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Samaroo, J.

Publications and source records attributed to Samaroo, J..

3 recordsLinked to original sources

Motile and matrix-producing cells drive distinct modes of cell-scale motion in Bacillus subtilis colonies

The physics of cell motion and growth drives the expansion of groups of cells including bacterial colonies. Under different conditions, many species of bacteria grow with strikingly different dynamics, which can arise from the physics of constituent cells. For example, on low-percentage agar substrates, colonies often expand rapidly via motility as swarms, while on higher percentage substrates, biofilms expand slowly due to growth and pressure. However, in bacterial species Bacillus subtilis, both swarm and biofilm phenotypes contain differentiated cells in both the motile state and the matrix-producing state, provoking the question: how does phenotypic heterogeneity influence the cell-level motions that drive development? To answer this question, we used a bead-tracking assay in which we follow the motion of cell-sized fluorescent beads embedded in growing B. subtilis colonies. By being pushed due to their interactions with cells, beads passively report on local cell motion. We found that, in rapidly expanding swarms, bead motion was bimodal: some beads moved rapidly and diffusively, while others appeared to be slow or stationary. However, after following the seemingly trapped beads over many hours, we found that the beads in fact moved slowly and ballistically. In biofilms grown on higher percentage agar, we found that some beads were trapped, moving sub-diffusively over the course of biofilm growth, while others moved ballistically. We hypothesized that slow, ballistic bead motion in both swarms and biofilms was driven by groups of radially expanding matrix-producing cells. To test this hypothesis, we performed bead tracking experiments in colonies formed by regulatory mutant strains that were locked into motility or matrix production. In swarms of motile-only cells, we observed fast, diffusive bead motion with no population of slow, ballistic beads. In matrix-only biofilms, we observed that ballistic motion was heavily favored compared to wild type. These results support the hypothesis that expanding clusters of matrix cells drive slow, ballistic motion at the cellular scale during colony growth. Our results demonstrate that heterogeneous cell phenotypes contribute to heterogeneous local physics in bacterial colonies, influencing the distributions of cellular phenotypes.

biophysics↗

Improving the computation efficiency of polygenic risk score modeling: Faster in Julia

To enable large-scale application of polygenic risk scores in a computationally efficient manner we translate a widely used polygenic risk score construction method, Polygenic Risk Score - Continuous Shrinkage (PRS-CS), to the Julia programing language, PRS.jl. On nine different traits with varying genetic architectures, we demonstrate that PRS.jl maintains accuracy of prediction while decreasing the average run time by 5.5x. Additional programmatic modifications improve usability and robustness. This freely available software substantially improves work flow and democratizes utilization of polygenic risk scores by lowering the computational burden of the PRS-CS method.

genetics↗

Diversification of Transcription Factor NF-κB in Protists

In this report, we investigate the evolution of transcription factor NF-{kappa}B by examining its structure, activity, and regulation in two protists using phylogenetic, cellular, and biochemical techniques. In Capsaspora owczarzaki (Co), we find that full-length NF-{kappa}B has an N-terminal DNA-binding domain and a C-terminal Ankyrin (ANK) repeat inhibitory domain, and its DNA-binding activity is more similar to metazoan NF-{kappa}B rather than Rel proteins. As with mammalian NF-{kappa}B proteins, removal of the ANK repeats is required for Co-NF-{kappa}B to enter the nucleus, bind DNA, and activate transcription. However, C-terminal processing of Co-NF-{kappa}B is not induced by co-expression of IKK in human cells. Exogenously expressed Co-NF-{kappa}B localizes to the nucleus in Co cells. NF-{kappa}B mRNA and DNA-binding levels differ across three life stages of Capsaspora, suggesting distinct roles for NF-{kappa}B in these life stages. RNA-seq and GO analyses identify possible gene targets and biological functions of Co-NF-{kappa}B. We also show that three NF-{kappa}B-like proteins from the choanoflagellate Acanthoeca spectabilis (As) all consist of primarily the N-terminal conserved Rel Homology domain sequences of NF-{kappa}B, and lack C-terminal ANK repeats. All three As-NF-{kappa}B proteins constitutively enter the nucleus of human and Co cells, but differ in their DNA-binding and transcriptional activation activities. Furthermore, all three As-NF-{kappa}B proteins can form heterodimers, indicating that NF-{kappa}B diversified into multi-subunit families at least two times during evolution. Overall, these results present the first functional characterization of NF-{kappa}B in a taxonomic kingdom other than Animalia and provide information about the evolution and diversification of this biologically important transcription factor. SignificanceThese results represent the first functional characterization of the biologically important transcription factor NF-{kappa}B in a taxonomic kingdom other than Animalia. As such, they provide information on the evolutionary origins and basal diversification of NF-{kappa}B outside of metazoans. These results suggest that NF-{kappa}B plays life stage-specific roles in Capsaspora, the closest unicellular ancestor to all metazoans. Finally, the analysis of three NF-{kappa}B proteins in a single choanoflagellate indicates that choanoflagellates have subclasses of NF-{kappa}Bs, which can form heterodimers, suggesting that NF-{kappa}B subunit expansion and diversification has occurred at least twice in evolution.

cell biology↗