Difference: MaryBaylies (3 vs. 4)
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| > > | Public information on Grants associated with NYSBC Grant Number: 5R01GM056989-09 Project Title: Cell Fate Determination in the Mesoderm of Drosophila PI Information: Name Email Title BAYLIES, MARY K. m-baylies@ski.mskcc.org ASSOCIATE MEMBER | |||||||||||||||||||||||||||||||||||||||||||||||
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| > > | Abstract: DESCRIPTION (provided by applicant): The need for better therapies to treat muscle wasting is growing, a need driven by diseases such as muscular dystrophy, by chemotherapies and by the rapidly aging populations of the developed world. Successful new therapies will generate myoblasts that fuse the appropriate number of times and reshape the targeted muscles. A barrier to developing those therapies, however, is the missing critical information about how myoblasts translate their identity information into a muscle's size, shape, orientation and association with surrounding cells, i.e., characteristics collectively called a muscle's morphology. The goal of this proposal is to connect the genes that control identity to the processes that elaborate the muscle morphology. This will result in an understanding the genes and processes critical to acquisition of size and shape during both development and disease. Drosophila muscle morphogenesis is a highly effective model system to use in this investigation, due to the unique genetic, cellular, and genomic approaches that it affords. Based on published and preliminary data, we propose that the combined activities of 5 transcriptional regulators, Kruppel, Twist, Apterous, Caupolican, and Muscle Segment Homeobox, control the morphogenesis of the lateral muscles. We will categorize the muscle attributes (size, shape, orientation or attachment) that are affected by each regulator. We will determine which of these factors regulate each other and which collaborate to regulate distinct aspects of muscle morphogenesis. We then will determine which aspects of FC cellular behavior are controlled by these regulators during morphogenesis. Lastly, we will begin to identify target genes regulated by these FC identity regulators. Taken together, a picture will emerge of the processes and the genes that regulate specific morphological characteristics. Our work will have direct application to vertebrate muscle morphogenesis and therapies, and to the mechanisms underlying several human diseases. For example, two cranial-facial disorders, Saethre-Chotzen syndrome and Wolf-Hirschhom Syndrome, have been linked to human TWIST and MSXl(Msh), respectively. Additionally, human Twist has been found to play a central role in tumor metastasis. Our work in Drosophila on the mechanisms and targets of these regulators' action will provide insight as to the underlying causes of these diseases and will help to reveal potential therapies. | |||||||||||||||||||||||||||||||||||||||||||||||
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| > > | Public Health Relevance:
This Public Health Relevance is not available.
Thesaurus Terms:
cell morphology, genetic regulation, histogenesis, homeobox gene, mesoderm, muscle, protein protein interaction, transcription factor
DNA binding protein, cell differentiation, cell population study, cell type, gene dosage, gene expression, gene interaction, gene mutation, myogenesis
Drosophilidae, confocal scanning microscopy
Institution: SLOAN-KETTERING INSTITUTE FOR CANCER RES 1275 YORK AVE NEW YORK, NY 10065 Fiscal Year: 2008 Department:
Project Start: 01-JAN-1999 Project End: 31-MAR-2010 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: SMEP
Grant Number: 5R01GM078318-02 Project Title: Mechanisms Regulating Myoblast Fusion in Drosophila PI Information: Name Email Title BAYLIES, MARY K. m-baylies@ski.mskcc.org ASSOCIATE MEMBER Abstract: DESCRIPTION (provided by applicant): Muscles in both humans and Drosophila are composed of multinucleate myofibers that are generated by the fusion of myoblasts. However, the events and molecules that regulate myoblast fusion are not well understood. Our long-term goal is to understand myoblast fusion, and in particular, the regulation of the number of fusion events required to create a muscle fiber. The objective of this proposal is to determine the critical cellular and molecular mechanisms controlling myoblast fusion in the model organism, Drosophila melanogaster. The conservation of genes and mechanisms in muscle development between Drosophila and mammals allows us to use the simpler Drosophila system to make relevant discoveries for treatments of human muscular diseases and of muscle wasting due to aging and chemotherapies. Our central hypothesis in this proposal is that specific cytoskeletal rearrangements are critical for myoblast fusion. Guided by our strong preliminary data, this hypothesis will be tested in three specific aims: (1) Identify the critical cytoskeletal rearrangements that underlie myoblast fusion; (2) Determine the requirement of known fusion genes in regulating specific cytoskeletal behaviors underlying myoblast fusion; and (3) Identify the role of new fusion genes in regulating the specific cytoskeletal rearrangements critical for myoblast fusion. Under the first aim, we have developed novel imaging techniques to identify cytoskeletal rearrangements during myoblast fusion in living and fixed embryos. Our preliminary data has pinpointed several such important cytoskeletal rearrangements. Under the second aim, we will test the impact of known fusion genes in relationship to these cytoskeletal rearrangements. Already we can link specific genes' activities to specific cytoskeletal rearrangements. Under the third aim we will investigate the mechanisms underlying the cytoskeletal changes during fusion by examining novel genes that we have identified. Our work is significant because it expected to reveal the cellular and molecular mechanisms underlying cell-cell fusion. The proposed research is relevant to public health because once the molecular players and the cellular targets of their action are identified or understood, therapies designed to regulate myoblast fusion can be developed to promote fusion for the treatment of muscle wasting due to aging or disease. Public Health Relevance: This Public Health Relevance is not available. Thesaurus Terms: Drosophilidae, myoblast Diptera, actin, adhesion, aging, atrophy, base, behavior, cell, cell biology, cell fusion, cell migration, chemotherapy, choice, cytoskeleton, embryogenesis, emotion, fertilization, flying, fusion gene, gene, gene mutation, human, identity, membrane, metastasis, model, molecular genetics, motivation, muscle, muscle protein, muscular dystrophy, mutant, neoplasm /cancer, organism, orientation, physiologic bone resorption, physiology, play, protein, public health, role, seed, stem cell, success, therapy Institution: SLOAN-KETTERING INSTITUTE FOR CANCER RES 1275 YORK AVE NEW YORK, NY 10065 Fiscal Year: 2008 Department: Project Start: 01-AUG-2007 Project End: 31-JUL-2011 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: SMEP | |||||||||||||||||||||||||||||||||||||||||||||||
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