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Cellular Signaling and Regulation. Membranes and Membrane Proteins. Molecular and Structural Biophysics. Protein-Protein Interactions. Post-translational Modifications. RNA Processing. Single-molecule imaging. Pavletich, Nikola P. BCMB Home.
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Ghabrial earned his Ph. Ghabrial did his postdoctoral work with Dr. His postdoctoral work focused on the design and completion of a saturation-scale screen for tube morphogenesis genes required during the development of the tracheal respiratory system. Ghabrial started his own group at the University of Pennsylvania in The human ortholog of CCM3 Cerebral Cavernous Malformations 3 is one of three genes known to be affected in cases of familial cerebral cavernous malformations.
Cerebral angiomas are found in as many as 1 in every individuals, and is currently treated by brain surgery. Most organs are composed of interconnected networks of tubes of differing sizes, shapes and cellular architectures; my laboratory aims to understand the genetic, cell biological and molecular mechanisms by which these tubes are generated, shaped, and maintained. We use the Drosophila tracheal system as a model, and have initiated a systematic analysis rooted in a classical forward genetic approach, with follow-up studies utilizing cutting edge cell biological and molecular genetic approaches.
Tip cell selection. During primary branching of the tracheal system, much like during sprouting angiogenesis, tip cells initiate the outgrowth of new tubes. Thus, the initial step in the budding of new branches is the selection of a few tip cells from an epithelium in which most if not all cells are competent to behave as tip cells. In the fly tracheal system, Breathless-FGFR and Notch are key receptors that promote or inhibit tip cell selection, respectively 1.
We seek to uncover other factors that regulate tip cell selection, and also to identify the genes required to carry out tip cell behaviors. We have identified mutations that result in the selection of excess tip cells in homozygous mutant embryos, and other mutations for which homozygous cells within mosaic animals are disproportionately present at branch tips. We are also carrying out pilot screens to identify genes required for cells to behave as tip cells. In addition, we are developing an optogenetic system to allow activation of the FGFR pathway with precise spatial and temporal resolution, permitting perturbation of tip cell competition in vivo in real time.
The preliminary data from these studies will form the basis of a new R01 proposal. Morphogenesis of seamless tubes. Seamless tubes are found throughout the animal kingdom, with the best-characterized examples including the terminal cell tubes of the Drosophila tracheal system and the seamless endothelial cell tubes of the vertebrate vascular system. We have published 4 major studies describing the regulation of the apical membrane domain and apical proteins in growing seamless tubes One study revealed a novel mechanism for guiding growth of seamless tubes along the proximal-distal axis, and established a requirement for minus-end directed trafficking along microtubules for tube growth 3.
A second study identified an essential role of endocytosis in regulating the levels of apical proteins Crumbs, Phospho-Moesin , which in turn regulate stiffness of the apical actin cytoskeleton, thereby constraining tube shape and growth 4. We have also broken new ground on the question of how seamed and seamless tubes connect within terminal cells, and published the characterization of the first set of mutations in which seamed and seamless tubes fail to connect, fail to maintain that connection, or become grossly dilated at the site of connection.
Wounding of the terminal cell was also able to elicit the compensatory branching program in the neighboring stalk cell. Science 42 , — doi Uniqueness, diversity, similarity, repeatability, and heritability. International Journal of Comparative Psychology 17 , — Paweletz, N. Walther Flemming: Pioneer of mitosis research. Nature Reviews Molecular Cell Biology 2 , 72—75 doi Chromosome Theory and the Castle and Morgan Debate. Discovery and Types of Genetic Linkage. Genetics and Statistical Analysis. Thomas Hunt Morgan and Sex Linkage. Developing the Chromosome Theory.
Genetic Recombination. Gregor Mendel and the Principles of Inheritance. Mitosis, Meiosis, and Inheritance. Multifactorial Inheritance and Genetic Disease. Non-nuclear Genes and Their Inheritance. Polygenic Inheritance and Gene Mapping. Sex Chromosomes and Sex Determination. Sex Determination in Honeybees.
Mitosis vs. Meiosis: Key Differences, Chart and Venn Diagram | Technology Networks
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Genetic Dominance: Genotype-Phenotype Relationships. Phenotype Variability: Penetrance and Expressivity. Although mitosis and meiosis both involve cell division, they transmit genetic material in very different ways. What happens when either of these processes goes awry? Aa Aa Aa.
Gene Transmission in Mitosis. Figure 1. Gene Transmission in Meiosis. Pairing of homologous chromatids results in hundreds to thousands of individual chromatid copies aligned tightly in parallel to produce giant, "polytene" chromosomes. High-pressure treatment of polytene chromosomes improves structural resolution. Nature Methods 4, All rights reserved. Aberrations That Alter Chromosome Number.
Nondisjunction, in which chromosomes fail to separate equally, can occur in meiosis I first row , meiosis II second row , and mitosis third row.
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These unequal separations can produce daughter cells with unexpected chromosome numbers, called aneuploids. When a haploid gamete does not receive a chromosome during meiosis as a result of nondisjunction, it combines with another gamete to form a monosomic zygote. When a gamete receives a complete homologous chromosome pair as a result of nondisjunction, it combines with another gamete to form a trisomic zygote.
Genetics: A Conceptual Approach , 2nd ed. Trisomy in any of Jimsonweed's 12 chromosomes will cause seed pods to deviate from a wild-type, spherical shape.
References and Recommended Reading Belling, J. Genetics: A Conceptual Approach W. Freeman, New York, Article History Close. Keywords Keywords for this Article. Flag Inappropriate The Content is: Objectionable. Email your Friend. This content is currently under construction.