Cell Signaling and Differentiation
The mission of the Cell Signaling and Differentiation node is to gain a deeper understanding of development and disease through genome- and proteome-wide analyses. One broad goal is to generate more complete catalogs of gene expression profiles and to decipher gene regulatory networks in particular tissues and cell types. Another broad goal is to investigate how misregulation of basic processes, such as DNA repair, chromatin organization, and cell proliferation, contributes to the genesis and progression of cancer. The latter studies will strenghten basic cancer research on the IUB campus and in the state of Indiana.
CSD Focus Areas
- Gene Expression profiling. Our understanding of development and disease would be significantly advanced
by generating more complete catalogs of gene expression profiles in isolated tissues and cells. Such catalogs would help
us identify gene regulatory networks and may provide important clues about gene function. Toward these goals, we are
building up IUB's arsenal of technologies to analyze mRNA and protein accumulation patterns as a function of tissue,
developmental stage, and/or genotype. Such technologies will enable, for example, microarray analysis of RNA accumulation
in tissues/cells isolated by laser capture microdissection or by cell sorting; differential in-gel electrophoresis (DIGE)
comparisons of protein populations; and mass spectrometric analysis of proteins and protein mixtures. Gene expression
profiling studies in Drosophila are likely to lead the way, but proposals for profiling studies in other systems and
using alternative approaches are welcome, as are proposals for computational modeling of gene regulatory networks.
Studies in this focus area will intersect with the Center for Genomics and Bioinformatics (CGB), the Center for
Computational Cytomics (CCC), and the Analytical Technology Development Node, and probably with the other research
nodes and centers as well.
- Investigating basic mechanisms of mitosis and identifying small molecule inhibitors of mitosis.
Mitosis lies at the heart of normal cell proliferation and the unregulated proliferation associated with cancerous
cells. Microtubule motors are key regulators of all phases of mitosis. Investigators at IUB and several other
universities are forming a consortium, the Nanomedicine Center on Mitosis, to investigate microtubule motors and
their roles in mitosis. The goals are to develop and use cutting-edge quantitative approaches to a) define motor
mechanisms underlying spindle assembly, chromosome segregation, and cytokinesis on scales ranging from atomic
(0.2 nm) to cellular dimensions (50 um), and b) identify small molecule inhibitors of specific motors, to advance
basic research and as potential anti-cancer therapies. Organisms and cell types currently being investigated
include Drosophila, C. elegans, and cultured human cells. Proposals are invited for motor-mitosis
investigations in these and other organisms/cells, high throughput screening for small molecule inhibitors
of target proteins, development of advanced imaging capabilities that will advance this project, and computational
modeling of mitotic processes. This project will interface with the CSD focus on building basic cancer research
at IUB (see below), the Analytical Technology Development Node, and the Chemical Imaging and Assaying Center.
- Building basic cancer research at IUB. METACyt aims to promote basic cancer research on the IUB campus, encourage collaborations with cancer labs elsewhere in Indiana, and build partnerships with Indiana-based cancer organizations, such as the Walther Cancer Institute. Some potential areas of investigation are signal transduction cascades, cell cycle control, DNA replication and repair, and regulation of gene expression at the levels of DNA methylation and chromatin modification. Proposals in these and other areas must have high cancer relevance. Collaborative efforts are strongly encouraged, especially for investigators who are new to cancer-related research - collaborations may be with basic or clinical cancer labs at any of several Indiana institutions (e.g., IUB, IU School of Medicine, Purdue Cancer Center, or Notre Dame). This focus area will have strong ties to both of the focus areas described above and will likely interface with several other research nodes and technology centers.
