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Category: genetics – Page 103

Beyond CRISPR: seekRNA delivers a New Pathway for Accurate Gene Editing

Scientists at the University of Sydney have developed a gene-editing tool with greater accuracy and flexibility than the industry standard, CRISPR, which has revolutionized genetic engineering in medicine, agriculture and biotechnology.

SeekRNA uses a programmable ribonucleic acid (RNA) strand that can directly identify sites for insertion in genetic sequences, simplifying the editing process and reducing errors.

The new gene-editing tool is being developed by a team led by Dr. Sandro Ataide in the School of Life and Environmental Sciences. Their findings have been published in Nature Communications.

Noninvasive Alternative to Cancer Biopsy

The path toward a cancer diagnosis is anything but fun. Among the least enjoyable aspects of the journey are the invasive and often excruciating biopsies that are needed to collect information about the genetic mutations or chromosomal abnormalities of the cells in a growing tumor. This information is critical for an accurate diagnosis of a patient’s cancer, as well as for prognosis predictions and treatment selections. At the recent Acoustical Society of America meeting in Ottawa, Canada, Roger Zemp of the University of Alberta reported on an alternative method that he and his colleagues have developed for extracting this genetic information that uses sound waves rather than tissue removal. “Traditional biopsies with their big needles are scary and painful,” says Joy Wang, a master’s student who works with Zemp. “Our method is pain free and can provide clearer information about a cancer’s genetics.”

Biopsy needles are akin to hole punches for the flesh. These long, hollow needles can be over 2 mm in diameter and typically punch out a core of flesh between 1 and 2 mm in diameter. For comparison, the average blood-draw needle is half a millimeter in diameter. The large holes made by the biopsy needles significantly increase the likelihood of pain, swelling, bruising, or infection at the biopsy site, both during the biopsy collection and for days afterward.

The prospect of being left black and blue can cause patients significant anxiety. The worry can become so high that it can stop a person from getting a questionable lump or bump checked out. Therefore, researchers have been searching for less invasive, less frightening methods to retrieve the information that biopsies provide. Alternative techniques could also allow for earlier detection of some cancers, Zemp says.

Beyond CRISPR: Scientists Say New Gene Editing Tool Is Like a ‘Word Processor’ for DNA

“Bridge recombination can universally modify genetic material through sequence-specific insertion, excision, inversion, and more, enabling a word processor for the living genome beyond CRISPR,” said Berkeley’s Patrick Hsu, a senior author of one of the studies and Arc Institute core investigator, in a press release.

CRISPR Coup

Scientists first discovered CRISPR in bacteria defending themselves against viruses. In nature, a Cas9 protein pairs with an RNA guide molecule to seek out viral DNA and, when located, chop it up. Researchers learned to reengineer this system to seek out any DNA sequence, including sequences found in human genomes, and break the DNA strands at those locations. The natural machinery of the cell then repairs these breaks, sometimes using a provided strand of DNA.

Unlocking the Secrets of LUCA, Earth’s Earliest Life Form

A University of Bristol-led study found that life on Earth, stemming from a common ancestor called LUCA, flourished soon after the planet’s formation.

Through genetic analysis and evolutionary modeling, researchers pinpointed LUCA’s existence to about 4.2 billion years ago, revealing it as a complex organism with an early immune system integral to Earth’s earliest ecosystems.

Luca’s genetic blueprint and its descendants.

HUN-REN BRC researchers develop laser-guided microrobots for cell-capturing

This is pretty impressive, they can move around individual cells. Video in comments:

Researchers at the HUN-REN Biological Research Centre, Szeged, have developed tiny tools to capture individual cells. According to their study published in the journal Advanced Materials, key innovations of using flexible microrobots is that they do not require any treatment of the cells to grab them and also allow the cells to be released after examination, enabling more efficient investigations than ever before.

Single-cell investigation methods such as single-cell genetics, proteomics, or imaging-based morphological classification have risen to the forefront of biological research in the last decade. These methods require precisely controlled physical manipulation of individual cells on the microscopic scale. This manipulation at the single-cell level means their transportation and rotation in a controlled manner, for which several methods have been developed over the last decades. These cutting-edge methods use active movable microtools such as microgrippers similar in size to the cells, complex electrophoretic systems that use high-frequency electric fields to move the cells, or optothermal traps that create liquid flow through localised laser heating. The technique of optical tweezers fits into this category, being one of the most efficient single-cell manipulation methods and was awarded a Nobel prize in 2018.

Century-Old Biological Experiment Reveals Genetic Secrets of Important Crop

A long-term study since 1929 has revealed significant insights into barley’s evolution, showing its adaptation to different environments and the substantial impact of natural selection. This research underscores the limitations of evolutionary breeding and highlights the need for further exploration to enhance crop yields.

Utilizing one of the world’s oldest biological experiments, which commenced in 1929, researchers have revealed how barley, a major crop, has been influenced by agricultural pressures and its evolving natural environment. These findings highlight the significance of long-term studies in comprehending the dynamics of adaptive evolution.

The survival of cultivated plants after their dispersal across different environments is a classic example of rapid adaptive evolution. For example, barley, an important neolithic crop, spread widely after domestication over 10,000 years ago to become a staple source of nutrition for humans and livestock throughout Europe, Asia, and Northern Africa over just a few thousand generations. Such rapid expansion and cultivation have subjected the plant to strong selective pressures, including artificial selection for desired traits and natural selection by being forced to adapt to diverse new environments.

Modeling the origins of life: New evidence for an “RNA World”

LA JOLLA (March 4, 2024)—Charles Darwin described evolution as “descent with modification.” Genetic information in the form of DNA sequences is copied and passed down from one generation to the next. But this process must also be somewhat flexible, allowing slight variations of genes to arise over time and introduce new traits into the population.

But how did all of this begin? In the origins of life, long before cells and proteins and DNA, could a similar sort of evolution have taken place on a simpler scale? Scientists in the 1960s, including Salk Fellow Leslie Orgel, proposed that life began with the “RNA World,” a hypothetical era in which small, stringy RNA molecules ruled the early Earth and established the dynamics of Darwinian evolution.

New research at the Salk Institute now provides fresh insights on the origins of life, presenting compelling evidence supporting the RNA World hypothesis. The study, published in Proceedings of the National Academy of Sciences (PNAS) on March 4, 2024, unveils an RNA enzyme that can make accurate copies of other functional RNA strands, while also allowing new variants of the molecule to emerge over time. These remarkable capabilities suggest the earliest forms of evolution may have occurred on a molecular scale in RNA.

The nature of the last universal common ancestor and its impact on the early Earth system

Life’s evolutionary timescale is typically calibrated to the oldest fossil occurrences. However, the veracity of fossil discoveries from the early Archaean period has been contested11,12. Relaxed Bayesian node-calibrated molecular clock approaches provide a means of integrating the sparse fossil and geochemical record of early life with the information provided by molecular data; however, constraining LUCA’s age is challenging due to limited prokaryote fossil calibrations and the uncertainty in their placement on the phylogeny. Molecular clock estimates of LUCA13,14,15 have relied on conserved universal single-copy marker genes within phylogenies for which LUCA represented the root. Dating the root of a tree is difficult because errors propagate from the tips to the root of the dated phylogeny and information is not available to estimate the rate of evolution for the branch incident on the root node. Therefore, we analysed genes that duplicated before LUCA with two (or more) copies in LUCA’s genome16. The root in these gene trees represents this duplication preceding LUCA, whereas LUCA is represented by two descendant nodes. Use of these universal paralogues also has the advantage that the same calibrations can be applied at least twice. After duplication, the same species divergences are represented on both sides of the gene tree17,18 and thus can be assumed to have the same age. This considerably reduces the uncertainty when genetic distance (branch length) is resolved into absolute time and rate. When a shared node is assigned a fossil calibration, such cross-bracing also serves to double the number of calibrations on the phylogeny, improving divergence time estimates. We calibrated our molecular clock analyses using 13 calibrations (see ‘Fossil calibrations’ in Supplementary Information). The calibration on the root of the tree of life is of particular importance. Some previous studies have placed a younger maximum constraint on the age of LUCA based on the assumption that life could not have survived Late Heavy Bombardment (LHB) (~3.7–3.9 billion years ago (Ga))19. However, the LHB hypothesis is extrapolated and scaled from the Moon’s impact record, the interpretation of which has been questioned in terms of the intensity, duration and even the veracity of an LHB episode20,21,22,23. Thus, the LHB hypothesis should not be considered a credible maximum constraint on the age of LUCA. We used soft-uniform bounds, with the maximum-age bound based on the time of the Moon-forming impact (4,510 million years ago (Ma) ± 10 Myr), which would have effectively sterilized Earth’s precursors, Tellus and Theia13. Our minimum bound on the age of LUCA is based on low δ98 Mo isotope values indicative of Mn oxidation compatible with oxygenic photosynthesis and, therefore, total-group Oxyphotobacteria in the Mozaan Group, Pongola Supergroup, South Africa24,25, dated minimally to 2,954 Ma ± 9 Myr (ref. 26).

Our estimates for the age of LUCA are inferred with a concatenated and a partitioned dataset, both consisting of five pre-LUCA paralogues: catalytic and non-catalytic subunits from ATP synthases, elongation factor Tu and G, signal recognition protein and signal recognition particle receptor, tyrosyl-tRNA and tryptophanyl-tRNA synthetases, and leucyl-and valyl-tRNA synthetases27. Marginal densities (commonly referred to as effective priors) fall within calibration densities (that is, user-specified priors) when topologically adjacent calibrations do not overlap temporally, but may differ when they overlap, to ensure the relative age relationships between ancestor-descendant nodes. We consider the marginal densities a reasonable interpretation of the calibration evidence given the phylogeny; we are not attempting to test the hypothesis that the fossil record is an accurate temporal archive of evolutionary history because it is not28.

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