Lifeboat Foundation

When cells reproduce, the internal mechanisms that copy DNA get it right nearly every time. Rice University bioscientists have uncovered a tiny detail that helps understand how the process could go wrong.

Their study of enzymes revealed the presence of a central metal ion critical to DNA replication also appears to be implicated in misincorporation, the faulty ordering of nucleotides on new strands.

Continue reading “Crystal study may resolve DNA mystery” »

CRISPR-Cas9 is considered a revolutionary gene editing tool, but its applications are limited by a lack of methods by which it can be safely and efficiently delivered into cells. Recently, a research team from Kumamoto University, Japan, have constructed a highly flexible CRISPR-Cas9 carrier using aminated polyrotaxane (PRX) that can not only bind with the unusual structure of Cas9 and carry it into cells, but can also protect it from intracellular degradation by endosomes.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their accompanying protein, CRISPR-associated protein 9 (Cas9), made international headlines a few years ago as a game-changing genome editing system. Consisting of Cas9 and strand of genetic material known as a single-guide RNA (sgRNA), the system can target specific regions of DNA and function as “molecular scissors” to make precise edits. The direct delivery of Cas9–sgRNA complexes, i.e. Cas9 ribonucleoproteins (RNPs), into the nucleus of the cell is considered the safest and most efficient way to achieve genome editing. However, the Cas9 RNP has poor cellular permeability, and thus requires a carrier molecule to transport it past the first hurdle of the cell membrane before it can get to the cell nucleus. These carriers need to bind with Cas9 RNP, carry it into the cell, prevent its degradation by intracellular organelles called “endosomes,” and finally release it without causing any changes to its structure.

In a recent paper published in the June 2022, Volume 27 of Applied Materials Today, a research team from Kumamoto University has developed a transformable polyrotaxane (PRX) carrier that can facilitate genome editing using Cas9RNP with high efficiency and usability. “While there have been some PRX-based drug carriers for nucleic acids and proteins reported before, this is the first report on PRX-based Cas9 RNP carrier. Moreover, our findings describe how to precisely control intracellular dynamics across multiple steps. This will prove invaluable for future research in this direction,” says Professor Keiichi Motoyama, a corresponding author of the paper.

When genes mutate, it can result in severe diseases of the human nervous system. Neuroscientists at Leipzig University and the University of Würzburg have now used fruit flies to demonstrate how, apart from the negative effect, the mutation of a neuronal gene can have a positive effect – namely higher IQ in humans. They have published their findings in the prestigious journal Brain.

Synapses are the contact points in the brain via which nerve cells ‘talk’ to one another. Disruptions in this communication lead to nervous system diseases, since altered synaptic proteins, for example, can impair this complex molecular mechanism. This can cause mild symptoms, but also very severe disabilities in those affected.

The interest of the two neurobiologists Professor Tobias Langenhan and Professor Manfred Heckmann, from Leipzig and Würzburg respectively, was aroused when they read in a scientific publication about a mutation that damages a synaptic protein. At first, the affected patients attracted scientists’ attention because the mutation caused them to go blind. However, doctors then noticed that the patients were also of above-average intelligence. “It’s very rare for a mutation to lead to improvement rather than loss of function,” says Langenhan, professor and holder of a chair at the Rudolf Schönheimer Institute of Biochemistry at the Faculty of Medicine.

The latest “machine scientist” algorithms can take in data on dark matter, dividing cells, turbulence, and other situations too complicated for humans to understand and provide an equation capturing the essence of what’s going on.

Despite rediscovering Kepler’s third law and other textbook classics, BACON remained something of a curiosity in an era of limited computing power. Researchers still had to analyze most data sets by hand, or eventually with Excel-like software that found the best fit for a simple data set when given a specific class of equation. The notion that an algorithm could find the correct model for describing any data set lay dormant until 2009, when Lipson and Michael Schmidt, roboticists then at Cornell University, developed an algorithm called Eureqa.

Their main goal had been to build a machine that could boil down expansive data sets with column after column of variables to an equation involving the few variables that actually matter. “The equation might end up having four variables, but you don’t know in advance which ones,” Lipson said. “You throw at it everything and the kitchen sink. Maybe the weather is important. Maybe the number of dentists per square mile is important.”

Continue reading “‘Machine Scientists’ Distill the Laws of Physics From Raw Data” »

It is vital to recognize the immediate economic importance of i nvesting in longevity and healthy-aging sciences.

Aging itself is a complex series of at least 300 biological processes involving more than 10% of our genetic makeup. It follows that methods to combat these effects must be a combination of sciences, from biotech to biophysics and pharmaceuticals. There is no single “silver bullet” solution.

Aging, along with the physical and mental decay that accompanies it, is still widely regarded as a natural and inevitable thing. It is not, it is a degenerative disease in which the physical integrity and structure of our cells decay each time they divide to replace old ones or as part of any healing process.

The results of the study could lead to new treatment options. In a groundbreaking new study published in the journal Nature on Thursday, researchers have compared the brain cells of patients who had died from either Parkinson’s disease or dementia to people unaffected by the disorders and found which brain cells are responsible for both conditions.

A team of researchers has created a bacteria that can produce a steady and consistent source of medicine inside a patient’s gut, suggesting the possibility for genetically edited bacteria to be an efficient Parkinson’s disease treatment.

Continue reading “Scientists engineer a bacteria to produce a drug used to treat Parkinson’s disease” »

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Scientists have uncovered changes in neurological structure that could underlie the autism spectrum disorder known as Pitt Hopkins syndrome, thanks to the help of lab-grown brains developed from human cells.

Furthermore, the researchers were able to recover lost genetic functions through the use of two different gene therapy strategies – hinting at the possibility of treatments that could one day give those with the condition new options in improving their quality of life.

Pitt Hopkins syndrome is a neurodevelopmental condition stemming from a mutation in a DNA-management gene called transcription factor 4 (TCF4). Classed on the autism spectrum on account of its severe impact on motor skills and sensory integration, it’s a complex condition that presents with a range of severities.

Using new analyses, scientists have just found the last two of the five informational units of DNA and RNA that had yet to be discovered in samples from meteorites. While it is unlikely that DNA could be formed in a meteorite, this discovery demonstrates that these genetic parts are available for delivery and could have contributed to the development of the instructional molecules on early Earth. The discovery, by an international team with NASA researchers, gives more evidence that chemical reactions in asteroids can make some of life’s ingredients, which could have been delivered to ancient Earth by meteorite impacts or perhaps the infall of dust.

All DNA and RNA, which contains the instructions to build and operate every living being on Earth, contains five informational components, called nucleobases. Until now, scientists scouring extraterrestrial samples had only found three of the five. However, a recent analysis by a team of scientists led by Associate Professor Yasuhiro Oba of Hokkaido University, Hokkaido, Japan, identified the final two nucleobases that have eluded scientists.

Nucleobases belong to classes of organic molecules called purines and pyrimidines, which have a wide variety. However, it remains a mystery why more types haven’t been discovered in meteorites so far.