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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

De novo designed protein inhibitors of amyloid aggregation and seeding

Neurodegenerative diseases are characterized by the pathologic accumulation of aggregated proteins. Known as amyloid, these fibrillar aggregates include proteins such as tau and amyloid-β (Aβ) in Alzheimer’s disease (AD) and alpha-synuclein (αSyn) in Parkinson’s disease (PD). The development and spread of amyloid fibrils within the brain correlates with disease onset and progression, and inhibiting amyloid formation is a possible route toward therapeutic development. Recent advances have enabled the determination of amyloid fibril structures to atomic-level resolution, improving the possibility of structure-based inhibitor design. In this work, we use these amyloid structures to design inhibitors that bind to the ends of fibrils, “capping” them so as to prevent further growth. Using de novo protein design, we develop a library of miniprotein inhibitors of 35 to 48 residues that target the amyloid structures of tau, Aβ, and αSyn. Biophysical characterization of top in silico designed inhibitors shows they form stable folds, have no sequence similarity to naturally occurring proteins, and specifically prevent the aggregation of their targeted amyloid-prone proteins in vitro. The inhibitors also prevent the seeded aggregation and toxicity of fibrils in cells. In vivo evaluation reveals their ability to reduce aggregation and rescue motor deficits in Caenorhabditis elegans models of PD and AD.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

A periplasmic zinc capture protein enhances the resistance of Neisseria gonorrhoeae to nutritional immunity

During microbial infection, mammalian hosts reduce the availability of free metals such as zinc in a process known as nutritional immunity. Pathogens counteract nutritional immunity by expressing gene products that enhance growth in metal-limited conditions. One of the most transcriptionally induced genes in zinc-limited Neisseria gonorrhoeae , ngo1049, encodes a DUF4198 family protein we have named Zcp. This family of proteins is widely distributed in Gram-negative bacteria. Here, we provide the first structural, biochemical, and functional characterization of a DUF4198 protein. Zcp is a periplasmic, homodimeric substrate-binding protein (SBP), which binds one zinc ion per subunit with submicromolar affinity. We identified a zinc binding pocket in each subunit, composed of three histidine residues. Zcp enables maximal growth of N. gonorrhoeae in zinc-limited conditions but is dispensable for zinc uptake, in contrast to the cluster A-I SBP ZnuA, which is required for zinc import. The growth defect of zcp mutant N. gonorrhoeae is rescued by zinc supplementation. Zcp associates with proteins with roles in maintaining cell envelope integrity, and N. gonorrhoeae lacking zcp is more sensitive to envelope-targeting antimicrobials. Zcp enables infectivity of human epithelial cells and neutrophils by zinc-limited N. gonorrhoeae . We conclude that N. gonorrhoeae produces Zcp to buffer periplasmic zinc, which enables ZnuA to balance import of different metals and ensures the bioavailability of zinc for extracytoplasmic zinc-requiring proteins, as part of the coordinated response to host-imposed nutritional immunity.

Liyayi, Ian K. [Department of Microbiology, Immuno↗
DOE OSTI2022

Characterizing proteases in sorghum drought response using activity-based protein profiling (ABPP)

Sorghum (Sorghum bicolor) is a C4 grass species that is a major food and bioenergy crop grown worldwide. Understanding the response of sorghum to climate change is therefore critical to future sustainable food and bioenergy production. Major advancements in genome sequencing have provided a wealth of genomic data for DOE-relevant plant species, but the functions of many of these genes remain unknown. Genotype to phenotype characterization of sorghum and other bioenergy crops is needed to identify key genes responsible for plant resilience to drought and other environmental stressors. Proteases, which modulate protein degradation and cellular signaling processes by catalyzing the hydrolysis of proteins into smaller proteins, peptides, or amino acids, are highly implicated in plant drought stress responses. We developed a method for using activity-based protein profiling (ABPP) of selected protease activities (serine and cysteine proteases) to characterize drought stress responses in sorghum roots and leaves. Analysis of these ABPP data identified several known serine and cysteine proteases as well as uncharacterized sorghum proteins which may have protease activities that can be explored in future validation studies.

09 BIOMASS FUELS↗
DOE OSTI2024

Modulating metal-centered dimerization of a lanthanide chaperone protein for separation of light lanthanides

Elucidating details of biology’s selective uptake and trafficking of rare earth elements, particularly the lanthanides, has the potential to inspire sustainable biomolecular separations of these essential metals for myriad modern technologies. Here, we biochemically and structurally characterize Methylobacterium (Methylorubrum) extorquens LanD, a periplasmic protein from a bacterial gene cluster for lanthanide uptake. This protein provides only four ligands at its surface-exposed lanthanide-binding site, allowing for metal-centered protein dimerization that favors the largest lanthanide, La III . However, the monomer prefers Nd III and Sm III , which are disfavored lanthanides for cellular utilization. Structure-guided mutagenesis of a metal-ligand and an outer-sphere residue weakens metal binding to the LanD monomer and enhances dimerization for Pr III and Nd III by 100-fold. Selective dimerization enriches high-value Pr III and Nd III relative to low-value La III and Ce III in an all-aqueous process, achieving higher separation factors than lanmodulins and comparable or better separation factors than common industrial extractants. Finally, we show that LanD interacts with lanmodulin (LanM), a previously characterized periplasmic protein that shares LanD’s preference for Nd III and Sm III . Our results suggest that LanD’s unusual metal-binding site transfers less-desirable lanthanides to LanM to siphon them away from the pathway for cytosolic import. The properties of LanD show how relatively weak chelators can achieve high selectivity, and they form the basis for the design of protein dimers for separation of adjacent lanthanide pairs and other metal ions.

lanthanide biochemistry↗
DOE OSTI2022

Study of Protein Dynamics via Neutron Spin Echo Spectroscopy

Most human body proteins' activity and functionality are related to configurational changes of entire subdomains within the protein crystal structure. The crystal structures build the basis for any calculation that describes the structure or dynamics of a protein, most of the time with strong geometrical restrictions. However, these restrictions from the crystal structure are not present in the solution. The structure of the proteins in the solution may differ from the crystal due to rearrangements of loops or subdomains on the pico to nanosecond time scale (i.e., the internal protein dynamics time regime). This study describes how slow motions on timescales of several tens of nanoseconds can be accessed using neutron scattering. In particular, the dynamical characterization of two major human proteins, an intrinsically disordered protein that lacks a well-defined secondary structure and a classical antibody protein, is addressed by neutron spin echo spectroscopy (NSE) combined with a wide range of laboratory characterization methods. Further insights into protein domain dynamics were achieved using mathematical modeling to describe the experimental neutron data and determine the crossover between combined diffusive and internal protein motions. The extraction of the internal dynamic contribution to the intermediate scattering function obtained from NSE, including the timescale of the various movements, allows further vision into the mechanical properties of single proteins and the softness of proteins in their nearly natural environment in the crowded protein solution.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Light Energy Transduction in Green Sulfur Bacteria

Green sulfur bacteria (GSB) are exquisitely adapted for growth at extraordinarily low light intensities. They are important primary producers of biomass in many anoxic environments, and they contribute significantly to the biogeochemical cycling of carbon, nitrogen, and sulfur on Earth. Green bacteria more generally share the property of using chlorosomes for light-harvesting, and these unusual organelles have many unique features. These include the presence of a monolayer lipid-protein envelope, self-assembling bacteriochlorophylls (BChl) in which pigment-pigment interactions predominate, and the presence of redox components ([2Fe-2S] ferredoxins and quinones) that play a role in regulating excitation energy transfer to the type-1 homodimeric reaction centers. The reaction centers of GSB are related to Photosystem I of cyanobacteria and higher plants but also exhibit several unique structural and functional features. The long-term objectives of this research program are to understand the structure, functions, and biogenesis of the chlorosomes, reaction centers, and electron transport chains that carry out the photochemical transduction of light energy into chemical energy in the model green sulfur bacterium, Chlorobaculum (formerly Chlorobium) tepidum. Over a period of 26 years, we characterized chlorosomes in detail. We identified the proteins in the chlorosome envelopes of diverse organisms, identified the nearest neighbors of those proteins, and characterized the chlorosomes of mutant strains lacking one to five of these proteins. After the genome sequence of Cba. tepidum became available, we identified all genes encoding enzymes for BChl a , BChl c/d/e/ƒ , and Chl a biosynthesis Cba. tepidum . We additionally identified all genes encoding enzymes for carotenoid biosynthesis. By constructing a bchQRU mutant strain that produces [Et, Me]-BChl d , together with collaborators who are specialists in solid-state NMR and cryo-electron microscopy, we solved the structure of the BChls in chlorosomes. Using similar methods and chlorosomes containing [Et, Me]-BChl c , we then showed that alternative structures were possible using the same syn-anti BChl dimer. The structures were refined by introducing spectroscopic data from single-chlorosome measurements. Over the course of this project, we sequenced the genomes of approximately twenty GSB strains, which provided important information for comparative analyses. Through analyses of metagenomic data from Mushroom and Octopus Springs in Yellowstone National Park, we identified a novel chlorophototroph belonging to the phylum Acidobacteriota. We successfully isolated an axenic culture of this organism. We characterized the photosynthetic apparatus of this bacterium, named Chloracidobacterium thermophilum, in significant detail, in particular its type-1, homodimeric reaction centers. Surprisingly, these reaction centers contain three types of Chls, BChl a , Chl a , and Zn-BChl a' . We showed that a dimer of Zn-BChl a' is the primary donor and Chl a the primary acceptor of electrons in this reaction center by using advanced spectroscopic techniques. We isolated eight additional strains of Chloracidobacterium spp. from Mushroom Spring and Rupite hot springs in Bulgaria. Comparative genomes showed that these represent three species, Cab. thermophilum , Cab. aggregatum , and Cab. validum . By applying comparative genomics, genetic, biochemical biophysical and physiological approaches to study green bacteria, we produced a wealth of new information about the remarkable light-harvesting and energy transduction capabilities of these poorly characterized microorganisms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Validation and functional characterization of transcription factors in wheat using cell-free protein expression and high-throughput sequencing technologies

Transcription factors (TFs) are critical biomolecules that control and regulate gene expression in every organism. In wheat, there are 3,606 genes annotated as putative TFs which are primarily uncharacterized. In this work, using a DAP-seq approach, we have validated and characterized a select number of TFs (5bl and 5dl) belonging to GeBP family of proteins, responsible for plant cellular growth, development, and differentiation. We found that top DNA binding motifs for 5bl and 5dl are (G/T)N(T/G)GTGGT and (C/G)AA(C/G)AA respectively. These motifs/peaks are enriched in the promoter regions of the genes, which are associated with rRNA biogenesis and protein maturation pathways. This study is also a first demonstration that DAP-seq can be applied for such a complex and large genome such as wheat.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Dual Targeting Factors Are Required for LXG Toxin Export by the Bacterial Type VIIb Secretion System

Bacterial type VIIb secretion systems (T7SSb) are multisubunit integral membrane protein complexes found in Firmicutes that play a role in both bacterial competition and virulence by secreting toxic effector proteins. The majority of characterized T7SSb effectors adopt a polymorphic domain architecture consisting of a conserved N-terminal Leu-X-Gly (LXG) domain and a variable C-terminal toxin domain. Recent work has started to reveal the diversity of toxic activities exhibited by LXG effectors; however, little is known about how these proteins are recruited to the T7SSb apparatus. In this work, we sought to characterize genes encoding domains of unknown function (DUFs) 3130 and 3958, which frequently cooccur with LXG effector-encoding genes. Using coimmunoprecipitation-mass spectrometry analyses, in vitro copurification experiments, and T7SSb secretion assays, we found that representative members of these protein families form heteromeric complexes with their cognate LXG domain and in doing so, function as targeting factors that promote effector export. Additionally, an X-ray crystal structure of a representative DUF3958 protein, combined with predictive modeling of DUF3130 using AlphaFold2, revealed structural similarity between these protein families and the ubiquitous WXG100 family of T7SS effectors. Interestingly, we identified a conserved FxxxD motif within DUF3130 that is reminiscent of the YxxxD/E “export arm” found in mycobacterial T7SSa substrates and mutation of this motif abrogates LXG effector secretion. Overall, our data experimentally link previously uncharacterized bacterial DUFs to type VIIb secretion and reveal a molecular signature required for LXG effector export.

24 antibacterial toxins↗
DOE OSTI2025

An Integral Activity-Based Protein Profiling Method for Higher Throughput Determination of Protein Target Sensitivity to Small Molecules

Activity-based protein profiling (ABPP) is a chemoproteomic technique that uses small molecule probes to label active enzymes selectively and covalently in complex proteomes. Competitive ABPP, which involves treatment of the active proteome with an analyte of interest, is especially powerful for profiling how small molecules impact specific protein activities. Advances in higher throughput workflows have made it possible to generate extensive competitive ABPP data across diverse biological samples, making this approach highly appealing for characterizing shared and unique proteins affected by perturbations such as drug or chemical exposures. To use the competitive ABPP approach effectively to understand potential adverse effects of chemicals of concern (CoC), a wide range of concentrations may be needed, particularly for chemicals that lack potency or toxicity data. In this work, we present an integral competitive ABPP method that enables target sensitivity determination for different organophosphate (OP) pesticides as model toxicants. Using previously developed OP-ABPs, we optimized conditions for tandem mass tag (TMT) multiplexing of ABPP samples and compared conventional competitive ABPP involving samples at discrete paraoxon concentrations to pooled samples across that same concentration range. We then expanded our approach to compare protein target sensitivities toward two additional OP pesticides, chlorpyrifos oxon and malaoxon. The results showed that differences in integral intensities for the pooled competition sample can be used to evaluate the relative sensitivity of specific proteins without increasing the overall number of samples. For 8 CoC concentrations of interest, this strategy reduced the number of TMT plexes and the corresponding number of LC–MS/MS analyses 3-fold. In conclusion, we envision the integral ABPP (IABPP) method will provide a means to screen diverse chemicals more rapidly to identify both high and low sensitivity protein targets.

activity-based probes↗
DOE OSTI2025

Addressing genome scale design tradeoffs in Pseudomonas putida for bioconversion of an aromatic carbon source

Genome-scale metabolic models (GSMM) are commonly used to identify gene deletion sets that result in growth coupling and pairing product formation with substrate utilization and can improve strain performance beyond levels typically accessible using traditional strain engineering approaches. However, sustainable feedstocks pose a challenge due to incomplete high-resolution metabolic data for non-canonical carbon sources required to curate GSMM and identify implementable designs. Here we address a four-gene deletion design in the Pseudomonas putida KT2440 strain for the lignin-derived non-sugar carbon source, p-coumarate (p-CA), that proved challenging to implement. We examine the performance of the fully implemented design for p-coumarate to glutamine, a useful biomanufacturing intermediate. In this study glutamine is then converted to indigoidine, an alternative sustainable pigment and a model heterologous product that is commonly used to colorimetrically quantify glutamine concentration. Through proteomics, promoter-variation, and growth characterization of a fully implemented gene deletion design, we provide evidence that aromatic catabolism in the completed design is rate-limited by fumarase hydratase (FUM) enzyme activity in the citrate cycle and requires careful optimization of another fumarate hydratase protein (PP_0897) expression to achieve growth and production. A double sensitivity analysis also confirmed a strict requirement for fumarate hydratase activity in the strain where all genes in the growth coupling design have been implemented. Metabolic cross-feeding experiments were used to examine the impact of complete removal of the fumarase hydratase reaction and revealed an unanticipated nutrient requirement, suggesting additional functions for this enzyme. While a complete implementation of the design was achieved, this study highlights the challenge of completely inactivating metabolic reactions encoded by under-characterized proteins, especially in the context of multi-gene edits.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

A Bis(imidazole)-based cysteine labeling tool for metalloprotein assembly

Precise metal-protein coordination by design remains a considerable challenge. Polydentate, high-metal-affinity protein modifications, both chemical and recombinant, can enable metal localization. However, these constructs are often bulky, conformationally and stereochemically ill-defined, or coordinately saturated. Here, we expand the biomolecular metal-coordination toolbox with the irreversible attachment to cysteine of bis(1-methylimidazol-2-yl)ethene (“BMIE”), which generates a compact imidazole-based metal-coordinating ligand. Conjugate additions of small-molecule thiols (thiocresol and N-Boc-Cys) with BMIE confirm general thiol reactivity. The BMIE adducts are shown to complex the divalent metal ions Cu ++ and Zn ++ in bidentate (N 2 ) and tridentate (N 2 S*) coordination geometries. Cysteine-targeted BMIE modification (>90% yield at pH 8.0) of a model protein, the S203C variant of carboxypeptidase G2 (CPG2), measured with ESI-MS, confirms its utility as a site-selective bioconjugation method. ICP-MS analysis confirms mono-metallation of the BMIE-modified CPG2 protein with Zn ++ , Cu ++ , and Co ++ . EPR characterization of the BMIE-modified CPG2 protein reveals the structural details of the site selective 1:1 BMIE-Cu ++ coordination and symmetric tetragonal geometry under physiological conditions and in the presence of various competing and exchangeable ligands (H 2 O/HO – , tris, and phenanthroline). An X-ray protein crystal structure of BMIE-modified CPG2-S203C demonstrates that the BMIE modification is minimally disruptive to the overall protein structure, including the carboxypeptidase active sites, although Zn ++ metalation could not be conclusively discerned at the resolution obtained. The carboxypeptidase catalytic activity of BMIE-modified CPG2-S203C was also assayed and found to be minimally affected. Finally, these features, combined with ease of attachment, define the new BMIE-based ligation as a versatile metalloprotein design tool, and enable future catalytic and structural applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Frameshifting Stimulatory Sequence Induces Large Structural Change of Ribosomal Proteins When Bound to E. coli Ribosomes

Biological macromolecular machines occupy a continuum of structural conformations to perform cellular tasks. Mapping this conformational space provides an insight into its functionality. While the cryo-electron microscopy resolution revolution has expanded our ability to characterize the conformational continuums, there are obstacles in structurally characterizing regions of high flexibility. These technical barriers have impeded characterization of flexible ribosomal proteins when the ribosome is interacting with mRNA stem-loop structures such as a frameshifting stimulatory sequence (FSS). Small-angle neutron/X-ray scattering and electron microscopy were used to study ribosomal samples and compared structural differences between a ribosome that is bound to an FSS stem-loop compared to a ribosome bound to linear mRNA. This comparison shows that a large protein stalk elongates by 22% when the 70S interacts with an mRNA stem-loop. Finally, our results suggest that ribosomal proteins have extensive flexibility and may influence important ribosomal mechanisms, such as those that involve FSS.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Five key aspects of metaproteomics as a tool to understand functional interactions in host-associated microbiomes

Host-associated microbial communities (microbiomes) play critical roles in human, animal, and plant health and development. However, interactions between the host, members of the microbiome, and invading pathogens are in most cases still poorly understood. Such interactions are multidimensional and can alter the taxonomic composition and/or the functional metabolic activities of the microbiome in response to disease or treatment conditions. For example, after 2 days of antibiotic treatment, the mouse gut microbiome is altered and more susceptible to invasion by the pathogen Clostridioides difficile. Studies of these multidimensional interactions have been fueled by the ability to use high-throughput sequencing of phylogenetic marker genes to profile microbial community composition and shotgun metagenomics to profile functional potential. However, many protein-coding genes predicted from metagenomes are not necessarily expressed under a given condition, and thus, it is difficult to assess the activities and functional interactions in microbial communities based on DNA sequencing data alone. The physiological and pathological processes expressed in these communities under specific conditions are better reflected by the abundances of transcripts or proteins. In this Pearl, we provide a brief introduction to metaproteomics, which is a tool for the large-scale analysis of proteins in microbiomes that allows researchers to address a diversity of questions related to functions and interactions in microbiomes. The term “metaproteomics” was first used in 2004 for “the large-scale characterization of the entire protein complement of environmental microbiota at a given point in time”, and since then, a large array of metaproteomics approaches have been developed. Our objective in this Pearl is to highlight what we feel are 5 essential elements to be considered for a metaproteomics research campaign and to introduce nonexpert readers to the topic without going into too much technical detail.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Identifying Receptor Kinase Substrates Using an 8000 Peptide Kinase Client Library Enriched for Conserved Phosphorylation Sites

In eukaryotic organisms, protein kinases regulate diverse protein activities and signaling pathways through phosphorylation of specific protein substrates. Isolating and characterizing kinase substrates is vital for defining downstream signaling pathways. The kinase-client (KiC) assay is an in vitro synthetic peptide LC-MS/MS phosphorylation assay that has enabled identification of protein substrates (i.e., clients) for various protein kinases. For example, previous use of a 2100-member (2k) peptide library identified substrates for the extracellular ATP receptor-like kinase, P2K1. Many P2K1 clients were confirmed by additional in vitro and in planta studies, including integrin-linked kinase 4, for which we provide the evidence herein. In addition, we developed a new KiC peptide library containing 8000 (8k) peptides based on phosphorylation sites primarily from Arabidopsis thaliana datasets. The 8k peptides are enriched for sites with conservation in other angiosperm plants, with the paired goals of representing functionally conserved sites and usefulness for screening kinases from diverse plants. Screening the 8k library with the active P2K1 kinase domain identified 177 phosphopeptides, including calcineurin B–like protein and G protein alpha subunit 1, which functions in cellular calcium signaling. We confirmed that P2K1 directly phosphorylates calcineurin B–like protein and G protein alpha subunit 1 through in vitro kinase assays. This expanded 8k KiC assay will be a useful tool for identifying novel substrates across diverse plant protein kinases, ultimately facilitating the exploration of previously undiscovered signaling pathways.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Ancient origins of allosteric activation in a Ser-Thr kinase

A myriad of cellular events are regulated by allostery; therefore, evolution of this process is of fundamental interest. Here, we use ancestral sequence reconstruction to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2 (targeting protein for Xklp2), to experimentally characterize the evolutionary path of allosteric activation. Autophosphorylation of the activation loop is the most ancient activation mechanism; it is fully developed in the oldest kinase ancestor and has remained stable over 1 billion years of evolution. As the microtubule-associated protein TPX2 appeared, efficient kinase binding to TPX2 evolved, likely owing to increased fitness by virtue of colocalization. Subsequently, TPX2-mediated allosteric kinase regulation gradually evolved. Surprisingly, evolution of this regulation is encoded in the kinase and did not arise by a dominating mechanism of coevolution.

Science & Technology - Other Topics↗
DOE OSTI2024

FatPlants: a comprehensive information system for lipid-related genes and metabolic pathways in plants

Abstract FatPlants, an open-access, web-based database, consolidates data, annotations, analysis results, and visualizations of lipid-related genes, proteins, and metabolic pathways in plants. Serving as a minable resource, FatPlants offers a user-friendly interface for facilitating studies into the regulation of plant lipid metabolism and supporting breeding efforts aimed at increasing crop oil content. This web resource, developed using data derived from our own research, curated from public resources, and gleaned from academic literature, comprises information on known fatty-acid-related proteins, genes, and pathways in multiple plants, with an emphasis on Glycine max, Arabidopsis thaliana, and Camelina sativa. Furthermore, the platform includes machine-learning based methods and navigation tools designed to aid in characterizing metabolic pathways and protein interactions. Comprehensive gene and protein information cards, a Basic Local Alignment Search Tool search function, similar structure search capacities from AphaFold, and ChatGPT-based query for protein information are additional features. Database URL: https://www.fatplants.net/

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

New Views of Old Proteins: Clarifying the Enigmatic Proteome

All human diseases involve proteins, yet our current tools to characterize and quantify them are limited. To better elucidate proteins across space, time, and molecular composition, we provide provocative projections for technologies to meet the challenges that protein biology presents. With a broad perspective, we discuss grand opportunities to transition the science of proteomics into a more propulsive enterprise. Extrapolating recent trends, we offer potential futures for a next generation of disruptive approaches to define, quantify and visualize the multiple dimensions of the proteome, thereby transforming our understanding and interactions with human disease in the coming decade.

59 BASIC BIOLOGICAL SCIENCES↗