration of signaling pathways that induce and pattern the neural plate. Particular focus will be given to Fibroblast Growth Factor signaling in neural patterning, and in neural crest formation. The integration of signals that induce the neural crest will be studied by exploiting and comparing various manipulations that bring about neural crest development.
Keywords: biological signal transduction, developmental genetics, early embryonic stage, fibroblast growth factor, gene expression, histogenesis, neural crest, vertebrate embryology, ectoderm, embryogenic cleavage, homeobox gene, mesoderm, neural plate /tube, Xenopus, genetic manipulation, microinjection, microsurgery, molecular cloning, tissue /cell culture
Project start date: 1988-09-01
Project end date: 2009-01-31
2R01GM042341-19A1 (2005): $357504
AXIS FORMATION IN VERTEBRATE DEVELOPMENT
Richard M Harland
University Of California Berkeley, 2150 Shattuck Avenue, Room 313, Berkeley, Ca 94704-5940
Grant 5R01GM049346-18 from National Institute Of General Medical Sciences
Abstract: Our long-term goal is to understand the signals that pattern the early vertebrate embryo, and particularly the role that BMP antagonists play in this process. During previous grant periods, we have identified a number of BMP antagonists that act in early axis formation, mesoderm patterning and neural induction. They are also essential for organogenesis. In the next grant period we will study how these antagonists act, either singly, or more frequently in overlapping combinations, in genetically modified mice. We will use mutant alleles of Noggin and Gremlin, which were both discovered and characterized by our lab, and in addition, we will use mutants of follistatin and chordin. To facilitate the recovery of mutant animals we will use conditional alleles of these genes in combination with Cre drivers. Our particular focus will be the role of the antagonists in development of the somites, gut and skeleton. A variety of protein antagonists of the Bone Morphogenetic Protein signaling pathway are essential regulators of early development. They affect most organs, but are particularly known for their effects on nervous system, skeleton and stem cell development. They have current uses in stem cell culture, and considerable promise for therapies in clinical disorders such as ectopic bone deposition, all of which justifies a thorough understanding of their role in normal development of the mammalian embryo
Keywords: Abscission; Activin-Binding Protein; Affect; Alleles; Allelomorphs; Animals; Apoptosis; Apoptosis Pathway; Arthritis, Degenerative; Articulation; Autoregulation; Body Tissues; Bone; Bone Morphogenetic Proteins; Bone and Bones; Bones and Bone Tissue; Branchial Arches; Branchial arch structure; Cartilage; Cartilagenous Tissue; Cell Communication and Signaling; Cell Culture Techniques; Cell Death, Programmed; Cell Signaling; Clinical; Complication; Defect; Degenerative polyarthritis; Deposit; Deposition; Development; Disease; Disorder; Dorsal; Embryo; Embryonic; Excision; Extirpation; FLR; Failure (biologic function); Follistatin; Genes; Genetic Alteration; Genetic Change; Genetic defect; Goals; Grant; Gut Epithelium; Head; Homeostasis; ICC (Interstitial cell of Cajal); Interstitial Cell of Cajal; Interstitial cell of Cajal (ICC); Intracellular Communication and Signaling; Joints; Location; Longitudinal Studies; Mammals, Mice; Mesoderm; Mice; Mother Cells; Murine; Mus; Mutation; NRVS-SYS; Nervous System; Nervous system structure; Neurologic Body System; Neurologic Organ System; Organ; Organogenesis; Osteoarthritis; Osteoarthrosis; Pattern; Peristalsis; Pharangeal Arch; Pharyngeal Arches; Phenotype; Physiological Homeostasis; Play; Process; Progenitor Cells; Proteins; Recovery; Regulation; Removal; Role; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Skeletal Development; Skeleton; Somites; Stem Cell Development; Stem cells; Structure; Surgical Removal; Tissues; Transducers; Vertebrate Animals; Vertebrates; Villus; Visceral Arches; base; biological signal transduction; bone; branchial arch; cartilage development; cell type; chordin; degenerative joint disease; disease/disorder; failure; fetal; gastrointestinal epithelium; gene product; genome mutation; hypertrophic arthritis; long-term study; mouse development; mutant; neural patterning; nodal myocyte; null mutation; pharyngeal arch; resection; social role; vertebrata
Relevance: A variety of protein antagonists of the Bone Morphogenetic Protein signaling pathway are essential regulators of early development. They affect most organs, but are particularly known for their effects on nervous system, skeleton and stem cell development. They have current uses in stem cell culture, and considerable promise for therapies in clinical disorders such as ectopic bone deposition, all of which justifies a thorough understanding of their role in normal development of the mammalian embryo
Project start date: 1993-05-01
Project end date: 2013-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-07-070
5R01GM049346-18 (2010): $311528
2R01GM049346-17A1 (2009): $314675
GENE EXPRESSION IN AMPHIBIAN DEVELOPMENT
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 3R01GM042341-18S1 from National Institute Of General Medical Sciences IRG: CDF
Abstract: Our long term goal is to understand the signals that pattern the early vertebrate embryo. We study this problem predominantly in the frog Xenopus laevis. This animal produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. Despite the progress that has been made in understanding embryonic signals, there is still only a partial picture of how the detailed pattern of the embryo emerges. The main hypothesis driving work in the next grant period is that there are a substantial number of embryonic signaling activities that remain to be identified. We will identify these signals so that they can be further understood at the embryological and molecular level. In the next grant period, there are three general areas that will be pursued We will study signals from the neural plate that influence mesodermal and neural fates. We will further dissect the wnt signal transduction pathway that leads to early events of axis formation, and sensitization of the ectoderm to neuralizing signals. Finally, we will use our proven expression cloning techniques to isolate and study molecules that influence mesodermal and neural pattern. Many of the same cellular mechanisms are used in embryos and in adults; therefore an increased understanding of the basic biology of development will improve our understanding of human development and physiology.
Keywords: biological signal transduction, developmental genetics, early embryonic stage, gene expression, histogenesis, vertebrate embryology, ectoderm, embryogenic cleavage, homeobox gene, mesoderm, neural plate /tube, Xenopus, genetic manipulation, laboratory mouse, laboratory rabbit, microinjection, microsurgery, molecular cloning, tissue /cell culture
Project start date: 1988-09-01
Project end date: 2005-01-31
3R01GM042341-18S1 (2004): $117484
Sponsored Links Excellgen http://Excellgen.com
2R01GM042341-15 (2000): $336473
Axis Formation In Vertebrate Development
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM049346-15 from National Institute Of General Medical Sciences IRG: DEV
Abstract: Our long term goal is to understand the signals that pattern the early vertebrate embryo, and particularly the role that BMP antagonists play in this process. We study this problem in both amphibians and mice, since each offers different experimental advantages. Xenopus laevis produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. We also complement use of X. laevis with use of X. tropicalis, which offers the advantages of diploidy and a sequenced genome, both advantages for manipulating gene expression by Morpholino oligonucleotide-mediated knockdowns. Our work in the mouse has taken advantage of targeted mutations. The phenotypes of these mutations have suggested particular developmental contexts where BMP antagonists are crucial, and some of these contexts are particularly relevant to human developmental disorders. In the next grant period we will study how BMP antagonists implement important developmental decisions, either singly, or in overlapping combinations. These include the maintenance of neural stem cell populations and skeletal patterning in noggin mutants, and the induction and maintenance of somite differentiation in noggin/gremlin double mutants. Finally we will study the contribution of different BMP antagonists to formation of the dorsal ventral, and anterior posterior axes in the early embryo.
Keywords: bone development, bone morphogenetic protein, developmental genetics, gene expression, growth factor receptor, histogenesis, neurogenetics, vertebrate embryology, antibody, brain cell, craniosynostosis, gene interaction, gene mutation, genetic regulation, head, mesoderm, molecular biology, neural crest, skull, spinal cord, Xenopus, genetically modified animal, laboratory mouse, laboratory rabbit
Project start date: 1993-05-01
Project end date: 2009-06-30
5R01GM049346-15 (2007): $280417
5R01GM049346-14 (2006): $289525
2R01GM049346-13 (2005): $297176
Gene Expression In Amphibian Development
Richard M Harland, Professor
Molecular And Cell Biology (mcb)university Of California Berkeley
Grant 2R01GM042341-23 from National Institute Of General Medical Sciences IRG: DEV1
Abstract: Our long term goal is to understand early vertebrate development at the molecular level. We study the problem in the frog Xenopus, which produces large numbers of eggs that are readily manipulated by microinjection and microsurgery. A combination of experimental embryology and molecular xmanipulation provides methods to understand the roles of specific genes and signaling pathways in elaborating the structure of the embryo. Most of the paradigms for development of vertebrate embryos have come first from work with amphibians, and many of the signaling activities were first analyzed using amphibian embryos. Gain of function experiments using mRNA injection, and loss of function using Morpholino oligonucleotides have provided insights into the mechanisms that underlie tissue differentiation and morphogenesis. During previous grant periods, we have used expression cloning to identify potent signaling and signal transduction activities that contribute to embryonic development. In screens for embryonic activities that alter neural patterning we identified several RNA regulators that show specific effects in both gain of function and loss of function experiments. In the next grant period, we will analyze selected RNA binding and pre-mRNA splice regulating activities that show such highly specific effects on development, and will therefore gain new insight into the selective effect of these proteins on specific splicing choices. The control of alternative pre- mRNA splicing has emerged as an important mechanism in gene control, and recent methods allow a global analysis of changes in splicing that are directed by specific proteins. We will apply these methods in Xenopus to understand how these proteins regulate splice choices, and thereby resolve the previously unknown function of these splicing regulators in splicing choices. Mapping of mutations that cause human diseases showed that many mutations are found in the conserved splicing junctions or branchpoint sequences of precursors to protein coding messenger RNAs, rather than in the protein coding sequence of the mRNA. It is therefore crucially important to understand the mechanisms that regulate the use of splicing signals, in order to understand the susceptibility to and etiology of diseases, as well as to devise therapies for such disease. This proposal will advance our understanding of splicing regulation using the model vertebrate organism, Xenopus, which affords technical advantages in manipulating splicing regulators, and studying the consequences of this manipulation
Project start date: 1988-09-01
Project end date: 2013-01-31
CONCEPTS AND MODEL ORGANISMS IN REGENERATIVE BIOLOGY
Richard M Harland
Society For Developmental Biology, Bethesda, Md 20814-3998
Grant 1R13HD066961-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Funds are requested for partial support of U.S.-based scientists and students in the Americas to participate in the Short Course Concepts and Model Organisms in Regenerative Biology, to be held at Pontificia Universidad Cat¿lica de Chile in Santiago, Chile, November 2-11, 2010. This will be the third major collaborative training event between the Society for Developmental Biology (SDB) and the Latin American Society for Developmental Biology (LASDB) in Latin America, with the participation of distinguished scientists and top students from the United States (15) and Latin American countries (15). The first two short courses were held in spring of 2005 in Brazil and fall of 2008 in Argentina. This third course will be satellite to the LASDB´s 5TH International Meeting, which will allow the students to attend and present their own work to a larger international audience. Regenerative biology is not usually covered in developmental biology courses, despite the obvious correlation between these two processes. This course will emphasize the common steps and advances that have allowed us to further understand how organisms develop and maintain their integrity in adulthood, and the potential applications in medicine in the near future. Students will be exposed to the fundamental concepts, questions, model organisms, and research tools used in both areas, and will be encouraged to draw their own associations between these processes. The instructors were selected primarily for the excellence of their research in respective specialties, their dynamic teaching approach, and their willingness to continue collaborative efforts after the course. They will give a balanced view of the potentials and limitations of the traditional and emerging technologies, as well as model organisms used in such studies. The practical sessions held in laboratories with state-of-the-art equipment will provide plenty opportunity for the students to acquire hands-on experience working with different organisms that have well-known as well as those with uncommon regenerative properties mouse, frog, zebrafish, salamander, fly, roundworm, planarian, sea cucumber, and plant. Students will be selected from applications submitted by postdoctoral fellows and advanced graduate students in the U.S., and from graduate students, postdoctoral fellows, and young faculty in Latin America, based on their previous experience and interest in the field. Latin American faculty in other disciplines who are considering a change in the focus of their research to regenerative/developmental biology will also be eligible. Most of the students in the short course are expected to enter the pipeline for supply of future investigators and educators in biology and related areas. This short course will broaden the exposure of these students to the fields of regenerative and developmental biology, in the form of a training event of the highest quality, as well as to offer opportunities to work with established laboratories in the various countries. This short course "Concepts and Model Organisms in Regenerative Biology" is organized jointly by the Society for Developmental Biology (in U.S.) and the Latin American Society for Developmental Biology (LASDB). It aims in training postdoctoral fellows and advanced graduate students in the Western Hemisphere in understanding the fundamental questions and innovative approaches in developmental and regenerative biology, and in its applications to health. The selected students are in the pipeline for supplying future investigators and faculty in this and related areas, and will enhance collaborative research efforts among the laboratories in the Americas
Keywords: 21+ years old; Address; Adult; American; Americas; Animal Model; Animal Models and Related Studies; Area; Argentina; Arts; Biology; Brachydanio rerio; Brazil; Chile; Collaborations; Country; Country of Argentina; Danio rerio; Development; Developmental Biology; Discipline; Educational process of instructing; Emergent Technologies; Emerging Technologies; Equilibrium; Equipment; European; Event; Faculty; Flies; Fostering; Frog; Funding Applicant; Future; Hand; Health; Holothuroidea; Human, Adult; International; Investigators; Laboratories; Latin America; Mammals, Mice; Medical Specialities; Medicine; Mice; Murine; Mus; Nematoda; Nematodes; Organism; Planarians; Plants; Plants, General; Postdoc; Postdoctoral Fellow; Process; Property; Property, LOINC Axis 2; Rana; Rana (genus); Research; Research Associate; Research Personnel; Researchers; Salamander; Science of Medicine; Scientist; Sea Cucumbers; Societies; Specialties, Medical; Specialty; Students; Teaching; Therapeutic Uses; Training; United States; Work; Zebra Danio; Zebra Fish; Zebrafish; adult human (21+); balance; balance function; base; experience; falls; fly; forging; graduate student; innovate; innovation; innovative; instructor; interest; living system; medical specialties; meetings; model organism; post-doc; post-doctoral; regenerative; roundworm; tool; willingness
Relevance: Harland, Richard M. Concepts and Model Organisms in Regenerative Biology This short course Concepts and Model Organisms in Regenerative Biology is organized jointly by the Society for Developmental Biology (in U.S.A.) and the Latin American Society for Developmental Biology (LASDB). It aims in training postdoctoral fellows and advanced graduate students in the Western Hemisphere in understanding the fundamental questions and innovative approaches in developmental and regenerative biology, and in its applications to health. The selected students are in the pipeline for supplying future investigators and faculty in this and related areas, and will enhance collaborative research efforts among the laboratories in the Americas
Project start date: 2010-09-01
Project end date: 2011-08-31
Budget start date: 1-SEP-2010
Budget end date: 31-AUG-2011
PFA/PA: PA-08-149
1R13HD066961-01 (2010): $16000
TRAINING GRANT IN DEVELOPMENTAL BIOLOGY
Richard M Harland, Professor And Chair
Molecular And Cell Biology (mcb)university Of California Berkeley
2150 Shattuck Avenue, Room 313
berkeley, Ca 947045940
Grant 5T32HD007375-15 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development IRG: ZHD1
Project start date: 1988-09-30
Project end date: 2003-04-30
5T32HD007375-15 (2002): $206552
5T32HD007375-14 (2001): $194859
5T32HD007375-13 (2000): $157260
5T32HD007375-12 (1999): $180854
Sponsored Links Excellgen http://Excellgen.com
2T32HD007375-11 (1998): $148691
5T32HD007375-10 (1997): $136267
AXIS FORMATION IN VERTEBRATE DEVELOPMENT
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5R01GM049346-04 from National Institute Of General Medical Sciences IRG: CBY
Project start date: 1993-05-01
Project end date: 1997-04-30
5R01GM049346-04 (1996): $187975
TRAINING GRANT IN DEVELOPMENTAL BIOLOGY
Richard M Harland, Professor And Chair
University Of California Berkeley 2150 Shattuck Avenue, Room 313 Berkeley, Ca 947045940
Grant 5T32HD007375-09 from National Institute Of Child Health And Human Development IRG: HDMC
Project start date: 1988-09-30
Project end date: 1998-06-30
5T32HD007375-09 (1996): $133548