Computational protein design attempts to create protein sequences that fold stably into pre-specified structures. Here we compare alignments of designed proteins to alignments of natural proteins and assess how closely designed sequences recapitulate patterns of sequence variation found in natural protein sequences. We design proteins using RosettaDesign, and we evaluate both fixed-backbone des...

Knowledge of intrinsic tumor heterogeneity is vital for understanding of tumor progression mechanisms as well as for providing efficient treatments. In situ proteomic profiling of tumors is a powerful technology with potential to enhance our understanding of tumor biology, but sources of variability due to patient and tumor heterogeneity are poorly understood and are the topic of this investiga...

Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype. For TRAIL (TNF-related apoptosis-inducing ligand) variability manifests itself as dramatic differences in the time between ligand exposure and the sudden activation of the effector caspases that kill cells. However, the contribution of...

We show that the clumpy structure of star-forming regions can naturally explain the fact that 50-70% of GRB afterglows are optical“dark.” We also show that dust echos from the GRB and its afterglow, produced by the clumpy structure of the star-forming region in which the GRB occurs, can lead to temporal variability and peaks in the NIR, optical, and UV lightcurves of GRB afterglows.

Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by ca...

Human respiratory syncytial virus (HRSV) has three surface glycoproteins: small hydrophobic (SH), attachment (G) and fusion (F), encoded by three consecutive genes (SH-G-F). A 270-nt fragment of the G gene is used to genotype HRSV isolates. This study genotyped and investigated the variability of the gene and amino acid sequences of the three surface proteins of HRSV strains collected from 1987...

Homogeneous cell populations can exhibit considerable cell-to-cell variability in protein levels arising from the stochastic nature of the gene-expression process. In particular, transcriptional bursting of mRNAs from the promoter has been implicated as a major source of stochasticity in the expression of many genes. In eukaryotes, transcribed pre-mRNAs have to be exported outside the nucleus a...