bioRxiv Science⌕ Search

SEARCH · bioRxiv Science

Results for “molecular biology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

Multi-omic Environmental Monitoring Reveals When Molecular Signals Reflect Living Biology

Environmental molecular monitoring has transformed biodiversity detection, yet most methods capture only species presence through amplified DNA fragments, missing the biological information encoded in native nucleic acids. Here we show that a single shotgun Oxford Nanopore sequencing library from water can be read through several independent biological lenses, and that each class of molecule (environmental RNA, CpG methylation, and bulk DNA) differs in its environmental persistence, which sets the window over which signal can be trusted. Sampling Pacific salmon spawning runs, we simultaneously recovered environmental RNA indicating fresh biological input, CpG methylation profiles reflecting age demographics, and pathogen signatures reflecting health. Environmental RNA tracked spawning phenology, qPCR corroborated the timing of fresh biological input over the weeks sampled, and methylation-based age inference held only while fresh DNA dominated, a condition we term the 'Freshness Gate.' Because environmental water is not a tissue sample, we detect functional transcripts as evidence of biological input but do not infer differential gene expression, and we read methylation state but do not infer biological age outside the Freshness Gate. Variance partitioning is consistent with biological freshness, rather than technical factors such as fragment length or sequencing depth, structuring environmental methylation, though these comparisons did not reach significance at nine time points. Comparable dynamics were observed in Chinook salmon, with timing offsets following their distinct spawning season. By defining when environmental molecules faithfully encode living biology and when degradation decouples signal from current state, our framework sets practical and theoretical boundaries for multi-omic environmental monitoring.

ecology↗

Enabling AI in Synthetic Biology through Construction File Specification

The Construction File (CF) specification establishes a standardized interface for molecular biology operations, laying a foundation for automation and enhanced efficiency in experiment design. It is implemented across three distinct software projects: PyDNA_CF_Simulator, a Python project featuring a ChatGPT plugin for interactive parsing and simulating experiments; ConstructionFileSimulator, a field-tested Java project that showcases Experiment objects expressed as flat files; and C6-Tools, a JavaScript project integrated with Google Sheets via Apps Script, providing a user-friendly interface for authoring and simulation of CF. The CF specification not only standardizes and modularizes molecular biology operations but also promotes collaboration, automation, and reuse, significantly reducing potential errors. The potential integration of CF with artificial intelligence, particularly GPT-4, suggests innovative automation strategies for synthetic biology. While challenges such as token limits, data storage, and biosecurity remain, proposed solutions promise a way forward in harnessing AI for experiment design. This shift from human-driven design to AI-assisted workflows, steered by high-level objectives, charts a potential future path in synthetic biology, envisioning an environment where complexities are managed more effectively.

synthetic biology↗

Sketchy understandings: Drawings reveal where students may need additional support to understand scale and abstraction in common representations of DNA

Visual representations in molecular biology tend to follow a set of shared conventions for using certain shapes and symbols to convey information about the size and structure of nucleotides, genes, and chromosomes. Understanding how and why biologists use these conventions to represent DNA is a key part of visual literacy in molecular biology. Visual literacy, which is the ability to read and interpret visual representations, encompasses a set of skills that are necessary for biologists to effectively use models to communicate about molecular structures that cannot be directly observed. To gauge students visual literacy skills, we conducted semi-structured interviews with undergraduate students who had completed at least a year of biology courses. We asked students to draw and interpret figures of nucleotides, genes, and chromosomes, and we analyzed their drawings for adherence to conventions for representing scale and abstraction. We found that 77% of students made errors in representing scale and 86% of students made errors in representing abstraction. We also observed about half of the students in our sample using the conventional shapes and symbols to represent DNA in unconventional ways. These unconventional sketches may signal an incomplete understanding of the structure and function of DNA. Our findings indicate that students may need additional instructional support to interpret the conventions in common representations of DNA. We highlight opportunities for instructors to scaffold visual literacy skills into their teaching to help students better understand visual conventions for representing scale and abstraction in molecular biology.

scientific communication and education↗

Multiplex genome editing for synthetic biology in Vibrio natriegens

Vibrio natriegens has recently emerged as an alternative to Escherichia coli for molecular biology and biotechnology, but low-efficiency genetic tools hamper its development. Here, we uncover how to induce natural competence in V. natriegens and describe methods for multiplex genome editing by natural transformation (MuGENT). MuGENT promotes integration of large genome edits at high-efficiency on unprecedented timescales, which will extend the utility of this species for diverse applications.\n\nV. natriegens is the fastest growing organism known, with a doubling time of <10 min1,2. With broad metabolic capabilities, lack of pathogenicity, and its rapid growth rate, it is an attractive alternative to E. coli for diverse molecular biology and biotechnology applications3. Methods for classical genetic techniques have been developed for V. natriegens, but these are rel ...

synthetic biology↗

PyRID: A Brownian dynamics simulator for reacting and interacting particles written in Python

Recent technological developments in molecular biology led to large data sets providing new insights into the molecular organisation of cells. To fully exploit their potential, these developments have to be complemented by computer simulations that allow to gain in-depth understanding on molecular principles. We developed the Python-based, reaction-diffusion simulator PyRID, integrating many features for the efficient simulation of molecular biological systems. Amongst others, PyRID is capable of simulating unimolecular and bimolecular reactions as well as pair-interactions to assess the dynamics resulting from individual interacting proteins to polydisperse substrates consisting of many different molecules. Furthermore, PyRID supports mesh-based compartments and surface diffusion of particles, enabling analyses of the interaction between (trans-)membrane proteins with intra- and extracellular proteins. PyRID is written entirely in Python, which is a programming language being known for its readability and easy accessibility, such that the scientific community can easily extend PyRID to its current and future needs.

neuroscience↗

PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state.

Extracellular vesicles (EV) are comprised of vesicles budding from cell membranes and smaller intracellular vesicles shed by cells. EV play a role in remodeling the tumor microenvironment (TME) and support tumor progression. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with a carboxypeptidase function, frequently associated with poor clinical prognosis in prostate cancer (PCa). We previously identified an oncogenic PSMA signaling function in prostate cancer. Others demonstrated that EV isolated from the plasma of patients with high-grade PCa carry PSMA, but so far no pathophysiological effect has been associated with PSMA-bearing EV. Here we demonstrate that EV from PCa cells are able to transfer PSMA and its functionality to cells in the TME. The consequence of that EV-mediated PSMA transfer is an acute to long-term increased secretion of vascular endothelial growth factor-A (VEGF-A), angiogenin, pro-angiogenic and pro-lymphangiogenic mediators and increased 4E binding protein 1 (4EBP-1) phosphorylation in tumors. We compare EV from PCa cells with or without PSMA expression to address the role of PSMA-bearing EV in promoting pro-tumoral changes in the TME using classical molecular biology and novel molecular imaging approaches.

cancer biology↗

Thermal optimized PCR coupled to CRISPR-Cas12a for rapid detection of blaOXA-1 resistance gene

The {beta}-lactams are critically important broad-spectrum antibiotics, widely used as first-line treatments; however, their effectiveness is increasingly compromised by {beta}-lactamase enzymes. Among these, OXA-type enzymes have expanded to over 400 variants and are highly prevalent in Enterobacteriaceae. Current phenotypic and molecular detection tests have long turnaround times or require specialized equipment, respectively. In this study, we optimize a rapid molecular assay combining a PCR with modified thermal ramp rate (TRR) along with CRISPR-Cas12a fluorescence detection for the blaOXA-1gene. Using a commercial DNA Taq polymerase (TRR: 2.2 {degrees}C/s, annealing and extension hold time: 1 s), amplification time was reduced from 80 to 30 min, enabling detection within 50 min (PCR: 30 min; CRISPR: 20 min). With a locally produced enzyme (hold: 10 s), amplification time was 44 min. The assay achieved an analytical sensitivity of 8 CFU/reaction using commercial DNA Taq polymerase. The accelerated PCR:CRISPR workflow delivers results in less than one hour without compromising technical sensitivity (attomoles range), not requiring high technical expertise, and can be implemented in laboratories with basic molecular biology equipment. HighlightsAn optimized thermal gradient can reduce the turnaround time of PCR-based detection tests CRISPR-Cas in addition to the modified PCR can detect a gene target in less than an hour The proposed workflow is suitable for implementation with basic molecular biology equipment

molecular biology↗

Homeostatic Controllers Compensating for Growth and Perturbations

Cells and organisms have developed homeostatic mechanisms to maintain internal stabilities which protect them against a changing environment. How cellular growth and homeostasis interact is still not well understood, but of increasing interest to the synthetic and molecular biology community where molecular control circuits are sought and tried to maintain homeostasis that opposes the diluting effects of cell growth. In this paper we describe the performance of four negative feedback (inflow) controllers, which, for different observed growth laws (time-dependent increase in the cellular volume V) are able to compensate for various time-dependent removals of the controlled variable A. The four implementations of integral control are based on zero-order, first-order autocatalytic, second-order (antithetic), and derepressing inhibition kinetics. All controllers behave ideal in the sense that they for step-wise perturbations in V and A are able to drive the controlled variable precisely back to the controllers theoretical set-point [Formula] The applied increase in cellular volume includes linear, exponential and saturating growth and reflect experimentally observed growth laws of single cell organisms and other cell types. During the increase in V, additional linear or exponential time-dependent perturbations which remove A are applied, and controllers are tested with respect to their ability to compensate for both the increase in volume V and the applied perturbations removing A. Our results show that the way how integral control is kinetically implemented and the structure of the negative feedback loop are essential determinants of a controllers performance. The results provide a ranking between the four tested controller types. Considering exponential volume increases together with an exponentially increasing removal rate of A controllers based on derepression kinetics perform best, but break down when the control-inhibitors concentration gets too low. The first-order autocatalytic controller is able to defend time-dependent exponential growth and removals in A, but generally with a certain offset below its theoretical set-point [Formula] The controllers based on zero-order and second-order (antithetic) integral feedback can only manage linear increases in V and removals in A, in dependence of the controllers aggressiveness. Our results provide a theoretical basis what controller kinetics are needed in order to compensate for different growth laws.

biophysics↗

GEMOT: Towards Mechanistic World Models for Biology

Scientific discovery seeks mechanisms that explain observations and predict beyond the measurements that produced them. Whereas large language models (LLMs) encode knowledge implicitly, mechanistic world models organise it as a parsimonious set of explicit, modular, reusable mechanisms whose predictions can be scored against data. In biology, where measurements are sparse and noisy, mechanistic world modelling must discover latent states and governing equations jointly, yet the prior knowledge that could constrain this search is largely unstructured. We introduce gemot, an agentic framework for mechanistic world modelling, and evaluate it on 18 published biological problems spanning molecular biology, epidemiology, and immune-cell differentiation, with up to 1,755 training measurements, 65 observables, 170 experimental conditions, and 3 data modalities per problem. gemot is auditable by construction: a semantic layer records each hypothesis, and a Model Context Protocol layer separates hypothesis formulation from numerical evaluation, so hypothesis scoring cannot be fabricated. On every problem, autonomously constructed models match or exceed the reference models in fit and parsimony, and generalise where held-outs exist. We demonstrate that gemot can formulate novel, biologically plausible mechanistic hypotheses. This work will enable decoding of interventional biological data into competing mechanistic hypotheses and design experiments that distinguish between them, and may serve as a blueprint for mechanistic world modelling in other domains.

systems biology↗

A systems biology-based molecular model of the protein kinase C life cycle

Protein kinase C (PKC) enzymes are a family of kinases that mediate signal transduction originating at the cell surface. Most cell membranes can contain functional PKC enzymes. Aberrations in the PKC life cycle may result cellular damage and dysfunction. For example, some cancerous cells exhibit alterations in PKC activity. Here, we use a systems biology approach to describe a molecular model of the PKC life cycle. Understanding the PKC life cycle is necessary to identify new anticancer drug targets. The PKC life cycle is composed of three key regulatory processes: maturation, activation and termination. These processes precisely control PKC enzyme levels. This model describes the fate of PKC during de novo synthesis and PKCs lipid-mediated activation cycle. We utilize a systems biology approach to show the PKC life cycle is controlled by multiple phosphorylation and dephosphorylation events. PKC processing events can be divided into two types: maturation via processing of newly synthesized enzyme and secondary messenger-dependent activation of dormant, but catalytically-competent enzyme. Newly synthesized PKC enzyme is constitutively processed through three ordered phosphorylations and stored in the cytosol as a stable, signaling-competent inactive and autoinhibited molecule. Upon extracellular stimulation, diacylglycerol (DAG) and calcium ion (Ca+2) generated at the membrane bind PKC. PKC then undergoes cytosol-to-membrane translocation and subsequent activation. Our model shows that, once activated, PKC is prone to dephosphorylation and subsequent degradation. This model also describes the role of HSP70 in stabilization and re-phosphorylation of dephosphorylated PKC, replenishing the PKC pool. Our model shows how the PKC pool responds to different intensities of extracellular stimuli? We show that blocking PHLPP dephosphorylation replenishes the PKC pool in a dose-dependent manner. This model provides a comprehensive understanding of PKC life cycle regulation.

systems biology↗

Autonomous Remotely Controlled Closed System Transgenic Cell Technologies Robot: CRISPR.BOT

In manually advancing experimental processes, the stages may be long-term and need to be repeated. Human errors with the repetition of the steps turn into a time-consuming and high-cost for the experiment processes. For this reason, autonomous liquid processing systems are promising technologies. However, in addition to the high cost of fully automatic systems, their maintenance is also quite expensive. Furthermore, conventional systems usually require system-specific protocols and laboratory equipment. Here, we aimed to show that the autonomous robotic systems may provide a closed and error-free molecular biology bench to perform genetic engineering automatically, quickly, and practically 7-24. In this way, researchers can save time from repetitive experiment processes and perform BSL3 experiments including pathogens without human contact. In this study, we built CRISPR.BOT robotic systems to perform Green Fluorescent Protein (GFP) encoding plasmid DNA transfer into bacteria, lentiviral transduction of the gene-of-interests including GFP encoding gene and CRISPR-Cas9 with gRNAs genetic editing system to a human cell line. Furthermore, we showed that CRISPR.BOT system achieved to accomplish single-cell subcloning of GFP+ CRISPR-gRNA+ cells with 90-100% purity. This study suggests that CRISPR.BOT-like approaches may reduce manpower in a safely closed bench in which molecular biology and genetic engineering can be done by robots in a closed system without touching pathogenic microorganisms (virus or bacteria, for example, SARS CoV-2 virus). Furthermore, LEGO Mindstorms robots showed to have the potential to be used in daily laboratory routines with their cost-effectiveness reduced by up to 50 times compared to normal commercial robots.

molecular biology↗

Auto-qPCR: A Python based web app for automated and reproducible analysis of qPCR data

Quantifying changes in DNA and RNA levels is essential in numerous molecular biology protocols. Quantitative real time PCR (qPCR) techniques have evolved to become commonplace, however, data analysis includes many time-consuming and cumbersome steps, which can lead to mistakes and misinterpretation of data. To address these bottlenecks, we have developed an open-source Python software to automate processing of result spreadsheets from qPCR machines, employing calculations usually performed manually. Auto-qPCR is a tool that saves time when computing qPCR data, helping to ensure reproducibility of qPCR experiment analyses. Our web-based app (https://auto-q-pcr.com/) is easy to use and does not require programming knowledge or software installation. Using Auto-qPCR, we provide examples of data treatment, display and statistical analyses for four different data processing modes within one program: (1) DNA quantification to identify genomic deletion or duplication events; (2) assessment of gene expression levels using an absolute model, and relative quantification (3) with or (4) without a reference sample. Our open access Auto-qPCR software saves the time of manual data analysis and provides a more systematic workflow, minimizing the risk of errors. Our program constitutes a new tool that can be incorporated into bioinformatic and molecular biology pipelines in clinical and research labs.

molecular biology↗

The RNase and RNA binding activities of selected RNase R truncations and mutations plus a detailed step by step protocol to purify recombinant RNase R

RNase R is a processive 3 to 5 exoribonuclease that degrades a broad array of linear RNA species while preserving RNA lariats and circular RNAs (circRNA). In recent years, this enzyme has become pivotal for the field of circRNA research, serving as a key step for circRNA enrichment, purification, and identification. Despite this growing importance, the effects of mutations and truncations in RNase R have been incompletely studied. We make several point mutations and assay their effects on the ability of RNase R to bind and/or degrade RNA substrates. Our data show that selected active site mutations have varying effects on RNA binding and degradation. Furthermore, the increasing interest in circRNA-based RNA therapeutic platforms highlights an urgent need for RNase R in RNA molecular biology labs. However, the substantial cost of commercial RNase R remains a bottleneck, particularly for large-scale studies or the development of circRNA-based technologies. In this protocol, we offer a solution to that problem, namely a more accessible and cost-effective means of purifying high-quality and low-cost RNase R. We provide a highly detailed yet simplified, high-yield protocol that produces recombinant RNase R from Escherichia coli. The method uses a single-step Ni-NTA affinity chromatography procedure without proteolytic tag removal and is optimized for entry-level FPLC systems such as the AKTA Start, ensuring that high-purity enzyme production does not require specialized, high-end instrumentation. A second key feature is the establishment of an optimized reaction framework, including specific buffer compositions and defined enzyme-to-substrate ratios for the purified RNase R. The protocol achieves functional equivalence to premium commercial RNase R, ensuring complete linear RNA digestion without compromising the integrity of circRNA. The combination of a simplified purification workflow and a robust reaction protocol provides an accessible, cost-effective, and reliable solution for any molecular biology laboratory requiring high volumes of RNase R. Key FeaturesO_LIRNase R mutations can block RNase activity, RNA binding or both C_LIO_LIThis protocol purifies [~]40 mg of active RNase R per liter of E. coli culture C_LIO_LIThe protocol avoids medium and high end FPLC systems C_LIO_LIRNase R expression constructs (WT and mutants) will be available on Addgene C_LIO_LIThe protocol includes an optimized reaction buffer to pair with this RNase R C_LIO_LIOptional endotoxin removal step is also included C_LI

molecular biology↗

Estrogen Receptor Enhancers Sensitive to Low Doses of Hormone Specify Distinct Molecular and Biological Outcomes

Adult women are typically exposed to estradiol (E2) concentrations of [~]100-200 pM, yet most cell-based studies use 100 nM. We determined the molecular effects of E2 concentrations spanning six orders of magnitude (1 pM to 100 nM) in breast cancer cells. Estrogen receptor alpha (ER) enhancers formed at low physiological doses of E2 (1-100 pM) are mechanistically distinct from those that form at high pharmacological doses (10-100 nM). They (1) form in open chromatin bound by FOXA1, (2) produce enhancer RNAs enriched with functional eRNA regulatory motifs (FERMs), and (3) drive expression of cell proliferation genes with promoter-proximal paused RNA polymerase II. Importantly, low dose ER enhancer usage is elevated in breast cancer patients with poor responses to aromatase inhibitors, likely as a continued response to low circulating levels of E2. Collectively, our results identify mechanistic differences between low and high dose ER enhancers that specify distinct biological outcomes.

genomics↗

YhcB (DUF1043), a novel cell division protein conserved across gamma-proteobacteria

YhcB, an uncharacterized protein conserved across gamma-proteobacteria, is composed predominantly of a single Domain of Unknown Function (DUF 1043) with an N-terminal transmembrane -helix. Here, we show that E. coli YhcB is a conditionally essential protein that interacts with the proteins of the cell divisome (e.g., FtsI, FtsQ) and elongasome (e.g., RodZ, RodA). We found 7 interactions of YhcB that are conserved in Yersinia pestis and/or Vibrio cholerae. Furthermore, we identified several point mutations that abolished interactions of YhcB with FtsI and RodZ. The yhcB knock-out strain does not grow at 45{degrees}C and is hypersensitive to cell-wall acting antibiotics even in stationary phase. The deletion of yhcB leads to filamentation, abnormal FtsZ ring formation, and aberrant septa development. The 2.8 [A] crystal structure for the cytosolic domain from Haemophilus ducreyi YhcB shows a unique tetrameric -helical coiled-coil structure that combines parallel and anti-parallel coiled-coil intersubunit interactions. This structure is likely to organize interprotein oligomeric interactions on the inner surface of the cytoplasmic membrane, possibly involved in regulation of cell division and/or envelope biogenesis/integrity in proteobacteria. In summary, YhcB is a conserved and conditionally essential protein that is predicted to play a role in cell division and consequently or in addition affects envelope biogenesis. ImportanceOnly 0.8 % of the protein annotations in the UniProt are based on experimental evidence and thus, functional characterization of unknown proteins remains a rate-limiting step in molecular biology. Herein, the functional properties of YhcB (DUF1043) were investigated using an integrated approach combining X-ray crystallography with genetics and molecular biology. YhcB is a conserved protein that appears to be needed for the transition from exponential to stationary growth and is involved in cell division and/or envelope biogenesis/integrity. This study will serve as a starting point for future studies on this protein family and on how cells transit from exponential to stationary survival.

microbiology↗

The Macerprep: a minimalist kit- and enzyme-free high-yield miniprep utilising alkaline lysis and alkaline hydrolysis principles

The commercialisation of miniprep kits supplanted the original alkaline lysis method for plasmid DNA preparation, and had remained relatively unchanged for almost two decades. The Miraprep substantially improved the yields of miniprep kits. However, the method still relies on commercial kits, which can be a burden financially to certain projects. Additionally, Pronobis et al. also identified loss of RNAse activities in miniprep kits over time. The present novel plasmid DNA isolation protocol addresses the two issues mentioned above utilising alkaline lysis and alkaline hydrolysis principles. With a largely identical workflow and operation time, the Macerprep will significantly reduce costs of establishing new laboratories as well as maintenance of running molecular biology laboratories.

molecular biology↗

Probing visual literacy skills reveals student conceptions of scale and abstraction with respect to chromosomes

Molecular biology can be difficult for undergraduate students because course content is often taught using highly-abstract visual representations. Genetic concepts can be depicted with lines, letters, shapes, and symbols, and students need to engage their visual literacy skills to appropriately decipher these abstract representations. We previously found that undergraduate course materials almost always represent chromosomes in abstract forms, such as "X" shapes or straight lines with a dot for the centromere. We hypothesized that students struggle to apply their visual literacy skills to accurately interpret these abstract representations of chromosomes, which may be related to the frequently-documented incomplete or incorrect ideas students have about chromosome structure and function. To explore students visual literacy related to representations of chromosomes, we conducted 35 semi-structured interviews with students who had taken at least a year of biology courses. We asked them to sketch chromosomes, interpret an abstract representation of chromosomes, and use the abstract representation to answer a question about meiosis. We found that 97% of participants (34 of 35) held conceptual errors related to chromosome structure and function. These conceptual errors were often not evident in participants verbal definitions of chromosomes and were only revealed in their sketches or explanations of their sketches. We found that participants frequently misinterpreted X-shaped representations of chromosomes, mistook unreplicated homologous chromosomes as separated sister chromatids, and held misconceptions related to the structure and function of centromeres. These findings have implications for how chromosomes are taught in biology courses. We recommend that instructors explicitly discuss the conventions and norms of representing chromosomes as a pathway for increasing students visual literacy in molecular biology.

scientific communication and education↗

A simple method for mapping the location of cross-β forming regions within protein domains of low sequence complexity

Protein domains of low sequence complexity are unable to fold into stable, three-dimensional structures. In test tube studies, these unusual polypeptide regions can self-associate in a manner causing phase separation from aqueous solution. This form of protein:protein interaction has been implicated in numerous examples of dynamic morphological organization within eukaryotic cells. In several cases, the basis for low complexity domain (LCD) self-association and phase separation has been traced to the formation of labile cross-{beta} structures. The primary energetic force favoring formation of these transient and reversible structures is enabled by polypeptide backbone interactions. Short, contiguous networks of peptide backbone amino groups and carbonyl oxygens are zippered together intermolecularly by hydrogen bonding as described by Linus Pauling seven decades ago. Here we describe a simple, molecular biological method useful for the identification of localized, self-associating regions within larger protein domains of low sequence complexity. SignificanceThis study describes a molecular biological method for analyzing protein domains of low sequence complexity in search of segments that mediate self-association and consequent phase separation both in vitro and in vivo. Small regions allowing for self-association correspond to sequences that specify the formation of labile cross-{beta} structural order. When juxtaposed to the C-terminus of GFP, cross-{beta} prone regions suppress fluorescence. A tiled scan of overlapping fragments of the low complexity domain (LCD) of the TDP-43 RNA binding protein pinpointed an evolutionarily conserved sequence of twenty amino acids essential for self-association, phase separation and the formation of nuclear speckles. The screening method described herein should be useful for the analysis of any LCD believed to function via homotypic self-association.

biochemistry↗