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In a discovery with wide-ranging implications, researchers at the University of Massachusetts Amherst recently announced in the Proceedings of the National Academy of Sciences that uniformly charged macromolecules—or molecules, such as proteins or DNA, that contain a large number of atoms all with the same electrical charge—can self-assemble into very large structures. This finding upends our understanding of how some of life’s basic structures are built.
Traditionally, scientists have understood charged polymer chains as being composed of smaller, uniformly charged units. Such chains, called polyelectrolytes, display predictable behaviors of self-organization in water: They will repel each other because similarly charged objects don’t like to be close to each other. If you add salt to water containing polyelectrolytes, then molecules coil up, because the chains’ electrical repulsion is screened by the salt.
However, “the game is very different when you have dipoles,” says Murugappan Muthukumar, the Wilmer D. Barrett Professor in Polymer Science and Engineering at UMass Amherst, the study’s senior author.
This year’s Breakthrough Prize in Life Sciences has a strong physical sciences element. The prize was divided between six individuals. Demis Hassabis and John Jumper of the London-based AI company DeepMind were awarded a third of the prize for developing AlphaFold, a machine-learning algorithm that can accurately predict the 3D structure of proteins from just the amino-acid sequence of their polypeptide chain. Emmanuel Mignot of Stanford University School of Medicine and Masashi Yanagisawa of the University of Tsukuba, Japan, were awarded for their work on the sleeping disorder narcolepsy.
The remainder of the prize went to Clifford Brangwynne of Princeton University and Anthony Hyman of the Max Planck Institute of Molecular Cell Biology and Genetics in Germany for discovering that the molecular machinery within a cell—proteins and RNA—organizes by phase separating into liquid droplets. This phase separation process has since been shown to be involved in several basic cellular functions, including gene expression, protein synthesis and storage, and stress responses.
The award for Brangwynne and Hyman shows “the transformative role that the physics of soft matter and the physics of polymers can play in cell biology,” says Rohit Pappu, a biophysicist and bioengineer at Washington University in St. Louis. “[The discovery] could only have happened the way it did: a creative young physicist working with an imaginative cell biologist in an ecosystem where boundaries were always being pushed at the intersection of multiple disciplines.”
All eyes are on the Emerald Isle this week as the Longevity Summit Dublin brings together a host of speakers covering the spectrum of this booming sector. Delegates have been hearing from some of the leading entrepreneurs, companies, investors, and researchers in the field as they address many of the hot-button topics affecting longevity. One of those speakers is the so-called “father of genomics” – Harvard professor of genetics, George Church – who closes the conference later today with a keynote on Gene, cell and organ therapies for de-aging.
Longevity. Technology: In addition to his Harvard professorship, Church heads up synthetic biology at the Wyss Institute, where he oversees development of new tools with applications in regenerative medicine. Much of his focus more recently has been on the development of gene therapies targeting age-related disease, a passion that led him to co-found Rejuvenate Bio, with the goal of creating “full age reversal gene therapies.” We caught up with Church ahead of his Dublin presentation for a brief conversation on longevity.
Dr Church’s name is synonymous with genomic science, and he was a key contributor to the Human Genome Project and technologies including next-generation fluorescent and nanopore sequencing, aimed at understanding genetic contributions to human disease. However, he doesn’t feel that those initiatives did a huge amount to move the aging field forward.
Continue reading “George Church: Learn from COVID and fast-track therapies that reverse aging” »
Scientist from the National University of Singapore (NUS) have found a novel way of growing cell-based meat by zapping animal cells with a magnet. This new technique simplifies the production process of cell-based meat by reducing reliance on animal products, and it is also greener, cleaner, safer and more cost-effective.
Cultured meat is an alternative to animal farming with advantages such as reducing carbon footprint and the risk of transmitting diseases in animals. However, the current method of producing cultured meat involves using other animal products, which largely defeats the purpose, or drugs to stimulate the growth of the meat.
To cultivate cell-based meat, animal cells are fed animal serum—usually fetal bovine serum (FBS), which is a mixture harvested from the blood of fetuses excised from pregnant cows slaughtered in the dairy or meat industries—to help them grow and proliferate. This is a critical, yet cruel and expensive, step in the current cell-based meat production process. Ironically, many of these molecules come from the muscles within the slaughtered animal, but scientists did not know how to stimulate their release in production scale bioreactors. Other methods to promote cell growth are using drugs or relying on genetic engineering.
Ideally, the nanopore dimensions should be comparable to those of the analyte for the presence of the analyte to produce a measurable change in the ionic current amplitude above the noise level. Nanopores can be formed in several ways, with a wide range of pore diameters. Biological nanopores are formed by the self-assembly of either protein subunits, peptides or even DNA scaffolds in lipid bilayers or block copolymer membranes1,3,6,17,18. They possess atomically precise dimensions controlled by biopolymer sequences, providing the ability to recognize biomolecules with constriction diameters of ~1–10 nm. Solid-state nanopores are crafted in thin inorganic or plastic membranes (for example, SiNx), which allows the nanopores to have extended diameters of up to hundreds of nanometres, permitting the entry or analysis of large biomolecules and complexes. The tools for fabricating solid-state nanopores, which include electron/ion milling4,5, laser-based optical etching19,20 and the dielectric breakdown of ultrathin solid membranes21,22, can be used to manipulate nanopore size at the nanometre scale, but allow only limited control over the surface structure at the atomic level in contrast to biological nanopores. The chemical modification and genetic engineering of biological nanopores, or the introduction of biomolecules to functionalize solid-state nanopores23, can further enhance the interactions between a nanopore and analytes, improving the overall sensitivity and selectivity of the device2,17,24,25,26. This feature allows nanopores to controllably capture, identify and transport a wide variety of molecules and ions from bulk solution.
Nanopore technology was initially developed for the practicable stochastic sensing of ions and small molecules2,27,28. Subsequently, many developmental efforts were focused on DNA sequencing1,7,8,9. Now, however, nanopore applications extend well beyond sequencing, as the methodology has been adapted to analyse molecular heterogeneities and stochastic processes in many different biochemical systems (Fig. 1). First, a key advantage of nanopores lies in their ability to successively capture many single molecules one after the other at a relatively high rate, which allows nanopores to explore large populations of molecules at the single-molecule level in reasonable timeframes. Second, nanopores essentially convert the structural and chemical properties of the analytes into a measurable ionic current signal, even achieving enantiomer discrimination29. The technology can be used to report on multiple molecular features while circumventing the need for labelling chemistries, which may complicate the overall analysis process and affect the molecular structures. For example, nanopores can discriminate nearly 13 different amino acids in a label-free manner, including some with minute structural differences30. An important aspect is the ability of nanopores to identify species31 that lack suitable labels for signal amplification or whose information is hidden in the noise of analytical devices. Consequently, nanopores may serve well in molecular diagnostic applications required for precision medicine, which achieves the identification of nucleic acid, protein or metabolite analytes and other biomarkers11,32,33,34,35. Third, nanopores provide a well-defined scaffold for controllably designing and constructing biomimetic systems, which involve a complex network of biomolecular interactions. These nanopore systems track the binding dynamics of transported biomolecules as they interact with nanopore surfaces, hence serving as a platform for unravelling complex biological processes (for example, the transport properties of nuclear pore complexes)36,37,38,39. Fourth, chemical groups can be spatially aligned within a protein nanopore, providing a confined chemical environment for site-selective or regioselective covalent chemistry. This strategy has been used to engineer protein nanoreactors to monitor bond-breaking and bond-making events40,41.
Here we discuss the latest advances in nanopore technologies beyond DNA sequencing and the future trajectory of the field, as well as the opportunities and main challenges for the next decade. We specifically address the emerging nanopore methods for protein analysis and protein sequencing, single-molecule covalent chemistry, single-molecule analysis of clinical samples and insights into the use of biomimetic pores for analysing complex biological processes.
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LA JOLLA—Salk scientists have created a new version of the CRISPR/Cas9 genome editing technology that allows them to activate genes without creating breaks in the DNA, potentially circumventing a major hurdle to using gene editing technologies to treat human diseases.
In a clinical trial, the first patient has received a single dose of a new human immunodeficiency virus (HIV) gene editing therapy, researchers at the Lewis Katz School of Medicine at Temple University and Excision BioTherapeutics, Inc have reported.
In a collaborative effort, the researchers are currently running a phase 1/2 clinical trial to evaluate the safety and efficacy of their therapy, called EBT-101, which is based on gene editing technology known as CRISPR.
Continue reading “CRISPR-Based HIV Gene Therapy Administered To First Human Patient” »
When the inside of a mollusk shell shimmers in sunlight, the iridescence isn’t produced by colored pigments but by tiny physical structures self-assembled from living cells and inorganic components. Now, a team of researchers at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has developed a platform to mimic this self-assembly ability by engineering living cells to act as a starting point for building composite materials.
Engineered living materials (ELMs) use living cells as “materials scaffolds” and are a new class of material that might open the door to self-healing materials and other advanced applications in bioelectronics, biosensing, and smart materials. Such materials could mimic emergent properties found in nature—where a complex system has properties that the individual components do not have—such as iridescence or strength.
Borrowing from this complexity seen in nature, the Berkeley Lab researchers engineered a bacterium that can attach a wide range of nanomaterials to its cell surface. They can also precisely control the makeup and how densely packed the components are, creating a stable hybrid living material. The study describing their work was recently published in ACS Synthetic Biology.
Chromosome-level engineering is a completely different beast: it’s like rearranging multiple paragraphs or shifting complete sections of an article and simultaneously hoping the changes add capabilities that can be passed onto the next generation.
Reprogramming life isn’t easy. Xiao Zhu’s DNA makeup is built from genetic letters already optimized by eons of evolutionary pressure. It’s no surprise that tinkering with an established genomic book often results in life that’s not viable. So far, only yeast have survived the rejiggering of their chromosomes.
The new study, published in Science, made the technology possible for mice. The team artificially fused together chunks from mice chromosomes. One fused pair made from chromosomes four and five was able to support embryos that developed into healthy—if somewhat strangely behaved—mice. Remarkably, even with this tectonic shift to their normal genetics, the mice could reproduce and pass on their engineered genetic quirks to a second generation of offspring.
Continue reading “Scientists Use CRISPR to Condense a Million Years of Evolution Into Mere Months” »
