Biology subjects

Hess, N.

Publications and source records attributed to Hess, N..

4 recordsLinked to original sources

bioRxiv2026

Biomolecular Condensates Dictate the Folding Landscape of Proteins

Protein structure is exquisitely sensitive to the surrounding chemical environment, and many proteins encounter complex environments within cells. Importantly, numerous proteins organize into biomolecular condensates--dense macromolecular assemblies with distinct physicochemical properties. This raises a fundamental question: how does condensation reshape protein structure and dynamics? Here, we investigate how protein folding landscapes are altered inside condensates, using the protein -helix as a model folded domain. Atomistic simulations show that free energy surfaces within condensates differ markedly from those in dilute solution or in the presence of inert crowders. We then use Bayesian optimization to develop a chemically specific, near-atomistic model for quantification of -helical folding and apply it to characterize diverse helices, including -helical domains from the disease-associated proteins TDP43, Annexin A11, and the Androgen Receptor, within condensates of varying physicochemical properties. Our results support a framework in which multivalent interactions drive unfolding while crowding promotes folding, and protein conformational ensembles inside condensates emerge from this balance. Additionally, we show that folding transitions are kinetically frustrated inside condensates because they are coupled to the timescale of contact rearrangement with co-condensate proteins. As such, folding landscapes within condensates are dually sequence-dependent, informed by both the sequence of the folded domain and co-condensate proteins. Together, our work has implications for understanding condensate-mediated proteinopathies, targeting aberrant condensates, and designing condensates to program protein function across scales.

biophysics↗

bioRxiv2024

Challenges in inferring breathing rhythms from olfactory bulb local field potentials

Odors convey useful navigational and episodic information, yet much of the chemical world remains inaccessible without active sampling through sniffing. Respiratory cycles control odor dynamics within the nose, so understanding olfactory bulb (OB) neural dynamics requires accurate respiratory measurements. While respiratory behavior can be measured directly with a variety of chronic methods, these methods are invasive and none are perfectly robust. OB local field potentials (LFPs) have long been known to couple with respiration. Here we investigated whether the precise timing and frequency of respiration can be inferred from OB LFPs. Our results replicate previous findings that OB LFPs across multiple frequency bands align with respiratory cycles. Further, these OB rhythms are locked to time in the respiratory cycle, and not phase. In addition, we show that 2-12 Hz LFP oscillations effectively track sniffing rate. However, a monotonic relationship between LFP-respiratory delay and sniffing rate, which varies across animals, renders the recovery of precise respiratory events challenging. This work underscores the complex and individualized relationship between rodent respiration and OB LFPs, contributing to our understanding of how respiration controls olfaction.

neuroscience↗

bioRxiv2022

One thousand soils for molecular understanding of belowground carbon cycling

While significant progress has been made in understanding global carbon (C) cycling, the mechanisms regulating belowground C fluxes and storage are still uncertain. New molecular technologies have the power to elucidate these processes, yet we have no widespread standardized implementation of molecular techniques. To address this gap, we introduce the Molecular Observation Network (MONet), a decadal vision from the Environmental Molecular Sciences Laboratory (EMSL), to develop a national network for understanding the molecular composition, physical structure, and hydraulic and biological properties of soil and water. These data are essential for advancing the next generation of multiscale Earth systems models. In this paper, we discuss the 1000 Soils Pilot for MONet, including a description of standardized sampling materials and protocols and a use case to highlight the utility of molecular-level and microstructural measurements for assessing the impacts of wildfire on soil. While the 1000 Soils Pilot generated a plethora of data, we focus on assessments of soil organic matter (SOM) chemistry via Fourier-transform ion cyclotron resonance-mass spectrometry and microstructural properties via X-ray Computed Tomography to highlight the effects of recent fire history in forested ecosystems on belowground C cycling. We observed decreases in soil respiration, microbial biomass, and potential enzyme activity in soils with high frequency burns. Additionally, the nominal oxidation state of carbon in SOM increased with burn frequency in surface soils. This results in a quantifiable shift in the molecular signature of SOM and shows that wildfire may result in oxidation of SOM and structural changes to soil pore networks that persist into deeper soils.

ecology↗

bioRxiv2022

MetaboDirect: An Analytical Pipeline for the processing of FTICR-MS-based Metabolomics Data

BackgroundMicrobiomes are now recognized as main drivers of ecosystem function ranging from the oceans and soils to humans and bioreactors. However, a grand challenge in microbiome science is to characterize and quantify the chemical currencies of organic matter (i.e. metabolites) that microbes respond to and alter. Critical to this has been the development of Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), which has drastically increased molecular characterization of complex organic matter samples, but challenges users with hundreds of millions of data points where readily available, user-friendly, and customizable software tools are lacking. ResultsHere, we build on years of analytical experience with diverse sample types to develop MetaboDirect, an open-source, command-line based pipeline for the analysis, visualization, and presentation of metabolomics data by direct injection FTICR-MS after molecular formula assignment has been performed. When compared to all other available FTICR software, MetaboDirect is superior with respect to its compute time as it only requires a single line of code that launches a fully automated framework for the generation and visualization of a wide range of plots, with minimal coding experience required. Among the tools evaluated, MetaboDirect is also uniquely able to automatically generate biochemical transformation networks (ab initio) based on mass differences that provide a comprehensive experimental assessment of metabolite connectives within a given sample or a complex metabolic system, thereby providing important information about the nature of the samples and the set of the microbial reactions or pathways that gave rise to them. Finally, for more experienced users, MetaboDirect allows users to customize plots, outputs, and analyses. ConclusionApplication of MetaboDirect to FTICR-MS-based metabolomics datasets from a marine phage-bacterial infection experiment and a Sphagnum leachate microbiome incubation experiment showcase the exploration capabilities of the pipeline that will enable the FTICR-MS research community to evaluate and interpret their data in greater depth and in less time. It will further advance our knowledge of how microbial communities influence and are influenced by the chemical makeup of the surrounding system. Source code and Users guide of MetaboDirect are freely available through (https://github.com/Coayala/MetaboDirect) and (https://metabodirect.readthedocs.io/en/latest/) respectively.

bioinformatics↗