Synergistic Communication between CD4+ T Cells and Monocytes Impacts the Cytokine Environment.

Physiological cytokine environments arise from factors produced by diverse cell types in coordinated concert. Understanding the contributions of each cell type in the context of cell-cell communication is important for effectively designing disease modifying interventions. Here, we present multi-plexed measurement of 48 cytokines from a coculture system of primary human CD4+ T cells and monocytes across a spectrum of stimuli and for a range of relative T cell/monocyte compositions, coupled with corresponding measurements from PBMCs and plasma from the same donors.

Network analysis of differential Ras isoform mutation effects on intestinal epithelial responses to TNF-α.

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine that can elicit distinct cellular behaviors under different molecular contexts. Mitogen activated protein kinase (MAPK) pathways, especially the extracellular signal-regulated kinase (Erk) pathway, help to integrate influences from the environmental context, and therefore modulate the phenotypic effect of TNF-α exposure. To test how variations in flux through the Erk pathway modulate TNF-α-elicited phenotypes in a complex physiological environment, we exposed mice with different Ras mutations (K-Ras activation, N-Ras activation, and N-Ras ablation) to TNF-α and observed phenotypic and signaling changes in the intestinal epithelium.

Prediction of calcite morphology from computational and experimental studies of mutations of a de novo-designed peptide.

Many organisms use macromolecules, often proteins or peptides, to control the growth of inorganic crystals into complex materials. The ability to model peptide-mineral interactions accurately could allow for the design of novel peptides to produce materials with desired properties. Here, we tested a computational algorithm developed to predict the structure of peptides on mineral surfaces.

De novo design of peptide-calcite biomineralization systems.

Many organisms produce complex, hierarchically structured, inorganic materials via protein-influenced crystal growth--a process known as biomineralization. Understanding this process would shed light on hard-tissue formation and guide efforts to develop biomaterials. We created and tested a computational method to design protein-biomineralization systems.