Protein Sequencing, One Molecule at a Time

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Brendan M. Floyd ◽  
Edward M. Marcotte
Keyword(s):  
Nucleic Acid ◽  
Single Molecule ◽  
Large Scale ◽  
Dynamic Range ◽  
Medical Diagnostics ◽  
Protein Quantification ◽  
Protein Sequencing ◽  
Protein Isoforms ◽  
Annual Review ◽  
Publication Date

Despite tremendous gains over the past decade, methods for characterizing proteins have generally lagged behind those for nucleic acids, which are characterized by extremely high sensitivity, dynamic range, and throughput. However, the ability to directly characterize proteins at nucleic acid levels would address critical biological challenges such as more sensitive medical diagnostics, deeper protein quantification, large-scale measurement, and discovery of alternate protein isoforms and modifications and would open new paths to single-cell proteomics. In response to this need, there has been a push to radically improve protein sequencing technologies by taking inspiration from high-throughput nucleic acid sequencing, with a particular focus on developing practical methods for single-molecule protein sequencing (SMPS). SMPS technologies fall generally into three categories: sequencing by degradation (e.g., mass spectrometry or fluorosequencing), sequencing by transit (e.g., nanopores or quantum tunneling), and sequencing by affinity (as in DNA hybridization–based approaches). We describe these diverse approaches, which range from those that are already experimentally well-supported to the merely speculative, in this nascent field striving to reformulate proteomics. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mechanical Patterning in Animal Morphogenesis

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Yonit Maroudas-Sacks ◽  
Kinneret Keren
Keyword(s):  
Pattern Formation ◽  
Large Scale ◽  
Coarse Grained ◽  
Annual Review ◽  
Publication Date ◽  
Biochemical Processes ◽  
Substantial Progress ◽  
Biological Pattern Formation ◽  
Effective Theories ◽  
Biochemical Signals

Morphogenesis is one of the most remarkable examples of biological pattern formation. Despite substantial progress in the field, we still do not understand the organizational principles responsible for the robust convergence of the morphogenesis process across scales to form viable organisms under variable conditions. Achieving large-scale coordination requires feedback between mechanical and biochemical processes, spanning all levels of organization and relating the emerging patterns with the mechanisms driving their formation. In this review, we highlight the role of mechanics in the patterning process, emphasizing the active and synergistic manner in which mechanical processes participate in developmental patterning rather than merely following a program set by biochemical signals. We discuss the value of applying a coarse-grained approach toward understanding this complex interplay, which considers the large-scale dynamics and feedback as well as complementing the reductionist approach focused on molecular detail. A central challenge in this approach is identifying relevant coarse-grained variables and developing effective theories that can serve as a basis for an integrated framework for understanding this remarkable pattern-formation process. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Gang Research in the Twenty-First Century

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Caylin Louis Moore ◽  
Forrest Stuart
Keyword(s):  
Large Scale ◽  
Criminological Theory ◽  
First Century ◽  
Annual Review ◽  
Publication Date ◽  
Theoretical Frameworks ◽  
Twenty First Century ◽  
State Interventions ◽  
And Behavior ◽  
Analytical Approaches

For nearly a century, gang scholarship has remained foundational to criminological theory and method. Twenty-first-century scholarship continues to refine and, in some cases, supplant long-held axioms about gang formation, organization, and behavior. Recent advances can be traced to shifts in the empirical social reality and conditions within which gangs exist and act. We draw out this relationship—between the ontological and epistemological—by identifying key macrostructural shifts that have transformed gang composition and behavior and, in turn, forced scholars to revise dominant theoretical frameworks and analytical approaches. These shifts include large-scale economic transformations, the expansion of punitive state interventions, the proliferation of the Internet and social media, intensified globalization, and the increasing presence of women and LGBTQ individuals in gangs and gang research. By introducing historically unprecedented conditions and actors, these developments provide novel opportunities to reconsider previous analyses of gang structure, violence, and other related objects of inquiry. Expected final online publication date for the Annual Review of Criminology, Volume 5 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Bacterial Multicellularity: The Biology of Escherichia coli Building Large-Scale Biofilm Communities

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Diego O. Serra ◽  
Regine Hengge
Keyword(s):  
Escherichia Coli ◽  
Large Scale ◽  
Second Messengers ◽  
Emergent Properties ◽  
Annual Review ◽  
Publication Date ◽  
Growth And Survival ◽  
Chemical Gradients ◽  
Life Itself ◽  
Scale Matrix

Biofilms are a widespread multicellular form of bacterial life. The spatial structure and emergent properties of these communities depend on a polymeric extracellular matrix architecture that is orders of magnitude larger than the cells that build it. Using as a model the wrinkly macrocolony biofilms of Escherichia coli, which contain amyloid curli fibers and phosphoethanolamine (pEtN)-modified cellulose as matrix components, we summarize here the structure, building, and function of this large-scale matrix architecture. Based on different sigma and other transcription factors as well as second messengers, the underlying regulatory network reflects the fundamental trade-off between growth and survival. It controls matrix production spatially in response to long-range chemical gradients, but it also generates distinct patterns of short-range matrix heterogeneity that are crucial for tissue-like elasticity and macroscopic morphogenesis. Overall, these biofilms confer protection and a potential for homeostasis, thereby reducing maintenance energy, which makes multicellularity an emergent property of life itself. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Dog Models of Aging

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Audrey Ruple ◽  
Evan MacLean ◽  
Noah Snyder-Mackler ◽  
Kate E. Creevy ◽  
Daniel Promislow
Keyword(s):  
Large Scale ◽  
Mammalian Species ◽  
Annual Review ◽  
Publication Date ◽  
Companion Dogs ◽  
Age Related ◽  
Key Concepts ◽  
Similarities And Differences ◽  
Laboratory Models ◽  
Unique Potential

As the most phenotypically diverse mammalian species that shares human environments and access to sophisticated healthcare, domestic dogs have unique potential to inform our understanding of the determinants of aging. Here we outline key concepts in the study of aging and illustrate the value of research with dogs, which can improve dog health and support translational discoveries. We consider similarities and differences in aging and age-related diseases in dogs and humans and summarize key advances in our understanding of genetic and environmental risk factors for morbidity and mortality in dogs. We address health outcomes ranging from cancer to cognitive function and highlight emerging research opportunities from large-scale cohort studies in companion dogs. We conclude that studying aging in dogs could overcome many limitations of laboratory models, most notably, the ability to assess how aging-associated pathways influence aging in real-world environments similar to those experienced by humans. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Accumulating Knowledge in the Organizational Sciences

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Frank A. Bosco
Keyword(s):  
Organizational Behavior ◽  
Cognitive Neuroscience ◽  
Large Scale ◽  
Scientific Progress ◽  
Science Research ◽  
Annual Review ◽  
Publication Date ◽  
Organizational Research ◽  
Research Findings ◽  
Meta Analyses

In some fields, research findings are rigorously curated in a common language and made available to enable future use and large-scale, robust insights. Organizational researchers have begun such efforts [e.g., metaBUS ( http://metabus.org/ )] but are far from the efficient, comprehensive curation seen in areas such as cognitive neuroscience or genetics. This review provides a sample of insights from research curation efforts in organizational research, psychology, and beyond—insights not possible by even large-scale, substantive meta-analyses. Efforts are classified as either science-of-science research or large-scale, substantive research. The various methods used for information extraction (e.g., from PDF files) and classification (e.g., using consensus ontologies) is reviewed. The review concludes with a series of recommendations for developing and leveraging the available corpus of organizational research to speed scientific progress. Expected final online publication date for the Annual Review of Organizational Psychology and Organizational Behavior, Volume 9 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Basis of Navigation Across Species

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Cody A. Freas ◽  
Ken Cheng
Keyword(s):  
Large Scale ◽  
Error Reduction ◽  
Annual Review ◽  
Publication Date ◽  
Additional Component ◽  
Oscillatory Systems ◽  
Neural Architecture ◽  
Wide Range ◽  
Reduction Strategies ◽  
Cycling Behavior

Animals navigate a wide range of distances, from a few millimeters to globe-spanning journeys of thousands of kilometers. Despite this array of navigational challenges, similar principles underlie these behaviors across species. Here, we focus on the navigational strategies and supporting mechanisms in four well-known systems: the large-scale migratory behaviors of sea turtles and lepidopterans as well as navigation on a smaller scale by rats and solitarily foraging ants. In lepidopterans, rats, and ants we also discuss the current understanding of the neural architecture which supports navigation. The orientation and navigational behaviors of these animals are defined in terms of behavioral error-reduction strategies reliant on multiple goal-directed servomechanisms. We conclude by proposing to incorporate an additional component into this system: the observation that servomechanisms operate on oscillatory systems of cycling behavior. These oscillators and servomechanisms comprise the basis for directed orientation and navigational behaviors. Expected final online publication date for the Annual Review of Psychology, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Variable-Temperature Native Mass Spectrometry for Studies of Protein Folding, Stabilities, Assembly, and Molecular Interactions

2021 ◽  
Vol 51 (1) ◽  
Author(s):  
Arthur Laganowsky ◽  
David E. Clemmer ◽  
David H. Russell
Keyword(s):  
Mass Spectrometry ◽  
Dynamic Range ◽  
Protein Complexes ◽  
Noncovalent Interactions ◽  
Variable Temperature ◽  
Regulatory Protein ◽  
Conformational Dynamics ◽  
Native Mass Spectrometry ◽  
Annual Review ◽  
Publication Date

The structures and conformational dynamics of proteins, protein complexes, and their noncovalent interactions with other molecules are controlled specifically by the Gibbs free energy (entropy and enthalpy) of the system. For some organisms, temperature is highly regulated, but the majority of biophysical studies are carried out at room, nonphysiological temperature. In this review, we describe variable-temperature electrospray ionization (vT-ESI) mass spectrometry (MS)-based studies with unparalleled sensitivity, dynamic range, and selectivity for studies of both cold- and heat-induced chemical processes. Such studies provide direct determinations of stabilities, reactivities, and thermodynamic measurements for native and non-native structures of proteins and protein complexes and for protein–ligand interactions. Highlighted in this review are vT-ESI-MS studies that reveal 40 different conformers of chymotrypsin inhibitor 2, a classic two-state (native → unfolded) unfolder, and thermochemistry for a model membrane protein system binding lipid and its regulatory protein. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lihe Chen ◽  
Hyun Jun Jung ◽  
Arnab Datta ◽  
Euijung Park ◽  
Brian G. Poll ◽  
...  
Keyword(s):  
Systems Biology ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Peptide Hormone ◽  
Annual Review ◽  
Publication Date ◽  
Large Scale Data ◽  
V2 Receptor ◽  
Scale Data

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing–based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailed framework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Adaptive nanopores: A bioinspired label-free approach for protein sequencing and identification

Nano Research ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 328-333 ◽  
Author(s):  
Andrea Spitaleri ◽  
Denis Garoli ◽  
Moritz Schütte ◽  
Hans Lehrach ◽  
Walter Rocchia ◽  
...  
Keyword(s):  
Amino Acids ◽  
Single Molecule ◽  
Dynamic Range ◽  
Protein Sequencing ◽  
High Fidelity ◽  
Label Free ◽  
Therapeutic Approaches ◽  
Highly Sensitive ◽  
Dynamics Simulations ◽  
Structure Of Proteins

AbstractSingle molecule protein sequencing would tremendously impact in proteomics and human biology and it would promote the development of novel diagnostic and therapeutic approaches. However, its technological realization can only be envisioned, and huge challenges need to be overcome. Major difficulties are inherent to the structure of proteins, which are composed by several different amino-acids. Despite long standing efforts, only few complex techniques, such as Edman degradation, liquid chromatography and mass spectroscopy, make protein sequencing possible. Unfortunately, these techniques present significant limitations in terms of amount of sample required and dynamic range of measurement. It is known that proteins can distinguish closely similar molecules. Moreover, several proteins can work as biological nanopores in order to perform single molecule detection and sequencing. Unfortunately, while DNA sequencing by means of nanopores is demonstrated, very few examples of nanopores able to perform reliable protein-sequencing have been reported so far. Here, we investigate, by means of molecular dynamics simulations, how a re-engineered protein, acting as biological nanopore, can be used to recognize the sequence of a translocating peptide by sensing the “shape” of individual amino-acids. In our simulations we demonstrate that it is possible to discriminate with high fidelity, 9 different amino-acids in a short peptide translocating through the engineered construct. The method, here shown for fluorescence-based sequencing, does not require any labelling of the peptidic analyte. These results can pave the way for a new and highly sensitive method of sequencing.

scholarly journals Mechanical Frequency Tuning by Sensory Hair Cells, the Receptors and Amplifiers of the Inner Ear

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Pascal Martin ◽  
A.J. Hudspeth
Keyword(s):  
Hopf Bifurcation ◽  
Hair Cells ◽  
Force Feedback ◽  
Dynamic Range ◽  
Frequency Tuning ◽  
Hair Bundle ◽  
Annual Review ◽  
Publication Date ◽  
Mechanical Waves ◽  
Myosin Motors

We recognize sounds by analyzing their frequency content. Different frequency components evoke distinct mechanical waves that each travel within the hearing organ, or cochlea, to a frequency-specific place. These signals are detected by hair cells, the ear's sensory receptors, in response to vibrations of mechanically sensitive antennas termed hair bundles. An active process enhances the sensitivity, sharpens the frequency tuning, and broadens the dynamic range of hair cells through several mechanisms, including active hair-bundle motility. A dynamic interplay between negative stiffness mediated by ion channels’ gating forces and delayed force feedback owing to myosin motors and channel reclosure by calcium ions brings the hair bundle to the vicinity of an oscillatory instability—a Hopf bifurcation. Operation near a Hopf bifurcation provides nonlinear generic features that are characteristic of hearing. Multiple gradients at molecular, cellular, and supercellular scales tune hair cells to characteristic frequencies that cover our auditory range. Expected final online publication date for the Annual Review of Condensed Matter Physics, Volume 12 is March 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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