RESUMEN

Systems biology and multiomics research expand the prospects of planetary health innovations. In this context, this mini-review unpacks the twin scholarships of glycomedicine and precision medicine in the current era of single-cell multiomics. A significant growth in glycan research has been observed over the past decade, unveiling and establishing co- and post-translational modifications as dynamic indicators of both pathological and physiological conditions. Systems biology technologies have enabled large-scale and high-throughput glycoprofiling and access to data-intensive biological repositories for global research. These advancements have established glycans as a pivotal third code of life, alongside nucleic acids and amino acids. However, challenges persist, particularly in the simultaneous analysis of the glycome and transcriptome in single cells owing to technical limitations. In addition, holistic views of the complex molecular interactions between glycomics and other omics types remain elusive. We underscore and call for a paradigm shift toward the exploration of integrative glycan platforms and analysis methods for single-cell multiomics research and precision medicine biomarker discovery. The integration of multiple datasets from various single-cell omics levels represents a crucial application of systems biology in understanding complex cellular processes and is essential for advancing the twin scholarships of glycomedicine and precision medicine.

Asunto(s)

RESUMEN

Analogies are used to make abstract topics meaningful and more easily comprehensible to learners. Incorporating simple analogies into STEM classrooms is a fairly common practice, but the analogies are typically generated and explained by the instructor for the learners. We hypothesize that challenging learners to create complex, extended analogies themselves can promote integration of content knowledge and development of critical thinking skills, which are essential for deep learning, but are challenging to teach. In this qualitative study, college biology students (n = 30) were asked to construct a complex analogy about the flow of genetic information using a familiar item. One week later, participants constructed a second analogy about the same topic, but this time using a more challenging item. Twenty participants worked on the challenging analogy in pairs, while the other 10 worked alone. Analysis of the 50 interviews resulted in a novel-scoring scheme, which measured both content knowledge (understanding of biology terms) and critical thinking (alignment of relationships between elements of the analogy). Most participants improved slightly due to practice, but they improved dramatically when working with a partner. The biggest gains were seen in critical thinking, not content knowledge. Having students construct complex, sophisticated analogies in pairs is a high-impact practice that can help students develop their critical thinking skills, which are crucial in academic and professional settings. The discussion between partners likely requires students to justify their explanations and critique their partner's explanations, which are characteristics of critical thinking.

RESUMEN

The creation of a self-replicating synthetic cell is an essential to understand life self-replication. One method to create self-replicating artificial cells is to reconstitute the self-replication system of living organisms in vitro. In a living cell, self-replication is achieved via a system called the autonomous central dogma, a system in which central dogma-related factors are autonomously synthesized and genome replication, transcription, and translation are driven by nascent factors. Various studies to reconstitute some processes of the autonomous central dogma in vitro have been conducted. However, in vitro reconstitution of the entire autonomous central dogma system is difficult as it requires balanced expression of several related genes. Therefore, we developed a method to simultaneously quantify and optimize the in vitro expression balance of multiple genes. First, we developed a quantitative mass spectrometry method targeting genome replication-related proteins as a model of central dogma-related factors and acquired in vitro expression profiles of these genes. Additionally, we demonstrated that the in vitro expression balance of these genes can be easily optimized by adjusting the input gene ratio based on the data obtained by the developed method. This study facilitated the easy optimization of the in vitro expression balance of multiple genes. Therefore, extending the scope of this method to other central dogma-related factors will accelerate attempts of self-replicating synthetic cells creation.

Asunto(s)

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has underscored the importance of mRNA vaccines. The mechanism for how such vaccines work is related to the core biology topic of the central dogma, which students often misunderstand despite its importance. Therefore, we wanted to know whether students can apply their biology knowledge of central dogma to the real-world issue of how mRNA COVID vaccines work. Accordingly, we asked college biology students of different expertise levels how the COVID vaccine worked. Later, we cued them by telling them the vaccine contains mRNA and asked them what the mRNA does. We used thematic analysis to find common ideas in their responses. In the uncued condition, fewer than half of the students used central dogma-related ideas to explain what was in the vaccine or how the vaccine worked. Inaccurate ideas were present among all groups of biology students, particularly entering biology majors and non-biology majors, including the idea that the COVID vaccines contain a weakened, dead, or variant form of the COVID virus. After students were cued, many more students in all expertise groups expressed central dogma-related themes, showing that students could apply the knowledge of central dogma if prompted. Advanced biology majors were much more likely to state that the vaccines code for a viral protein, indicating their advanced application of central dogma concepts. These results highlight inaccurate ideas common among students and show changes in the ability to apply knowledge with student expertise level, which could inform future interventions to support student learning about vaccines and central dogma.

RESUMEN

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

RESUMEN

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

RESUMEN

The translation of messenger RNA (mRNA) into proteins represents the culmination of gene expression. Recent technological advances have revolutionized our ability to investigate this process with unprecedented precision, enabling the study of translation at the single-molecule level in real time within live cells. In this review, we provide an overview of single-mRNA translation reporters. We focus on the core technology, as well as the rapid development of complementary probes, tags, and accessories that enable the visualization and quantification of a wide array of translation dynamics. We then highlight notable studies that have utilized these reporters in model systems to address key biological questions. The high spatiotemporal resolution of these studies is shedding light on previously unseen phenomena, uncovering the full heterogeneity and complexity of translational regulation.

Asunto(s)

RESUMEN

The central dogma of molecular biology is a key concept for undergraduate students in the life sciences as it describes the flow of information in living systems from gene-to-gene product. However, despite often being covered in many introductory life science courses, students may still have misconceptions surrounding the central dogma even as they move on to advanced courses. Active learning strategies such as laboratory activities can be useful in addressing such misconceptions. In the laboratory exercise presented here, senior undergraduate students explore the intricacies of nonsense suppressor mutations to challenge their understanding of the central dogma. The students introduce a plasmid carrying a nonfunctional chromogenic protein gene due to a nonsense mutation in a codon encoding the chromophore to various nonsense suppressor strains of Escherichia coli. Students then observe distinct chromogenic phenotypes, depending on the suppressor strain. Students showed a moderate increase in understanding of the central dogma. While the central dogma remains a challenging concept, active learning strategies like the one presented here can help reduce conceptual errors.

RESUMEN

Smart manufacturing needs cognitive computing methods to make the relevant systems more intelligent and autonomous. In this respect, bio-inspired cognitive computing methods (i.e., biologicalization) can play a vital role. This article is written from this perspective. In particular, this article provides a general overview of the bio-inspired computing method called DNA-Based Computing (DBC), including its theory and applications. The main theme of DBC is the central dogma of molecular biology (once information of DNA/RNA has got into a protein, it cannot get out again), i.e., DNA to RNA (sequences of four types of nucleotides) and DNA/RNA to protein (sequence of twenty types of amino acids) are allowed, but not the reverse ones. Thus, DBC transfers few-element information (DNA/RAN-like) to many-element information (protein-like). This characteristic of DBC can help to solve cognitive problems (e.g., pattern recognition). DBC can take many forms; this article elucidates two main forms, denoted as DBC-1 and DBC-2. Using arbitrary numerical examples, we demonstrate that DBC-1 can solve various cognitive problems, e.g., "similarity indexing between seemingly different but inherently identical objects" and "recognizing regions of an image separated by a complex boundary." In addition, using an arbitrary numerical example, we demonstrate that DBC-2 can solve the following cognitive problem: "pattern recognition when the relevant information is insufficient." The remarkable thing is that smart manufacturing-based systems (e.g., digital twins and big data analytics) must solve the abovementioned problems to make the manufacturing enablers (e.g., machine tools and monitoring systems) more self-reliant and autonomous. Consequently, DBC can improve the cognitive problem-solving ability of smart manufacturing-relevant systems and enrich their biologicalization.

RESUMEN

Gastrointestinal cancers account for 11.6 % of all cancers, and are the second most frequently diagnosed type of cancer worldwide. Traditional Chinese medicine (TCM), together with Western medicine or alone, has unique advantages for the prevention and treatment of cancers, including gastrointestinal cancers. Syndrome differentiation and treatment are basic characteristics of the theoretical system of TCM. TCM syndromes are the result of the differentiation of the syndrome and the basis of treatment. Genomics, transcriptomics, proteomics, metabolomics, intestinal microbiota, and serology, generated around the central law, are used to study the biological basis of TCM syndromes in gastrointestinal cancers. This review summarizes current research on the biological basis of TCM syndrome in gastrointestinal cancers and provides useful references for future research on TCM syndrome in gastrointestinal cancers.

RESUMEN

Generative artificial intelligence (AI) is a burgeoning field with widespread applications, including in science. Here, we explore two paradigms that provide insight into the capabilities and limitations of Chat Generative Pre-trained Transformer (ChatGPT): its ability to (i) define a core biological concept (the Central Dogma of molecular biology); and (ii) interpret the genetic code.

Asunto(s)

RESUMEN

The disciplinary identity of molecular biology has frequently been called into question. Although the debates might sometimes have been more about creating or debunking myths, defending intellectual territory and the distribution of resources, there are interesting underlying questions about this area of biology and how it is conceptually organized. By looking at the history of molecular biology, its origins and development, I examine the possible criteria for its status as a scientific discipline. Doing so allows us to answer the title question in such a way that offers a reasonable middle ground, where molecular biology can be properly viewed as a viable interdisciplinary program that can very well be called a discipline in its own right, even if no strict boundaries can be established. In addition to this historical analysis, a couple of systematic issues from a philosophy of science perspective allow for some assessment of the current situation and the future of molecular biology.

Asunto(s)

RESUMEN

Central dogma is the most fundamental hypothesis in the field of molecular biology and explains the genetic information flow from DNA to protein. Beyond residue-by-residue transmission of sequential information, chemical modifications of DNA, RNA, and protein are also relayed in the course of gene expression. Here, this work presents recent evidence supporting bidirectional interplay between chromatin modifications and RNA modifications. Furthermore, several RNA modifications likely affect chemical modifications of proteins. The relay of chemical modifications occurs co-transcriptionally or co-translationally, ensuring crosstalk among chemical modifications at the DNA, RNA, and protein levels. Overall, this work proposes a hypothetical framework that represents transmission of chemical modification information among chromatin, RNA, and proteins.

RESUMEN

In the past decades, various xenobiotic nucleic acids (XNAs), including 2'-modified nucleic acids, have been developed as novel genetic materials and demonstrated great potential in synthetic biology and biotechnology. Enzymatic polymerization and replication of these artificial polymers are obviously the prerequisite to make full use of them, and DNA and RNA polymerases from different families have thus been extensively engineered for these purposes. However, the performance of engineered XNA polymerases is still far from satisfactory, especially in terms of the efficiency of synthesizing XNA with bigger lengths and the capability of directly replicating XNAs or transcribing one XNA to another. In this work, we tailored a mutant of Stoffel fragment of Taq DNA polymerase, SFM4-3, by engineering a key residue pair on the surfaces of fingers and thumb domains, and successfully obtained mutants with significantly enhanced efficiency for the synthesis of fully 2'-OMe-modified DNA with bigger lengths. Remarkably, we also found that these polymerase mutants are capable of synthesizing, reverse transcribing, and even replicating RNA and different fully 2'-modified XNAs, as well as transcribing one of these nucleic acids to another, with varied efficiencies. The application of these activities for producing DNA strands end-protected by XNA duplexes was then demonstrated. These results clearly suggest that the genetic information can be stored in and transmitted among DNA, RNA, and different 2'-modified XNAs with the assistance of polymerase mutants, and the central dogma of life can be expanded to higher dimensions via the development of XNAs together with engineering their polymerases.

Asunto(s)

RESUMEN

Recent advances in in vitro synthetic biology have made it possible to reconstitute various cellular functions in a test tube. However, the integration of these functions remains a major challenge. This study aimed to identify a suitable condition to achieve all three reactions that constitute the central dogma: transcription, translation, and DNA replication. Specifically, we investigated the effect of the concentrations of 11 nonprotein factors required for in vitro transcription, translation, and DNA replication on each of these reactions. Our results indicate that certain factors have opposing effects on the three reactions. For example, while dNTP is necessary for DNA replication, it inhibited translation, and both rNTP and tRNA, which are essential for transcription and translation, inhibited DNA replication with several DNA polymerases. We also found that these opposing effects were partially alleviated by optimizing the magnesium concentration. Using this knowledge, we successfully demonstrated transcription/translation-coupled DNA replication with higher levels of transcription and translation while maintaining a certain level of DNA replication. These findings not only provide useful insights for the development of a complex artificial system with the central dogma but also raise the question of how natural cells overcome the incompatibility between the three reactions.

Asunto(s)

RESUMEN

Crick's Central Dogma has been a foundational aspect of 20th century biology, describing an implicit relationship governing the flow of information in biological systems in biomolecular terms. Accumulating scientific discoveries support the need for a revised Central Dogma to buttress evolutionary biology's still-fledgling migration from a Neodarwinian canon. A reformulated Central Dogma to meet contemporary biology is proposed: all biology is cognitive information processing. Central to this contention is the recognition that life is the self-referential state, instantiated within the cellular form. Self-referential cells act to sustain themselves and to do so, cells must be in consistent harmony with their environment. That consonance is achieved by the continuous assimilation of environmental cues and stresses as information to self-referential observers. All received cellular information must be analyzed to be deployed as cellular problem-solving to maintain homeorhetic equipoise. However, the effective implementation of information is definitively a function of orderly information management. Consequently, effective cellular problem-solving is information processing and management. The epicenter of that cellular information processing is its self-referential internal measurement. All further biological self-organization initiates from this obligate activity. As the internal measurement by cells of information is self-referential by definition, self-reference is biological self-organization, underpinning 21st century Cognition-Based Biology.

Asunto(s)

RESUMEN

How life emerged from simple non-life chemicals on the ancient Earth is one of the greatest mysteries in biology. The gene expression system of extant life is based on the interdependence between multiple molecular species (DNA, RNA, and proteins). While DNA is mainly used as genetic material and proteins as functional molecules in modern biology, RNA serves as both genetic material and enzymes (ribozymes). Thus, the evolution of life may have begun with the birth of a ribozyme that replicated itself (the RNA world hypothesis), and proteins and DNA joined later. However, the complete self-replication of ribozymes from monomeric substrates has not yet been demonstrated experimentally, due to their limited activity and stability. In contrast, peptides are more chemically stable and are considered to have existed on the ancient Earth, leading to the hypothesis of RNA-peptide co-evolution from the very beginning. Our group and collaborators recently demonstrated that (1) peptides with both hydrophobic and cationic moieties (e.g., KKVVVVVV) form ß-amyloid aggregates that adsorb RNA and enhance RNA synthesis by an artificial RNA polymerase ribozyme and (2) a simple peptide with only seven amino acid types (especially rich in valine and lysine) can fold into the ancient ß-barrel conserved in various enzymes, including the core of cellular RNA polymerases. These findings, together with recent reports from other groups, suggest that simple prebiotic peptides could have supported the ancient RNA-based replication system, gradually folded into RNA-binding proteins, and eventually evolved into complex proteins like RNA polymerase.

Asunto(s)

RESUMEN

Commentary to "The gene: An appraisal" by Keith Baverstock. PBMB, Volume 164, September 2021, Pages 46-62. NOTE: this short and informal commentary constructively criticizes the very interesting approach in the paper by a brief survey of the work that a few of us develop since several years. I will first recall the very pertinent critique of the Modern Synthesis and the genocentric approach presented in the paper, then suggest a methodological (and theoretical) critique of the approach by K. Baverstock and hint to alternatives paths that are compatible, but "extend" the physics for biology presented by the author. The purposes and the space allowed force a limited number of references and technical details. These may be found in the references contained in the few papers quoted below that are not the most nor the only representative contributions to the that work, but are inserted as a source of references or as synthetic presentations of our views.

Asunto(s)

RESUMEN

The idea of The Selfish Gene, first published in 1976, grew out of the Modern Synthesis of evolutionary biology formulated by Julian Huxley in 1942, and more specifically from George Williams' Adaptation and Natu - ral Selection in 1966. It presents a severely narrowed down version of Huxley's synthesis, which developed in the 1960s following the formulation of the Cen tral Dogma of molecular biology by Francis Crick. The idea rests on three assumptions: the isolation of the genome from any influences by the soma and its development in interaction with the environment (the Weis - mann Barrier), one-way causation from DNA to proteins (The Central Dogma), and the autoreplication of DNA (Schrödinger's aperiodic crystal). All three of these assumptions have now been shown to be incorrect. The 'replicator' (DNA) is not independent of the 'vehicle', the organism itself, so that The Selfish Gene can no longer be regarded as a valid scientific hypothesis.

Asunto(s)