Cavallaro, Massimo, Wang, Yuexuan, Hebenstreit, Daniel and Dutta, Ritabrata

Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system’s dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.

Royal Society Open Science. August 2023

Kelsey Cremin, Gabriel N Meloni, Dimitrios Valavanis, Orkun S Soyer and Patrick R Unwin

Ultramicroelectrode (UME), or, equivalently, microelectrode, probes are increasingly used for single-cell measurements of cellular properties and processes, including physiological activity, such as metabolic fluxes and respiration rates. Major challenges for the sensitivity of such measurements include: (i) the relative magnitude of cellular and UME fluxes (manifested in the current); and (ii) issues around the stability of the UME response over time. To explore the extent to which these factors impact the precision of electrochemical cellular measurements, we undertake a systematic analysis of measurement conditions and experimental parameters for determining single cell respiration rates via the oxygen consumption rate (OCR) in single HeLa cells. We provide a set of model-based suggestions for improving these measurements in the future but highlight that extraordinary improvements in the stability and precision of SECM measurements will be required if single cell OCR measurements are to be realized.

ACS Measurement Science. July 2023

Masahiro Oka, Mayumi Otani, Yoichi Miyamoto, Rieko Oshima, Jun Adachi, Takeshi Tomonaga, Munehiro Asally, Yuya Nagaoka, Kaori Tanaka, Atsushi Toyoda, Kazuki Ichikawa, Shinichi Morishita, Kyoichi Isono, Haruhiko Koseki, Ryuichiro Nakato, Yasuyuki Ohkawa, Yoshihiro Yoneda

NUP98 and NUP214 form chimeric fusion proteins that assemble into phase-separated nuclear bodies containing CRM1, a nuclear export receptor. However, these nuclear bodies' function in controlling gene expression remains elusive. Here, we demonstrate that the nuclear bodies of NUP98::HOXA9 and SET::NUP214 promote the condensation of mixed lineage leukemia 1 (MLL1), a histone methyltransferase essential for the maintenance of HOX gene expression. Collectively, our results show that the phase-separated nuclear bodies of nucleoporin fusion proteins can enhance the activation of target genes by promoting the condensation of MLL1/CRM1 and rearrangement of the 3D genome structure.

Cell Reports. July 2023

Rory Osborne, Laura Rehneke, Silke Lehmann, Jemma Roberts, Melina Altmann, Stefan Altmann, Yingqi Zhang, Eva Köpff, Ana Dominguez-Ferreras, Emeka Okechukwu, Chrysi Sergaki, Charlotte Rich-Griffin, Vardis Ntoukakis, Ruth Eichmann, Weixing Shan, Pascal Falter-Braun & Patrick Schäfer

The mechanisms of symbiont-mediated beneficial effects and similarities and differences to pathogen strategies are mostly unknown. Here, we use 106 (effector-) proteins, secreted by the symbiont Serendipita indica (Si) to modulate host physiology, to map interactions with Arabidopsis thaliana host proteins. Using integrative network analysis, we show significant convergence on target-proteins shared with pathogens and exclusive targeting of Arabidopsis proteins in the phytohormone signalling network. Functional in planta screening and phenotyping of Si effectors and interacting proteins reveals previously unknown hormone functions of Arabidopsis proteins and direct beneficial activities mediated by effectors in Arabidopsis. Thus, symbionts and pathogens target a shared molecular microbe-host interface. At the same time Si effectors specifically target the plant hormone network and constitute a powerful resource for elucidating the signalling network function and boosting plant productivity.

Nature Communications. July 2023

Irnia Nurika, Nurul Azizah, Sri Suhartini, Young Hoon Jung, Guy C. Barker

The efficient utilization of all of the key lignocellulosic biomass residues is important for the development of an integrated biorefineries uassing this as its feedstock. In this study, a process involving a simultaneous pre-treatement process with anaerobic digestion (AD) were implemented for processing oil palm empty fruit bunches (OPEFB) in order to produced both vanillin and methane. The study confirms that multiple products can effectively be isolated using a fungal preatreatment of lignocellulosic OPEFB followed by anerobic fermentation of biomass residual thus maximizing the potential returns and reducing environmentally impacts compared to other pretreatments.

Waste & Biomass Valorization. June 2023

David M. Edwards, Philip Davies and Daniel Hebenstreit

Despite the recent rise of RNA-seq datasets combining single-cell (sc) resolution with 4-thiouridine (4sU) labelling, analytical methods exploiting their power to dissect transcriptional bursting are lacking. Here, we present a mathematical model and Bayesian inference implementation to facilitate genome-wide joint parameter estimation and confidence quantification (R package: burstMCMC). We demonstrate that, unlike conventional scRNA-seq, 4sU scRNA-seq resolves temporal parameters and furthermore boosts inference of dimensionless parameters via a synergy between single-cell resolution and 4sU labelling. We apply our method to published 4sU scRNA-seq data and linked with ChIP-seq data, we uncover previously obscured associations between different parameters and histone modifications.

Genome Biology. June 2023