Biology subjects

Beller, M.

Publications and source records attributed to Beller, M..

3 recordsLinked to original sources

bioRxiv2023

Physiological constraints limiting the growth of Drosophila larvae

The phenotype of organisms is the result of complex interactions between physiology, developmental conditions, and intra-organismic processes, such as metabolism and genetic adaptation. Organisms pursue various developmental strategies that depend on factors such as available resources. How organisms regulate and control critical developmental principles is not fully understood. In this study, we investigated the dynamic development of Drosophila melanogaster larvae through in vitro and in silico experiments. First, we enhanced the larval metabolic network FlySilico and its parameters using growth and metabolite measurements. Subsequently, we established a dynamic flux balance analysis approach and incorporated spatial physiological information from the larval gut to improve the prediction results. We successfully predicted larval growth on different media and developmental critical processes, such as the emergence of larval metamorphosis. This expands the ability to investigate and understand the process of the larval critical weight and, furthermore, the influence of critical developmental processes of multicellular organisms on metabolism. Thus, we present an approach to understand the development, metabolism, and the role of physiology in the development of multicellular organisms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/572459v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@ad726corg.highwire.dtl.DTLVardef@1334d52org.highwire.dtl.DTLVardef@1197e9aorg.highwire.dtl.DTLVardef@c6ef99_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2020

Sequestration to lipid droplets promotes histone availability by preventing turnover of excess histones

Because dearth and overabundance of histones result in cellular defects, histone synthesis and demand are typically tightly coupled. In Drosophila embryos, histones H2B/H2A/H2Av accumulate on lipid droplets (LDs), cytoplasmic fat storage organelles. Without this binding, maternally provided H2B/H2A/H2Av are absent; however, the molecular basis of how LDs ensure histone storage is unclear. Using quantitative imaging, we uncover when during oogenesis these histones accumulate, and which step of accumulation is LD-dependent. LDs originate in nurse cells and are transported to the oocyte. Although H2Av accumulates on LDs in nurse cells, the majority of the final H2Av pool is synthesized in oocytes. LDs promote intercellular transport of the histone-anchor Jabba and thus its presence in the ooplasm. Jabba prevents ooplasmic H2Av from degradation, safeguarding the H2Av stockpile. Our findings provide insight into the mechanism for establishing histone stores during Drosophila oogenesis and shed light on the function of LDs as protein-sequestration sites.

cell biology↗

bioRxiv2016

Predicting gene expression level in E. coli from mRNA sequence information

MotivationThe accurate characterization of the translational mechanism is crucial for enhancing our understanding of the relationship between genotype and phenotype. In particular, predicting the impact of the genetic variants on gene expression will allow to optimize specific pathways and functions for engineering new biological systems. In this context, the development of accurate methods for predicting translation efficiency from the nucleotide sequence is a key challenge in computational biology.\n\nMethodsIn this work we present PGExpress, a binary classifier to discriminate between mRNA sequences with low and high translation efficiency in E. coli. PGExpress algorithm takes as input 12 features corresponding to RNA folding and anti-Shine-Dalgarno hybridization free energies. The method was trained on a set of 1,772 sequence variants (WT-High) of 137 essential E. coli genes. For each gene, we considered 13 sequence variants of the first 33 nucleotides encoding for the same amino acids followed by the superfolder GFP. Each gene variant is represented sequence blocks that include the Ribosome Binding Site (RBS), the first 33 nucleotides of the coding region (C33), the remaining part of the coding region (CC), and their combinations.\n\nResultsOur logistic regression-based tool (PGExpress) was trained using a 20-fold gene-based cross-validation procedure on the WT-High dataset. In this test PGExpress achieved an overall accuracy of 74%, a Matthews correlation coefficient 0.49 and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.81. Tested on 3 sets of sequences with different Ribosome Binding Sites, PGExpress reaches similar AUC. Finally, we validated our method by performing in-house experiments on five newly generated mRNA sequence variants. The predictions of the expression level of the new variants are in agreement with our experimental results in E. coli.\n\nAvailabilityhttp://folding.biofold.org/pgexpress\n\nContactmarkus.kollmann@hhu.de, emidio.capriotti@unibo.it

bioinformatics↗