Gregory J. Podgorski

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Genetic regulatory networks (GRNs) control gene expression and are responsible for establishing the regular cellular patterns that constitute an organism. This paper introduces a model of biological development that generates cellular patterns via chemical interactions. GRNs for protein expression are generated and evaluated for their effectiveness in(More)
The development and cellular differentiation of Dictyostelium discoideum are disrupted in transformants secreting high levels of the cyclic nucleotide phosphodiesterase. The aggregation of these cells in the early stage of development proceeds rapidly and without the formation of organized streams. The later stages of development, in which differentiation(More)
The secreted cyclic nucleotide phosphodiesterase (PDE) and its glycoprotein inhibitor (PDI) are among the first genes expressed when Dictyostelium amoebae begin their development. We used a series of mutants with defects in signal transduction to ask whether cAMP receptors 1 and 3, G alpha2, G beta, adenylyl cyclase (ACA), or the protein kinase A catalytic(More)
The cyclic nucleotide phosphodiesterase of Dictyostelium discoideum functions to maintain the responsiveness of cells to the chemoattractant cAMP during the aggregation phase of development. We have prepared a cDNA library and have isolated clones which contain a portion of the 5' untranslated region and the entire coding and 3' untranslated portions of the(More)
Cellular differentiation during development is controlled by gene regulatory networks (GRNs). This complex process is always subject to gene expression noise. There is evidence suggesting that commonly seen patterns in GRNs, referred to as biological multistable switches, play an important role in creating the structure of lineage trees by providing(More)
The cyclic nucleotide phosphodiesterase (phosphodiesterase) of Dictyostelium discoideum plays an essential role in development by hydrolyzing the cAMP used as a chemoattractant by aggregating cells. We have studied the biochemistry of the phosphodiesterase and a functionally related protein, the phosphodiesterase inhibitor protein, and have cloned the(More)
Solid tumors must recruit new blood vessels for growth and maintenance. Discovering drugs that block this tumor-induced development of new blood vessels (angiogenesis) is an important approach in cancer treatment. However, the complexity of angiogenesis and the difficulty in implementing and evaluating rationally-designed treatments prevent the discovery of(More)
Solid tumors must recruit new blood vessels for growth and maintenance. Discovering drugs that block tumor-induced development of new blood vessels (angiogenesis) is an important approach in cancer treatment. The complexity of angiogenesis presents both challenges and opportunities for cancer therapies. Intuitive approaches, such as blocking VegF activity,(More)
The cyclic nucleotide phosphodiesterase (phosphodiesterase) gene plays essential roles in the development of Dictyostelium discoideum during cellular aggregation and postaggregation morphogenesis. Genomic clones spanning the gene were isolated and used to determine the sequence and structure of the phosphodiesterase gene. We found an unusually complex(More)
We used a computational approach to examine three questions at the intersection of developmental biology and evolution: 1) What is the space available for evolutionary exploration for genetic regulatory networks (GRNs) able to solve developmental patterning problems? 2) If different GRNs exist that can solve a particular pattern, are there differences(More)