Neurogenetics: advancing the "next-generation" of brain research

There can be little doubt that genetics has transformed our understanding of mechanisms mediating brain disorders. The last two decades have brought tremendous progress in terms of accurate molecular diagnoses and knowledge of the genes and pathways that are involved in a large number of neurological and psychiatric disorders. Likewise, new methods and analytical approaches, including genome array studies and "next-generation" sequencing technologies, are bringing us deeper insights into the subtle complexities of the genetic architecture that determines our risks for these disorders. As we now seek to translate these discoveries back to clinical applications, a major challenge for the field will be in bridging the gap between genes and biology. In this Overview of Neuron's special review issue on neurogenetics, we reflect on progress made over the last two decades and highlight the challenges as well as the exciting opportunities for the future.     

Unresolved mysteries in the biogenesis of mitochondrial membrane proteins

Mitochondria are essential eukaryotic organelles that are surrounded by two membranes. Both membranes contain a variety of different integral membrane proteins. After three decades of research on mitochondrial biogenesis five major import complexes with more than 40 subunits altogether were identified and characterized. In the current contribution we want to draw attention to some unexplored issues regarding the integration of mitochondrial membrane proteins and to formulate crucial questions that remain unanswered. This article is part of a Special Issue entitled: Protein Folding in Membranes.     

数量遗传学理论框架下的进化生态学研究：以动物模型的运用为例

目前,生态学家越来越关注深入的生物学问题,例如,1)理解生态和进化过程的互作和关系;2)种群中一个重要的表型特征,受遗传基因影响多大?即其可遗传程度,表示该性状的进化潜能;3)基因是怎样影响表型性状,及其对应的个体适合度以及种群动态?4)决定多个重要表型性状的基因之间关系和互作如何?随着生物统计软件尤其是线性混合模型的发展,结合经典数量遗传学的理论,发展出了针对上述问题的动物模型(Animal Model),使得我们可以对野外种群进行上述研究。本文首先介绍了经典数量遗传学的重要概念,随后在其理论框架下,举例介绍了动物模型的操作和使用,最后探讨和展望了利用数量遗传学方法进行进化生态学研究的前景。     

An "enactive" approach to integrative and comparative biology: thoughts on the table

We discuss the concept of Enaction as originally proposed by Varela. We attempt to exemplify through two specific topics, sensory ecology and behavior, as well as physiological and behavioral ecology, on which the enactive approach is based. We argue that sensory physiology allows us to explore the biological and cognitive meaning of animal 'private' sensory channels, beyond the scope of our own sensory capacity. Furthermore, after analyzing the interplay between factors that may impose limits upon an animal's use of time and energy, we call for a program of research in integrative and comparative biology that simultaneously considers evolutionary ecology (including physiological and behavioral ecology) and neurobiology (including cognitive mechanisms as well structural design). We believe that this approach represents a shift in scientific attitude among biologists concerning the place of biological and ecological topics in studies of integrative and comparative biology and biological diversity and vice versa.     

Multi-OMICS: a critical technical perspective on integrative lipidomics approaches

During the past decades, high-throughput approaches for analyzing different molecular classes such as nucleic acids, proteins, metabolites, and lipids have grown rapidly. These approaches became powerful tools for getting a fundamental understanding of biological systems. Considering each approach and its results separately, relations and causal connections between these classes have no chance to be revealed, since only separate molecular snapshots are provided. Only a combined approach, not fully established yet, with the integration of the corresponding data, might yield a comprehensive and complete understanding of biological processes, such as crosstalk and interactions in signaling pathways. Taking two or more omics-methods into consideration for analysis is referred to as a multi-omics approach, which is gradually evolving. In this critical note, we briefly discuss the relevance, challenges, current state, and potential of data integration from multi-omics approaches, with a special focus on lipidomics analysis, listing the advantages and gaps in this field. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.     

Plant secretome — From cellular process to biological activity

Recent studies suggest that plants secrete a large number of proteins and peptides into the extracellular space. Secreted proteins play a crucial role in stress response, communication and development of organisms. Here we review the current knowledge of the secretome of more than ten plant species, studied in natural conditions or during (a)biotic stress. This review not only deals with the classical secretory route via endoplasmic reticulum and Golgi followed by proteins containing a known N-terminal signal peptide, but also covers new findings about unconventional secretion of leaderless proteins. We describe alternative secretion pathways and the involved compartments like the recently discovered EXPO. The well characterized secreted peptides that function as ligands of receptor proteins exemplify the biological significance and activity of the secretome. This article is part of a Special Issue entitled: An Updated Secretome.     

Pollen as the link between floral phenotype and fitness

Pollen plays a key role in plant reproductive biology. Despite the long history of research on pollen and pollination, recent advances in pollen-tracking methods and statistical approaches to linking plant phenotype, pollination performance, and reproductive fitness yield a steady flow of exciting new insights. In this introduction to the Special Issue “Pollen as the Link Between Phenotype and Fitness,” we start by describing a general conceptual model linking functional classes of floral phenotypic traits to pollination-related performance metrics and reproductive fitness. We use this model as a framework for synthesizing the relevant literature, highlighting the studies included in the Special Issue, and identifying gaps in our understanding and opportunities for further development of the field. The papers that follow in this Special Issue provide new insights into the relationships between pollen production, presentation, flower morphology, and pollination performance (e.g., pollen deposition onto stigmas), the role of pollinators in pollen transfer, and the consequences of heterospecific pollen deposition. Several of the studies demonstrate exciting experimental and analytical approaches that should pave the way for continued work addressing the intriguing role of pollen in linking plant phenotypes to reproductive fitness.     

Biological insights from hydrogen exchange mass spectrometry

Over the past two decades, hydrogen exchange mass spectrometry (HXMS) has achieved the status of a widespread and routine approach in the structural biology toolbox. The ability of hydrogen exchange to detect a range of protein dynamics coupled with the accessibility of mass spectrometry to mixtures and large complexes at low concentrations result in an unmatched tool for investigating proteins challenging to many other structural techniques. Recent advances in methodology and data analysis are helping HXMS deliver on its potential to uncover the connection between conformation, dynamics and the biological function of proteins and complexes. This review provides a brief overview of the HXMS method and focuses on four recent reports to highlight applications that monitor structure and dynamics of proteins and complexes, track protein folding, and map the thermodynamics and kinetics of protein unfolding at equilibrium. These case studies illustrate typical data, analysis and results for each application and demonstrate a range of biological systems for which the interpretation of HXMS in terms of structure and conformational parameters provides unique insights into function. This article is part of a Special Issue entitled: Mass spectrometry in structural biology.     

Lipidomics: Prospects from a technological perspective

Over the last two decades, lipidomics has evolved into an ‘omics’ technology pari passu with benchmarking ‘omics’ technologies, such as genomics or proteomics. The driving force behind this development was a constant advance in mass spectrometry and related technologies. The aim of this opinion article is to give the interested reader a concise but still comprehensive overview about the technological state of the art in lipidomics, current challenges and perspectives for future development. As such, this article guides through the whole workflow of lipidomics, from sampling to data analysis. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.     

Mass spectrometry in the biology of RNA and its modifications

Many powerful analytical techniques for investigation of nucleic acids exist in the average modern molecular biology lab. The current review will focus on questions in RNA biology that have been answered by the use of mass spectrometry, which means that new biological information is the purpose and outcome of most of the studies we refer to. The review begins with a brief account of the subject "MS in the biology of RNA" and an overview of the prevalent RNA modifications identified to date. Fundamental considerations about mass spectrometric analysis of RNA are presented with the aim of detailing the analytical possibilities and challenges relating to the unique chemical nature of nucleic acids. The main biological topics covered are RNA modifications and the enzymes that perform the modifications. Modifications of RNA are essential in biology, and it is a field where mass spectrometry clearly adds knowledge of biological importance compared to traditional methods used in nucleic acid research. The biological applications are divided into analyses exclusively performed at the building block (mainly nucleoside) level and investigations involving mass spectrometry at the oligonucleotide level. We conclude the review discussing aspects of RNA identification and quantifications, which are upcoming fields for MS in RNA research. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.     

Membrane transporter research in times of countless structures

Structural biology has advanced our understanding of membrane proteins like no other scientific discipline in the past two decades and the number of high resolution membrane transporter structures solved by X-ray crystallography has increased exponentially over this time period. Currently, single particle cryo-EM is in full swing due to a recent resolution revolution and permits for structural insights of proteins that were refractory to crystallization. It is foreseeable that multiple structures of many human transporters will be solved in the coming five years. Nevertheless, many scientifically important questions remain unanswered despite of available structures, as is illustrated in this article at the example of multidrug efflux pumps and ABC transporters. Structure-function studies likely continue to be a supporting pillar of membrane transporter research. However, there is a trend towards the “integrated structural biologist”, whose research focusses on a biological question and who closely collaborates with other research groups specialized in spectroscopy techniques or molecular dynamics simulation. Future membrane protein research requires joint efforts from specialists of various disciplines to finally work towards a molecular understanding of membrane transport in the context of the living cell. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain     

The top five "game changers" in vaccinology: toward rational and directed vaccine development

Despite the tremendous success of the classical "isolate, inactivate, and inject" approach to vaccine development, new breakthroughs in vaccine research are increasingly reliant on novel approaches that incorporate cutting edge technology and advances in innate and adaptive immunology, microbiology, virology, pathogen biology, genetics, bioinformatics, and many other disciplines in order to: (1) deepen our understanding of the key biological processes that lead to protective immunity, (2) observe vaccine responses on a global, systems level, and (3) directly apply the new knowledge gained to the development of next-generation vaccines with improved safety profiles, enhanced efficacy, and even targeted utility in select populations. Here we highlight five key components foundational to vaccinomics efforts: applied immunogenomics, next generation sequencing and other cutting-edge "omics" technologies, advanced bioinformatics and analysis techniques, and finally, systems biology applied to immune profiling and vaccine responses. We believe these "game changers" will play a critical role in moving us toward the rational and directed development of new vaccines in the 21st century.     

Microbial genome mining for accelerated natural products discovery: is a renaissance in the making?

Microbial genome mining is a rapidly developing approach to discover new and novel secondary metabolites for drug discovery. Many advances have been made in the past decade to facilitate genome mining, and these are reviewed in this Special Issue of the Journal of Industrial Microbiology and Biotechnology. In this Introductory Review, we discuss the concept of genome mining and why it is important for the revitalization of natural product discovery; what microbes show the most promise for focused genome mining; how microbial genomes can be mined; how genome mining can be leveraged with other technologies; how progress on genome mining can be accelerated; and who should fund future progress in this promising field. We direct interested readers to more focused reviews on the individual topics in this Special Issue for more detailed summaries on the current state-of-the-art.     

Dynamic pattern generation in cell membranes: Current insights into membrane organization

It has been two decades since the lipid raft hypothesis was first presented. Even today, whether these nanoscale cholesterol-rich domains are present in cell membranes is not completely resolved. However, especially in the last few years, a rich body of literature has demonstrated both the presence and the importance of non-random distribution of biomolecules on the membrane, which is the focus of this review. These new developments have pushed the experimental limits of detection and have brought us closer to observing lipid domains in the plasma membrane of live cells. Characterization of biomolecules associated with lipid rafts has revealed a deep connection between biological regulation and function and membrane compositional heterogeneities. Finally, tantalizing new developments in the field have demonstrated that lipid domains might not just be associated with the plasma membrane of eukaryotes but could potentially be a ubiquitous membrane-organizing principle in several other biological systems. This article is part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo.     

Roles of helicases in translation initiation: A mechanistic view

The goal of this review is to summarize our current knowledge about the helicases involved in translation initiation and their roles in both general and mRNA-specific translation. The main topics covered are the mechanisms of helicase action, with emphasis on the roles of accessory domains and proteins; the functions performed by helicases in translation initiation; and the interplay between direct and indirect effects of helicases that also function in steps preceding translation initiation. Special attention is given to the dynamics of eIF4A binding and dissociation from eIF4F during mRNA unwinding. It is proposed that DHX29, as well as other helicases and translation initiation factors could also cycle on and off the translation initiation complexes, similar to eIF4A. The evidence in favor of this hypothesis and its possible implications for the mechanisms of translation initiation is discussed. This article is part of a Special Issue entitled: The biology of RNA helicases — Modulation for life.     

Carotenoid research: History and new perspectives for chemistry in biological systems

The history of carotenoid research as this progressed from chemistry to biochemistry and biology is outlined. Proposed roles of carotenoids in eye health, as antioxidants, and in protection against cancer and other degenerative diseases, as well as stimulatory effects on the immune system and metabolism are covered. Proposed biological actions must be consistent with the chemistry of carotenoids in the largely aqueous biological systems, which may differ from the known chemistry of carotenoids in organic solvents. In particular, carotenoids tend to form aggregates. The effects of this aggregation and of other molecular interactions in vivo are likely to be crucial to biological activity. These perspectives of the chemistry of carotenoids and carotenoid free radicals are examined and the need for carotenoid samples used in experimental work to be pure and free from breakdown products and pro-oxidant peroxides is emphasised.This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.