Biology subjects

Jeffrey M. Dick

Publications and source records attributed to Jeffrey M. Dick.

3 recordsLinked to original sources

bioRxiv2016

Proteomic indicators of oxidation and hydration state in colorectal cancer

New integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer (CRC). Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (ZC) can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue [Formula] is computed by writing the overall formation reactions of proteins from basis species. Using reported results from clinical proteomic studies and microbial community profiling, many datasets exhibit higher mean ZC or [Formula] of proteins in carcinoma or adenoma compared to normal tissue. Microbial protein compositions have lower ZC in bacteria enriched in fecal samples from cancer patients. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H2O and fugacity of O2 that reflect the compositional differences. The compositional analysis suggests that a systematic shift in chemical composition is an essential feature of the cancer proteome, and the thermodynamic descriptions show that the observed proteomic transformations could be promoted by microenvironments shifted toward more oxidizing conditions and increased hydration levels.

Biochemistry↗

bioRxiv2015

Chemical integration of proteins in signaling and development

In developing embryos of eukaryotes, varying concentrations and/or duration of exposure to morphogens induce and repress transcription factors (TFs) in a regular order, thereby acting as signals for cell differentiation. I present a chemical thermodynamic model for the formation and degradation of the morphogen Sonic hedgehog (Shh) and the major TFs involved in dorsal-ventral patterning of the vertebrate neural tube. This two-stage model first considers introduction of Shh into a chemically defined (oxidizing) environment. As the system is driven away from metastable equilibrium, the TFs progressively become more stable than Shh, as indicated by comparison of the calculated overall energies of formation (chemical affinity). In the second stage, a gradual return to metastable equilibrium with Shh drives transitions in the relative stabilities of the TFs that follow the experimental patterns of TF expression. At the intracellular level, the major proteins in the signal transduction network show a metastability progression among reactions of Shh and its cell-surface receptor and the intracellular Gli proteins that act as activators and repressors of transcription. If the endocytosis and degradation of receptor-ligand complexes are coupled to localized protein translation, the consequent thermodynamic constraints may represent a high-level source of specificity that coexists with molecular mechanisms of signal transduction.

Biochemistry↗

bioRxiv2014

Average oxidation state of carbon in proteins

The degree of oxidation of carbon atoms in organic molecules depends on the covalent structure. In proteins, the average oxidation state of carbon (ZC) can be calculated as an elemental ratio from the chemical formula. To investigate oxidation-reduction (redox) patterns, groups of proteins from different subcellular locations and phylogenetic divisions were selected for comparison. Extracellular proteins of yeast have a relatively high oxidation state of carbon, corresponding with oxidizing conditions outside of the cell. However, an inverse relationship between ZC and redox potential occurs between the endoplasmic reticulum and cytoplasm; this trend is interpreted as resulting from overall coupling of protein turnover to the formation of a lower glutathione redox potential in the cytoplasm. In Rubisco homologues, lower ZC tends to occur in organisms with higher optimal growth temperature, and there are broad changes in ZC in whole-genome protein compositions in microbes from different environments. Energetic costs calculated from thermodynamic models suggest that thermophilic organisms exhibit molecular adaptation to not only high temperature but also the reducing nature of many hydrothermal fluids. A view of protein metabolism that depends on the chemical conditions of cells and environments raises new questions linking biochemical processes to changes on evolutionary timescales.

Biochemistry↗