Lifeboat Foundation

An interdisciplinary team of mathematicians, engineers, physicists, and medical scientists has discovered a surprising connection between pure mathematics and genetics. This connection sheds light on the structure of neutral mutations and the evolution of organisms.

Number theory, the study of the properties of positive integers, is perhaps the purest form of mathematics. At first sight, it may seem far too abstract to apply to the natural world. In fact, the influential American number theorist Leonard Dickson wrote “Thank God that number theory is unsullied by any application.”

And yet, again and again, number theory finds unexpected applications in science and engineering, from leaf angles that (almost) universally follow the Fibonacci sequence, to modern encryption techniques based on factoring prime numbers. Now, researchers have demonstrated an unexpected link between number theory and evolutionary genetics.

Each cell in the body stores its genetic information in DNA in a stable and protected form that is readily accessible for the cell to carry on its activities. Nevertheless, mutations—changes in genetic information—occur throughout the human genome and can have a powerful influence on human health and evolution.

“Our team is interested in a classical question about mutation—why do mutation rates in the genome vary so tremendously from one DNA location to another? We just do not have a clear understanding of why this occurs,” said Dr. Md. Abul Hassan Samee, assistant professor of integrative physiology at Baylor College of Medicine and corresponding author of the work.

Previous studies have shown that the DNA sequences flanking a mutated position—the sequence context—play a strong role in the mutation rate. “But this explanation still leaves unanswered questions,” Samee said. “For example, one type of mutation occurs frequently in a specific sequence context while a different type of mutation occurs infrequently in that same sequence context. So, we think that a different mechanism could explain how mutation rates vary in the genome. We know that each building block or base that makes up a DNA sequence has its own 3D chemical shape. We proposed, therefore, that there is a connection between DNA shape and mutations rates, and this paper shows that our idea was correct.”

Heterochronic parabiosis ameliorates age-related diseases in mice, but how it affects epigenetic aging and long-term health was not known. Here, the authors show that in mice exposure to young circulation leads to reduced epigenetic aging, an effect that persists for several months after removing the youthful circulation.

Yang and co-workers state that “using inducible changes to the epigenome, we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.” There is extensive evidence that the key reagent, restriction endonuclease I-PpoI, is cytotoxic. Moreover, the corresponding author published two papers—neither cited—showing that I-PpoI targeted to specific cell types causes a p53 response and cell elimination within a month. Despite globally inducing I-PpoI activation for seven times as long as required to induce a progeric effect, no analysis of mice during this critical window was presented. No significant conclusion of Yang was demonstrated.

They call it the ‘missing link.’

A pioneering dental medicine project in Japan is making strides toward clinical trials, with the aim of becoming the world’s first tooth-regrowing treatment, according to the country’s national news site Mainichi.

The upcoming trial will be focused on patients affected by anodontia, a genetic condition characterized by the absence of teeth, or partial anodontia, where people are missing some teeth, as described by the National Organization for Rare Disorders (NORD).

Clinical trials are scheduled to begin next July in Japan. If successful, regulatory approval for the tooth-regrowing medicine is anticipated by 2030, potentially heralding groundbreaking advancements in dentistry.

Microorganisms leverage the CRISPR-Cas system as a defense mechanism against viral intrusions. In the realm of genetic engineering, this microbial immune system is repurposed for the targeted modification of the genetic makeup.

Under the leadership of Professor Dr. Alexander Probst, microbiologist at the Research Center One Health Ruhr at the Research Alliance Ruhr a research team has now discovered another function of this specialised genomic sequence: archaea – microorganisms that are often very similar to bacteria in appearance – also use them to fight parasites.

The team has recently published their findings in Nature Microbiology.

If two statisticians were to lose each other in an infinite forest, the first thing they would do is get drunk. That way, they would walk more or less randomly, which would give them the best chance of finding each other. However, the statisticians should stay sober if they want to pick mushrooms. Stumbling around drunk and without purpose would reduce the area of exploration, and make it more likely that the seekers would return to the same spot, where the mushrooms are already gone.

Such considerations belong to the statistical theory of “random walk” or “drunkard’s walk,” in which the future depends only on the present and not the past. Today, random walk is used to model share prices, molecular diffusion, neural activity, and population dynamics, among other processes. It is also thought to describe how “genetic drift” can result in a particular gene—say, for blue eye color—becoming prevalent in a population. Ironically, this theory, which ignores the past, has a rather rich history of its own. It is one of the many intellectual innovations dreamed up by Andrei Kolmogorov, a mathematician of startling breadth and ability who revolutionized the role of the unlikely in mathematics, while carefully negotiating the shifting probabilities of political and academic life in Soviet Russia.

Thoughts?

Wearable electronic devices are playing a rapidly expanding role in the acquisition of individuals’ health data for personalized medical interventions; however, wearables cannot yet directly program gene-based therapies because of the lack of a direct electrogenetic interface. Here we provide the missing link by developing an electrogenetic interface that we call direct current (DC)-actuated regulation technology (DART), which enables electrode-mediated, time-and voltage-dependent transgene expression in human cells using DC from batteries. DART utilizes a DC supply to generate non-toxic levels of reactive oxygen species that act via a biosensor to reversibly fine-tune synthetic promoters.