Theoretical and experimental studies on a cell number counting mechanism

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dc.contributor.advisorGomer, Richard H.en_US
dc.creatorJang, Wonheeen_US
dc.date.accessioned2009-06-04T06:47:07Zen_US
dc.date.available2009-06-04T06:47:07Zen_US
dc.date.issued2004en_US
dc.description.abstractIt is unclear how organisms regulate the size of their components during development. Dictyostelium discoideum form evenly sized groups of ∼2 x 104 cells during aggregation. One mechanism that Dictyostelium use to control group size is by breaking up the aggregation stream when too many cells are present. We developed a computer model in which the cells are treated as discrete points having random motility and adhesion. The model predicted that stream breakup can be regulated by modulating adhesion and motility. The model also showed that a precise group size control can be achieved by having the local concentration of a secreted factor modulating adhesion and motility. In Dictyostelium , a secreted 450 kDa protein complex called counting factor (CF) regulates group size by repressing cell-cell adhesion and increasing cell motility. To identify components involved in the CF signal transduction pathway, we performed random mutagenesis to find possible second-site enhancers or suppressors of a transformant lacking bioactive CF. The analysis of one enhancer (icdh-) suggested that icdh - cells may have a defect in the CF signal transduction pathway. In icdh- cells, one of the isocitrate dehydrogenase genes is disrupted, which will lead to the accumulation of citrate. Since citrate downregulates glycolysis, the internal glucose levels may be altered. Therefore, we examined the possibility that CF decreases group size by regulating internal glucose levels. We found that glucose is a downstream component of the CF signaling pathway, and that CF decreases group size in part by repressing internal glucose levels. CF also repressed the levels of glycogen, pyruvate, lactate, ATP, and oxygen consumption. The ability of CF to decrease internal glucose levels was not linked to the synthesis or degradation of glycogen, but to the repression of gluconeogenesis by decreasing the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase. Our working hypothesis is that CF decreases group size by downregulatmg the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase, resulting in the changes in the signaling cascade, which will in turn regulate adhesion and motility to induce stream to break up in Dictyostelium .en_US
dc.format.extent196 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS BIOCHEM. 2004 JANGen_US
dc.identifier.citationJang, Wonhee. "Theoretical and experimental studies on a cell number counting mechanism." (2004) Diss., Rice University. <a href="https://hdl.handle.net/1911/18649">https://hdl.handle.net/1911/18649</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/18649en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectMolecular biologyen_US
dc.subjectCell biologyen_US
dc.titleTheoretical and experimental studies on a cell number counting mechanismen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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