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De novo design of discrete, stable 310-helix peptide assemblies

De novo design of discrete, stable 310-helix peptide assemblies | SynBioFromLeukipposInstitute | Scoop.it
The α-helix is pre-eminent in structural biology1 and widely exploited in protein folding2, design3 and engineering4. Although other helical peptide conformations do exist near to the α-helical region of conformational space—namely, 310-helices and π-helices5—these occur much less frequently in protein structures. Less favourable internal energies and reduced tendencies to pack into higher-order structures mean that 310-helices rarely exceed six residues in length in natural proteins, and that they tend not to form normal supersecondary, tertiary or quaternary interactions. Here we show that despite their absence in nature, synthetic peptide assemblies can be built from 310-helices. We report the rational design, solution-phase characterization and an X-ray crystal structure for water-soluble bundles of 310-helices with consolidated hydrophobic cores. The design uses six-residue repeats informed by analysing 310-helical conformations in known protein structures, and incorporates α-aminoisobutyric acid residues. Design iterations reveal a tipping point between α-helical and 310-helical folding, and identify features required for stabilizing assemblies of 310-helices. This work provides principles and rules to open opportunities for designing into this hitherto unexplored region of protein-structure space. A study demonstrates the rational de novo design of water-soluble assemblies constructed from long 310-helical peptides, and details their characterization by circular dichroism spectroscopy, analytical ultracentrifugation and X-ray crystallography.
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Algorithms for protein design

Computational Protein Design has the potential to contribute to major advances in enzyme technology, vaccine design, receptor-ligand engineering, biomaterials, nanosensors, and synthetic biology. Although Protein Design is a challenging problem, proteins can be designed by experts in Protein Design, …
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A programmable DNA roadblock system using dCas9 and multivalent target sites | PLOS ONE

A programmable DNA roadblock system using dCas9 and multivalent target sites | PLOS ONE | SynBioFromLeukipposInstitute | Scoop.it
A protein roadblock forms when a protein binds DNA and hinders translocation of other DNA binding proteins. These roadblocks can have significant effects on gene expression and regulation as well as DNA binding. Experimental methods for studying the effects of such roadblocks often target endogenous sites or introduce non-variable specific sites into DNAs to create binding sites for artificially introduced protein roadblocks. In this work, we describe a method to create programmable roadblocks using dCas9, a cleavage deficient mutant of the CRISPR effector nuclease Cas9. The programmability allows us to custom design target sites in a synthetic gene intended for in vitro studies. These target sites can be coded with multivalency—in our case, internal restriction sites which can be used in validation studies to verify complete binding of the roadblock. We provide full protocols and sequences and demonstrate how to use the internal restriction sites to verify complete binding of the roadblock. We also provide example results of the effect of DNA roadblocks on the translocation of the restriction endonuclease NdeI, which searches for its cognate site using one dimensional diffusion along DNA.
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https://www.science.org/doi/10.1126/science.abo2781

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The fascinating world of biogenic crystals

 

Biogenic crystals are crystals that grow inside or under the influence of living organisms. These crystals are incredibly diverse, and the process of their growth is extremely complex. Despite their ubiquity, only several dozen biogenic crystals have been identified and studied. On page 312 of this issue, Avrahami et al. (1) present studies of coccoliths, which are micrometer-sized calcite (CaCO3) single plates formed by coccolithophores, a type of single-celled algae. The coccolithophores form around themselves a calcite shell called a coccosphere, which is composed of dozens of coccolith plates. Before discussing the most important and specific aspects of this study, it is worth exploring the diverse world of biogenic crystals.

 

https://www.science.org/doi/10.1126/science.abo2781

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https://www.sciencedirect.com/science/article/abs/pii/S0734975022000490

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Living building blocks | Nature Materials

Living building blocks | Nature Materials | SynBioFromLeukipposInstitute | Scoop.it
A prototypical biocomposite block comprising a blend of bacteria, fungi and feedstock can be assembled into human-sized, living structures with self-healing and environmental sensing capabilities.
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New DNA Computer Assesses Water Quality: Genetic Networks Mimic Electronic Circuits

New DNA Computer Assesses Water Quality: Genetic Networks Mimic Electronic Circuits | SynBioFromLeukipposInstitute | Scoop.it
Genetic networks mimic electronic circuits to perform a range of logic functions. Equipped with a series of eight small test tubes, the device glows green when it detects a contaminant. The number of tubes that glow depend upon how much contamination is present. If only one tube glows, then the w
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Researchers take 'protein circuits' a step closer to cell-to-cell communication

Researchers take 'protein circuits' a step closer to cell-to-cell communication | SynBioFromLeukipposInstitute | Scoop.it
Through synthetic biology, scientists can add novel functions to cells, such as the ability to produce new materials or detect and respond in specific ways to diseases. Though the applications are exciting, the process suffers from some inefficiencies—one of which Stanford University chemical engineer Xiaojing Gao is working to avoid.
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showPdf?pii=S0092-8674%2821%2901488-4

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Fundamental behaviors emerge from simulations of a living minimal cell

 

A kinetic model for a minimal bacterial cell offers quantitative insight into how the cell balances processes from metabolism to gene expression to growth.

 

https://www.cell.com/action/showPdf?pii=S0092-8674%2821%2901488-4

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Kinematic self-replication in reconfigurable organisms | PNAS

Kinematic self-replication in reconfigurable organisms | PNAS | SynBioFromLeukipposInstitute | Scoop.it
Reconfigurable organisms and dissociated stem cells were simulated as elastic voxels using a version of a voxel-based soft-body simulator (40) modified to run on highly parallelized (GPU-based) computing platforms (SI Appendix, Fig. S5).
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Synthetic biology: at the crossroads of genetic engineering and human therapeutics-a Keystone Symposia report

Synthetic biology: at the crossroads of genetic engineering and human therapeutics-a Keystone Symposia report | SynBioFromLeukipposInstitute | Scoop.it
Synthetic biology has the potential to transform cell- and gene-based therapies for a variety of diseases. Sophisticated tools are now available for both eukaryotic and prokaryotic cells to engineer cells to selectively achieve therapeutic effects in response to one or more disease-related signals, …
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Cell-free riboswitches

Cell-free riboswitches | SynBioFromLeukipposInstitute | Scoop.it
The emerging community of cell-free synthetic biology aspires to build complex biochemical and genetic systems with functions that mimic or even exceed those in living cells. To achieve such functions, cell-free systems must be able to sense and respond to the complex chemical signals within and out …
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Adaptive Circuits in Synthetic Biology - ScienceDirect

Adaptive Circuits in Synthetic Biology - ScienceDirect | SynBioFromLeukipposInstitute | Scoop.it
One of the most remarkable features of biological systems is their ability to adapt to the constantly changing environment. By harnessing principles o…
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hECA: The cell-centric assembly of a cell atlas

hECA: The cell-centric assembly of a cell atlas | SynBioFromLeukipposInstitute | Scoop.it
Cell biology; Stem cells research; Bioinformatics.
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Synthetic biology and bioelectrochemical tools for electrogenetic system engineering

Synthetic biology research and its industrial applications rely on deterministic spatiotemporal control of gene expression. Recently, electrochemical control of gene expression has been demonstrated in electrogenetic sys- tems (redox-responsive promoters used alongside redox inducers and electrodes), allowing for the direct inte- gration of electronics with biological processes. However, the use of electrogenetic systems is limited by poor activity, tunability, and standardization. In this work, we developed a strong, unidirectional, redox-responsive promoter before deriving a mutant promoter library with a spectrum of strengths. We constructed genetic circuits with these parts and demonstrated their activation by multiple classes of redox molecules. Last, we demonstrated electrochemical activation of gene expression under aerobic conditions using a novel, modular bioelectro- chemical device. These genetic and electrochemical tools facilitate the design and improve the performance of electrogenetic systems. Furthermore, the genetic design strategies used can be applied to other redox-responsive promoters to further expand the available tools for electrogenetics.

 

https://www.science.org/doi/pdf/10.1126/sciadv.abm5091

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Self-organized collective cell behaviors as design principles for synthetic developmental biology

Over the past two decades, molecular cell biology has graduated from a mostly analytic science to one with substantial synthetic capability. This success is built on a deep understanding of the structure and function of biomolecules and molecular mechanisms. For synthetic biology to achieve similar success at the scale of tissues and organs, an equally deep understanding of the principles of development is required. Here, we review some of the central concepts and recent progress in tissue patterning, morphogenesis and collective cell migration and discuss their value for synthetic developmental biology, emphasizing in particular the power of (guided) self-organization and the role of theoretical advances in making developmental insights applicable in synthesis.

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https://www.researchgate.net/publication/360038563_Self-organized_collective_cell_behaviors_as_design_principles_for_synthetic_developmental_biology

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Computational design of novel protein-protein interactions - An overview on methodological approaches and applications

Protein-protein interactions (PPIs) govern numerous cellular functions in terms of signaling, transport, defense and many others. Designing novel PPIs poses a fundamental challenge to our understanding of molecular interactions. The capability to robustly engineer PPIs has immense potential for the …
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Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome

Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome | SynBioFromLeukipposInstitute | Scoop.it
A computational and experimental strategy was developed to redesign biosynthetic gene
clusters into synthetic genetic elements that can be expressed across a wide range
of prokaryote and eukaryote hosts, expanding our ability to discover and characterize
a variety of natural products and biosynthetic pathways.
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Programmable molecular transport achieved by engineering protein motors to move on DNA nanotubes

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https://www.science.org/doi/10.1126/science.abj5170

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Synthetic mammalian signaling circuits for robust cell population control

Synthetic mammalian signaling circuits for robust cell population control | SynBioFromLeukipposInstitute | Scoop.it
Mammalian cells were engineered with both a plant hormone system, which provides a
diffusive communication channel, and robust synthetic signaling pathways that allow
for population sensing and control through auxin.
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Helical structure motifs made searchable for functional peptide design - PMC

Helical structure motifs made searchable for functional peptide design - PMC | SynBioFromLeukipposInstitute | Scoop.it
The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation
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2021.05.17.444437.full.pdf

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Fluorinated oil-surfactant mixtures with the density of water: artificial cells for synthetic biology

 

There is a rising interest in biotechnology for the compartmentalization of biochemical reactions in water droplets. Several applications, such as the widely used digital PCR, seek to encapsulate a single molecule in a droplet to be amplified. Directed evolution, another technology with growing popularity, seeks to replicate what happens in nature by encapsulating a single gene and the protein encoded by this gene, linking genotype with phenotype. Compartmentalizing reactions in droplets also allows the experimentalist to run millions of different reactions in parallel. Compartmentalization requires a fluid that is immiscible with water and a surfactant to stabilize the droplets. While there are fluids and surfactants on the market that have been used to accomplish encapsulation, there are reported concerns with these. Span® 80, for example, a commonly used surfactant, has contaminants that interfere with various biochemical reactions. Similarly, synthetic fluids distributed by the cosmetic industry allow some researchers to produce experimental results that can be published, but then other researchers fail to reproduce some of these protocols due to the unreliable nature of these products, which are not manufactured with the intent of being used in biotechnology. The most reliable fluids, immiscible with water and suitable for biochemical reactions, are fluorinated fluids. Fluorinated compounds have the peculiar characteristic of being immiscible with water while at the same time not mixing with hydrophobic molecules. This peculiar characteristic has made fluorinated fluids attractive because it seems to be the basis of their being biologically inert. However, commercially available fluorinated fluids have densities between 1.4 to 1.6 g/mL. The higher-than-water density of fluorinated oils complicates handling of the droplets since these would float on the fluid since the water droplets would be less dense. This can cause aggregation and coalescence of the droplets. Here, we report the synthesis, characterization, and use of fluorinated polysiloxane oils that have densities similar to the one of water at room temperature, and when mixed with non-ionic fluorinated surfactants, can produce droplets encapsulating biochemical reactions. We show how droplets in these emulsions can host many biological processes, including PCR, DNA origami, rolling circle amplification (RCA), and Taqman® assays. Some of these use 

unnatural DNA built from an Artificially Expanded Genetic Information System (AEGIS) with six nucleotide "letters"

 

https://www.biorxiv.org/content/biorxiv/early/2021/12/17/2021.05.17.444437.full.pdf

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Artificial intelligence powers protein-folding predictions

Artificial intelligence powers protein-folding predictions | SynBioFromLeukipposInstitute | Scoop.it
Deep-learning algorithms such as AlphaFold2 and RoseTTAFold can now predict a protein’s 3D shape from its linear sequence — a huge boon to structural biologists.
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Computed structures of core eukaryotic protein complexes

Computed structures of core eukaryotic protein complexes | SynBioFromLeukipposInstitute | Scoop.it
Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions not yet identified. We tak
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Computational Framework for Machine-Learning-Enabled 13 C Fluxomics

Computational Framework for Machine-Learning-Enabled 13 C Fluxomics | SynBioFromLeukipposInstitute | Scoop.it
13C metabolic flux analysis (MFA) has emerged as a powerful tool for synthetic biology. This optimization-based approach suffers long computation time and unstable solutions depending on the initial guess. Here, we develop a machine-learning-based framework for 13C fluxomics. S
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