Biology subjects

Cenik, E. S.

Publications and source records attributed to Cenik, E. S..

4 recordsLinked to original sources

bioRxiv2025

Inverse-scattering in biological samples via beam-propagation

Multiple scattering limits optical imaging in thick biological samples by scrambling sample-specific information. Physics-based inverse-scattering methods aim to computationally recover this information, often using non-convex optimization to reconstruct the scatter-corrected sample. However, this non-convexity can lead to inaccurate reconstructions, especially in highly scattering samples. Here, we show that various implementation strategies for even the same inverse-scattering method significantly affect reconstruction quality. We demonstrate this using multi-slice beam propagation (MSBP), a relatively simple nonconvex inverse-scattering method that reconstructs a scattering samples 3D refractive-index (RI). By systematically conducting MSBP-based inverse-scattering on both phantoms and biological samples, we showed that an amplitude-only cost function in the inverse-solver, combined with angular and defocus diversity in the scattering measurements, enabled high-quality, fully-volumetric RI imaging. This approach achieved subcellular resolution and label-free 3D contrast across diverse, multiple-scattering samples. These results lay the groundwork for robust use of inverse-scattering techniques to achieve biologically interpretable 3D imaging in increasingly thick, multicellular samples, introducing a new paradigm for deep-tissue computational imaging.

bioengineering↗

bioRxiv2024

Translation efficiency covariation across cell types is a conserved organizing principle of mammalian transcriptomes

Characterizing shared patterns of RNA expression between genes across conditions has led to the discovery of regulatory networks and novel biological functions. However, it is unclear if such coordination extends to translation. Here, we uniformly analyzed 3,819 ribosome profiling datasets from 117 human and 94 mouse tissues and cell lines. We introduce the concept of translation efficiency covariation (TEC), identifying coordinated translation patterns across cell types. We nominate candidate mechanisms driving shared patterns of translation regulation. TEC is conserved across human and mouse cells and uncovers gene functions that are not evident from RNA or protein co-expression. Moreover, our observations indicate that proteins that physically interact are highly enriched for positive covariation at both translational and transcriptional levels. Our findings establish TEC as a conserved organizing principle of mammalian transcriptomes.

bioinformatics↗

bioRxiv2022

Hypodermal ribosome synthesis inhibition induces a nutrition-uncoupled organism-wide growth quiescence

Inter-organ communication is a key aspect of multicellular organismal growth, development, and homeostasis. Importantly, cell-non-autonomous inhibitory cues that limit tissue specific growth alterations are poorly characterized due to limitations of cell ablation approaches. Here, we report a robust system to investigate nutrition-independent organism-wide growth coordination by modulating ribosome biogenesis at distinct steps in a tissue-specific and reversible fashion in Caenorhabditis elegans. We find an organism-wide growth quiescence response upon suppression of ribosome synthesis either by depletion of an RNA polymerase I (Pol I) subunit or either of two critical ribosome biogenesis factors, RRB-1 and TSR-2, which are the chaperone proteins required for assembly of ribosomal proteins, RPL-3 and RPS-26, respectively. The observed organism-wide growth checkpoint is independent of the nutrition-dependent insulin signaling pathways and is not rescued by daf-16(mu86), a bypass mutation that suppresses the starvation-induced quiescence response. Upon systematically exploring tissues involved in this process, we find that inhibition of hypodermal ribosome synthesis is sufficient to trigger an organism-wide growth quiescence response and leads to organism-wide gene expression changes. At the RNA level, we observe over- and under-expression of several tissue-restricted genes in a wide range of cell types, including touch receptor neurons suggesting inter-organ communication upon hypodermis driven ribosome inhibition. At the protein level, we observed over-expression of secreted proteins (CPR-4, TTR family proteins) as well as an organism-wide reduction both in cytosolic and mitochondrial ribosomal proteins in response to hypodermis RNA Pol I depletion. Finally, we find that dense core vesicle secretion specifically from the hypodermis tissue by the unc-31 gene plays a significant role in mediating the quiescence phenotype. Taken together, these results suggest the presence of a nutrition-independent multicellular growth coordination initiated from the hypodermis tissue.

developmental biology↗

bioRxiv2020

Functional and structural basis of extreme non-coding conservation in vertebrate mRNA 5' untranslated regions

The lack of knowledge about extreme conservation in genomes remains a major gap in our understanding of the evolution of gene regulation. While previous findings have mainly focused on the role of extreme conservation at the level of DNA in transcriptional regulation, its implications for RNA biology remains largely unexplored. Here, we reveal an unexpected role of extremely conserved 5UTRs in translational regulation that is linked to the emergence of essential developmental features in vertebrate species. Endogenous deletion of conserved elements within these 5UTRs decreased gene expression at the post-transcriptional level. A large-scale reporter library of extremely conserved 5UTRs revealed the widespread presence of cis-regulatory elements that promote cell-type specific regulation of translation. As these elements function as RNA molecules, further understanding of their potential structures was essential. We therefore developed in-cell mutate-and-map (icM2), a novel methodology that maps RNA structure using high-throughput mutational analysis, previously impossible to perform inside cells. Using icM2, we determined that an extremely conserved 5UTR encodes multiple alternative structures whose relative proportions are actively maintained by ATP-dependent RNA helicases. We further show that each single nucleotide within the extremely conserved element maintains the balance of alternative structures important to control the dynamic range of protein expression. These results explain how extreme sequence conservation can lead to RNA-level biological functions encoded in the untranslated regions of vertebrate genomes.

genetics↗