Project description:The goal of our study was to track changes in student understanding of the central dogma of molecular biology before and after taking a genetics course. Concept maps require the ability to synthesize new information into existing knowledge frameworks, and so the hypothesis guiding this study was that student performance on concept maps reveals specific central dogma misconceptions gained, lost, and retained by students. Students in a genetics course completed pre- and posttest concept mapping tasks using terms related to the central dogma. Student maps increased in complexity and validity, indicating learning gains in both content and complexity of understanding. Changes in each of the 351 possible connections in the mapping task were tracked for each student. Our students did not retain much about the central dogma from their introductory biology courses, but they did move to more advanced levels of understanding by the end of the genetics course. The information they retained from their introductory courses focused on structural components (e.g., protein is made of amino acids) and not on overall mechanistic components (e.g., DNA comes before RNA, the ribosome makes protein). Students made the greatest gains in connections related to transcription, and they resolved the most prior misconceptions about translation. These concept-mapping tasks revealed that students are able to correct prior misconceptions about the central dogma during an intermediate-level genetics course. From these results, educators can design new classroom interventions to target those aspects of this foundational principle with which students have the most trouble.

| S-EPMC5134937 | biostudies-literature

Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology.

Project description:The past decade has yielded much success in the identification of risk genes for Autism Spectrum Disorder (ASD), with many studies implicating loss-of-function (LoF) mutations within these genes. Despite this, no significant clinical advances have been made so far in the development of therapeutics for ASD. Given the role of LoF mutations in ASD etiology, many of the therapeutics in development are designed to rescue the haploinsufficient effect of genes at the transcriptional, translational, and protein levels. This review will discuss the various therapeutic techniques being developed from each level of the central dogma with examples including: CRISPR activation (CRISPRa) and gene replacement at the DNA level, antisense oligonucleotides (ASOs) at the mRNA level, and small-molecule drugs at the protein level, followed by a review of current delivery methods for these therapeutics. Since central nervous system (CNS) penetrance is of utmost importance for ASD therapeutics, it is especially necessary to evaluate delivery methods that have higher efficiency in crossing the blood-brain barrier (BBB).

| S-EPMC9931756 | biostudies-literature

A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

Project description:It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

| S-EPMC5739447 | biostudies-literature

Individualized VDJ recombination predisposes the available Ig sequence space.

Project description:The process of recombination between variable (V), diversity (D), and joining (J) immunoglobulin (Ig) gene segments determines an individual's naive Ig repertoire and, consequently, (auto)antigen recognition. VDJ recombination follows probabilistic rules that can be modeled statistically. So far, it remains unknown whether VDJ recombination rules differ between individuals. If these rules differed, identical (auto)antigen-specific Ig sequences would be generated with individual-specific probabilities, signifying that the available Ig sequence space is individual specific. We devised a sensitivity-tested distance measure that enables inter-individual comparison of VDJ recombination models. We discovered, accounting for several sources of noise as well as allelic variation in Ig sequencing data, that not only unrelated individuals but also human monozygotic twins and even inbred mice possess statistically distinguishable immunoglobulin recombination models. This suggests that, in addition to genetic, there is also nongenetic modulation of VDJ recombination. We demonstrate that population-wide individualized VDJ recombination can result in orders of magnitude of difference in the probability to generate (auto)antigen-specific Ig sequences. Our findings have implications for immune receptor-based individualized medicine approaches relevant to vaccination, infection, and autoimmunity.

| S-EPMC8647828 | biostudies-literature

From Gene to Function: A Safe Laboratory Exercise Promoting the Learning of the Central Dogma of Biology for the Undergraduate Biology Curriculum.

Project description: Not available

| S-EPMC7452718 | biostudies-literature

Deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B-cell development.

Project description:Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B-cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B-cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the Ig heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3?/- bone marrow. For Hdac3?/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment use. Although transcriptional effects within these loci were modest, Hdac3?/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Reintroduction of wild-type Hdac3 restored normal B-cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells.

| S-EPMC5559004 | biostudies-literature

Nucleotide Manipulatives to Illustrate the Central Dogma.

Project description: Not available

| S-EPMC4690576 | biostudies-literature

COVID-19 and the Central Dogma: an Activity To Improve Student Learning and Engagement.

Project description: Not available

| S-EPMC7669286 | biostudies-literature

Revisiting the central dogma one molecule at a time.

Project description:The faithful relay and timely expression of genetic information depend on specialized molecular machines, many of which function as nucleic acid translocases. The emergence over the last decade of single-molecule fluorescence detection and manipulation techniques with nm and Å resolution and their application to the study of nucleic acid translocases are painting an increasingly sharp picture of the inner workings of these machines, the dynamics and coordination of their moving parts, their thermodynamic efficiency, and the nature of their transient intermediates. Here we present an overview of the main results arrived at by the application of single-molecule methods to the study of the main machines of the central dogma.

| S-EPMC3063003 | biostudies-literature

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