Research focuses on controls regulating developmental gene expression and tissue morphogenesis. The cellular slime mold, Dictyostelium discoideum, one of the simplest organisms to undergo true multicellular differentiation is used as a model system. Several projects are in progress. The projects all utilize a combination of Molecular Genetics, Cell Biology and Biochemistry to determine the function of developmentally important genes which play a role in tissue morphogenesis or to dissect controls regulating cell type specific gene expression. The three main projects are briefly described below.
1) One gene being studied encodes a protein that functions as a novel anti-adhesive, facilitating cell migration. The gene also regulates cell type proportioning. Current work focuses on determining the mechanism of action of the gene in regulating the proportion of different cell types and in modulating cell-cell and cell-substrate adhesion. A variety of approaches are being used to identify proteins that interact with the anti-adhesive protein and to knock out genes encoding the interacting proteins to determine their role in developmental morphogenesis.
2) Another gene under study is expressed only in the prespore cells. Analysis of the promoter reveals a novel form of negative regulation. An element within the coding region of the gene is responsible for preventing expression of the gene in prestalk cells. Work is directed at determining if the negative element acts as a site for transcriptional repression or directs degradation of the mRNA in prestalk cells.
3) A third family of genes being studied encode ribosomal proteins. At the onset of development translation of these mRNAs shuts off in cells destine to become prespore cells but continues in cells that will become prestalk cells. The prestalk cells undergo a form of programmed cell death and a key question of interest is whether the continued expression of the ribosomal protein genes under the starvation conditions of development is responsible for activating the death pathway in these cells. The 5' non-translated leader sequence on the mRNA is responsible for the cell type specific regulation of the ribosomal protein genes and other work in the lab seeks to identify factors that interact with the mRNA sequences in effecting this regulation and to identify genes which function in the pathway that leads to shut off of these gene in prespore cells.
Blumberg, D.D. , Ho, H., Petty, C., Varney, T and Gandham, S.. (2002) AmpA, a modular protein containing disintegrin and ornatin domains, has multiple effects on cell adhesion and cell fate specification. J. Muscle Res. Cel. Motil. 23:817-28. (Abstract).
Varney, T.R., Ho, H., Petty, C. and D.D. Blumberg (2002) A novel disintegrin domain protein affects early cell type specification and pattern formation in Dictyostelium. Development: 129: 2381-2389. (Abstract)
Varney, T. R., Casademunt, E., Ho, H., Petty, C., Dolman, J., and Blumberg, D. D. (2002). A novel Dictyostelium gene encoding multiple repeats of adhesion inhibitor-like domains has effects on cell-cell and cell-substratum adhesion. Developmental Biology 243: 226-248. Abstract
Casademunt, E., Varney, T. R., Dolman, J., Petty, C., and Blumberg, D. D. (2002). A gene encoding a novel anti-adhesive protein is expressed in growing cells and restricted to anterior-like cells during development of Dictyostelium. Differentiation. 70:23-35. Abstract
Agarwal, A.K., S.N. Parrish and D.D. Blumberg (1999) Ribosomal protein gene expression is cell type specific during development in Dictyostelium discoideum. Differentiation. 65:73-88. Abstract
Agarwal, A.K., and D.D. Blumberg (1999) Dictyostelium Ribosomal Protein genes and the Elongation Factor 1B gene show coordinate developmental regulation which is largely under post-transcriptional control. Differentiation. 64:247-254. Abstract
Varney, T., E. Casademunt, C. Petty, B. Kondo, J. Dolman and D.D. Blumberg. (1999) A protein containing disintegrin and ornatin like
domains modulates cell adhesion in Dictyostelium. Develop. Biol. 210: 243. Abstract
Blumberg, D.D., T. Varney, S. Parrish, E. Casademunt and J. Dolman. (1997) A protein containing disintegrin and ornatin like domains modulates cell adhesion and cell type proportioning in Dictyostelium. Mol. Biol. Cell. supplement V8:32. Abstract
Yoder, B.K., and D.D. Blumberg. 1994. The promoter of a gene encoding a novel Dictyostelium spore coat protein. Develop. Biol. 163 :38-48. Abstract
Yoder, B.K., J. Mao, G.W. Erdos, C.M. West, and D.D. Blumberg. 1994. Identification of a new spore coat protein gene in the cellular slime mold, Dictyostelium discoideum. Develop. Biol. 163 :49-65. Abstract
Agarwal, A.K., M.S. Sloger, M. Oyama, and D.D. Blumberg. 1994. Analysis of a novel cAMP inducible prespore gene in Dictyostelium discoideum: Evidence for different patterns of cAMP regulation. Differentiation 57: 151-62. Abstract