Category Archives: DNA

Nobel Chemistry Prize Awarded For CRISPR ‘NanoScissors’

October 25, 2020   DNA   No comments

A humbling lesson of science is that, even when it comes to many of humanity’s most brilliant inventions, nature got there first. The 2020 selection for the Nobel Prize in Chemistry goes to two scientists who share credit for identifying and developing a revolutionary method of genome editing — one that has allowed researchers to modify and investigate the genomes of microbial, plant and animal cells with an ease, precision and effectiveness that would have been unfathomable even a decade ago. Yet the technology that came out of their work, revolutionary as it is, springs from an innovation that first evolved in bacteria, probably more than a billion years ago, and went unnoticed until recently.

Emmanuelle Charpentier (right) and Jennifer Doudna (left) have been awarded the 2020 Nobel Prize in Chemistry for their development of CRISPR/Cas9 genetic editing.

Emmanuelle Charpentier of the Max Planck Unit for the Science of Pathogens Institute for Infection Biology and Jennifer Doudna of the University of California, Berkeley have been recognized for their work on CRISPR/Cas9 genome editing — a technique routinely called CRISPR for short and often referred to as “genetic scissors.” This award marks the first time that two women have been award a Nobel Prize for science.

In a seminal 2012 paper, Charpentier and Doudna showed that key components of the ancient immune system found in bacteria and archaea could be retooled to edit DNA, to essentially “rewrite the code of life,” as the Nobel committee put it this morning.

In the eight years since, the discovery has transformed the life sciences, making genome editing commonplace in laboratories around the world. It has enabled researchers to probe the functions of genes at will, pushing the field of molecular biology ahead by leaps and bounds; to innovate new methods of plant breeding; and to develop promising new gene therapies, some now in clinical trials, for conditions such as sickle cell disease.

The Nobel committee’s selection will undoubtedly be greeted as controversial because of well-publicized disputes about the intellectual property associated with CRISPR. Virginijus Šikšnys of Vilnius University in Lithuania independently developed the idea of using these genetic features of bacteria as a genome-editing tool at about the same time as Charpentier and Doudna, and he has sometimes been honored alongside them. Two other scientists, Feng Zhang of the Massachusetts Institute of Technology and George Church of Harvard University, are also often credited as early co-discoverers and developers of CRISPR technology, and their exclusion will fuel arguments. However, no one in the scientific community would dispute that Charpentier and Doudna’s work laid the foundation for CRISPR’s prolific and game-changing use today.

Source: https://www.quantamagazine.org/

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Breaktrough In Regenerative Dentistry

October 11, 2020   DNA   No comments

New knowledge on the cellular makeup and growth of teeth can expedite developments in regenerative dentistry – a biological therapy for damaged teeth – as well as the treatment of tooth sensitivity. The study, which was conducted by researchers at Karolinska Institutet (Sweden), is published in Nature Communications.

Teeth develop through a complex process in which soft tissue, with connective tissue, nerves and blood vessels, are bonded with three different types of hard tissue into a functional body part. As an explanatory model for this process, scientists often use the mouse incisor, which grows continuously and is renewed throughout the animal’s life.

Despite the fact that the mouse incisor has often been studied in a developmental context, many fundamental questions about the various tooth cells, stem cells and their differentiation and cellular dynamics remain to be answered.

Using a single-cell RNA sequencing method and genetic tracing, researchers at Karolinska Institutet, the Medical University of Vienna in Austria and Harvard University in the USA have now identified and characterised all cell populations in mouse teeth and in the young growing and adult human teeth.

“From stem cells to the completely differentiated adult cells we were able to decipher the differentiation pathways of odontoblasts, which give rise to dentine – the hard tissue closest to the pulp – and ameloblasts, which give rise to the enamel.” said Igor Adameyko, Study Last Author, and Kaj Fried, Study Co-Author, Department of Neuroscience, Karolinska Institutet.

Source: https://www.news-medical.net/

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1,77 million years old tooth yields genetic material from extinct human species

April 11, 2020   DNA   No comments

Scientists have extracted from dental enamel the oldest human genetic material ever obtained, helping clarify the pivotal place in the human evolutionary lineage of a mysterious extinct species called Homo antecessor known from Spanish cave fossils. The researchers said they obtained genetic material from an 800,000-year-old Homo antecessor molar unearthed near the village of Atapuerca in northern Spain and from a 1.77 million-year-old molar of another extinct human species called Homo erectus found near the town of Dmanisi in Georgia. They retrieved the ancient proteins from fossilized teeth using a method called palaeoproteomics that can find genetic material in fossils too old to contain DNA because of its chemical degradation over time.

“Protein sequences are determined by the DNA sequence of our genomes, and therefore these ancient protein sequences provide some evolutionary information. We have previously shown we are able to extract ancient proteins even from 2 million year old animal fossils,” University of Copenhagen molecular anthropologist Frido Welker, lead author of the research published in the journal Nature, said on Monday.

Until now, the oldest genetic material from an extinct human species was dated to about 420,000 years ago.

Source: https://www.reuters.com/

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Scientists are Working on a Way to Regrow Teeth in 2 Months

March 20, 2020   DNA   No comments

It is scary to think about losing your teeth, especially if you are an adult, but it is an issue that a lot of people face. Around a quarter of adults lose their teeth by the age of 74.

Although there are dental implants that can help, they can be very uncomfortable, especially since they do not adapt to the mouth as it ages. However, a new technique might help people to grow new teeth in just 2 months by using the patient’s adult stem cells. The researchers from Columbia University Medical Center in New York City hope that they can get a patient’s stem cells to grow an anatomically correct tooth. Additionally, the new tooth will grow in a person’s empty socket, even allowing it to merge with the surrounding gum tissue. They have already proven the ability to grow the teeth, however, after months of research and experiments, it is not available for humans yet.

The researchers conducted an experiment using 22 rats, according to the Journal of Dental Research. After the growth factors were implanted in the mouths of the rats, new bone material regenerated and integrated within 2 months. According to the researchers of the study, this is the first time that teeth-like structures have been regenerated in a living organism.

There can be a lot of benefits that come along with the new procedure if this treatment proves successful in humans. Since the tooth is grown in the socket where it will stay, there is also no need to harvest outside stem cells or make an outside environment for the tooth as it grows.

Source: https://www.sciencetimes.com/

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Implants Without Risk Of Infection

December 21, 2019   DNA   No comments

Researchers at McMaster (Canada) have solved a vexing problem by engineering surface coatings that can repel everything, such as bacteria, viruses and living cells, but can be modified to permit beneficial exceptions. The discovery holds significant promise for medical and other applications, making it possible for implants such as vascular grafts, replacement heart valves and artificial joints to bond to the body without risk of infection or blood clotting. The new nanotechnology has the potential to greatly reduce false positives and negatives in medical tests by eliminating interference from non-target elements in blood and urine.

The research adds significant utility to completely repellent surfaces that have existed since 2011. Those surface coatings are useful for waterproofing phones and windshields, and repelling bacteria from food-preparation areas, for example, but have offered limited utility in medical applications where specific beneficial binding is required

 

“It was a huge achievement to have completely repellent surfaces, but to maximize the benefits of such surfaces, we needed to create a selective door that would allow beneficial elements to bond with those surfaces,” explains Tohid Didar of McMaster’s Department of Mechanical Engineering and School of Biomedical Engineering, the senior author of a paper that appears today in the journal ACS Nano.

In the case of a synthetic heart valve, for example, a repellent coating can prevent blood cells from sticking and forming clots, making it much safer.

“A coating that repels blood cells could potentially eliminate the need for medicines such as warfarin that are used after implants to cut the risk of clots,” says co-author , a McMaster PhD student in Biomedical Engineering. Still, she explains, a completely repellent coating also prevents the body from integrating the new valve into the tissue of the heart itself.

By designing the surface to permit adhesion only with heart tissue cells, the researchers are making it possible for the body to integrate the new valve naturally, avoiding the complications of rejection. The same would be true for other implants, such as artificial joints and stents used to open blood vessels.

“If you want a device to perform better and not be rejected by the body, this is what you need to do,” says co-author Maryam Badv, also a McMaster PhD student in Biomedical Engineering. “It is a huge problem in medicine.”

Source: https://brighterworld.mcmaster.ca/

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Alzheimer’s May Be Caused By Dental Infection

December 10, 2019   DNA   No comments

In a new study scientists reveal yet another reason to keep up on dental hygiene. Bacteria that cause a common yet largely preventable gum infection may also play a role in Alzheimer’s disease. The discovery also offers hope for a treatment that could slow neurodegeneration.

“There were many clues in the [features of Alzheimer’s disease] that an infection is at work,” said Casey Lynch, an entrepreneur and co-founder of Cortexyme, a biotech company headquartered at the Verily Life Sciences campus in South San Francisco, who led the new research. “Many of the genetic risk factors for Alzheimer’s are related to immune system function,” she added, which suggests “immune system dysfunction might put people more at risk.”

Alzheimer’s disease, an irreversible and progressive brain disorder that leads to memory loss and diminished thinking skills, affects at least 5 million Americans. Clumps of a brain protein known as amyloid plaques are a hallmark sign of the disease. Billions of research dollars have gone towards finding a treatment that destroys these mind-robbing masses. But there’s still no cure.

“Not enough people are asking what is upstream of the plaques … and [brain] inflammation,” said Lynch, who has a background in Alzheimer’s research and was frustrated by the string of failed therapies for the disease. Nearly six years ago, Lynch received a call from Stephen Dominy, a psychiatrist at the University of California, San Francisco, who had studied the link between HIVand dementia.

“I think I’ve found a bacterial cause of Alzheimer’s,” Dominy, who co-foundedCortexyme with Lynch and now serves as the company’s Chief Scientific Officer, told her. Dominy had spent about 15 years searching for infections that might lead to Alzheimer’s until evidence for a bacterium known as P. gingivalis became “undeniable,” according to Lynch. P. gingivalis causesperiodontitis, an infection that destroys the gums and can lead to tooth loss.

When the team examined the brains and cerebrospinal fluid of Alzheimer’spatients, they found DNA from the bacterium. They also discovered bacterial enzymes called gingipains that destroy brain cells were present, too. And when they watched P. gingivalis infections play out in mice, it triggered neurodegeneration in the hippocampus, a brain structure central to memory. It also led to Alzheimer’s hallmark amyloid beta plaqueproduction and inflammation, the researchers discovered.

The scientists then designed and created a new molecule that blocks the gingipain enzymes. The antibiotic reduced the amount of bacteria ininfected mice and stopped the formation of amyloid beta plaques whilereducing inflammation, the team reports Wednesday in the journal Science Advances.

Source: https://www.discovermagazine.com/

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New way to grow new teeth for patients

November 22, 2019   DNA   No comments


A group of histologists and dentists from School of Biomedicine, Far Eastern Federal University (FEFU), teamed up with Russian and Japanese colleagues and found cells that are probably responsible for the formation of human dental tissue. Researchers propose to apply the study outcome within the development of bioengineering techniques in dentistry aimed at growing new dental tissue for patients. A related article is published in the International Journal of Applied and Fundamental Research.

FEFU scientists used human prenatal tissues to study the early stage of development of the embryonic oral cavity during the period when the teeth were set up – from the 5th to the 6th week. They have recognized several types of cells that are involved in the formation of one of the teeth rudiments — the enamel (dental) organ. Among them, chromophobe cells with elongated spindle-shaped form have been identified which are also responsible for the development of human teeth in the first weeks of embryo formation. The data obtained can provide a fundamental basis for the development of bioengineering therapies in dentistry and gastroenterology.

‘Numerous attempts to grow teeth from only the stem cells involved in the development of enamel, dentin and pulp, i.e. ameloblasts and odontoblasts, were not successful: there was no enamel on the samples, teeth were covered only by defective dentin. The absence of an easily accessible source of cells for growing dental tissue seriously restricts the development of a bioengineering approach to dental treatment. To develop technologies of tissue engineering and regenerative medicine — promising methods of treatment in dentistry — the cells identified by us may become the clue to the new level of quality dental treatment. Natural implants that are completely identical to human teeth will no doubt be better than titanium ones, and their lifespan can be longer than that of artificial ones, which are guaranteed for 10-15 years. Although for a successful experiment, we still have a lack of knowledge about intercellular signaling interactions during the teeth development.‘ said Ivan Reva, Senior Researcher of the Laboratory for Cell and Molecular Neurobiology, School of Biomedicine, FEFU.

The scientist noted that large chromophobe cells reside not only the place where the teeth of the embryo form, but also exist at the border where the multilayers squamous epithelium of the oral cavity passes into the cylindrical epithelium of the developing digestive tube. This means that the new bio-engineering approach is relevant not only for growing new dental tissue but also for growing organs for subsequent transplantation and likely will be applied in gastroenterology.

Source: https://www.eurekalert.org/

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How To Print Crowns And Bridges, Surgical Guides For Dental Implant

November 22, 2019   DNA   No comments

Back at CES this year, we talked with 3D-printer maker Formlabs about its early experimentation in using its printers to make dentures faster and more affordably than existing alternatives. A few months later, the company is going deep on the concept. They’re releasing a 3D printer meant specifically for dental use, opening up a whole new wing called “Formlabs Dental” and acquiring their main resin supplier in order to better make materials for the dental industry.

Unfamiliar with Formlabs? The main thing to know is that their printers use Stereolithography (SLA) rather than the Fused Deposition Modeling (or FDM) that most people probably think of when it comes to 3D printing; in other words, they use carefully aimed UV lasers to precisely harden an otherwise goopy resin into whatever you want to print, whereas FDM printers heat up a solid material until it’s malleable and then push it through a hot glue gun-style nozzle to build a model layer by layer. SLA tends to offer higher accuracy and resolution, whereas FDM tends to be cheaper and offer a wider variety of colors and material properties.

Formlabs calls its new dentistry-centric printer the “Form 3b” — which, as the name suggests, is a slight variation on the Form 3 printer the company introduced earlier this year. The base package costs about a thousand bucks more per unit over the non-dental Form 3, but comes with software meant to tie into a dental team’s existing workflow, along with a year of Formlab’s “Dental Service Plan,” which includes training, support and the ability to request a new printer if something needs repairing (rather than waiting for yours to get shipped back and forth). The company also says the 3b has been optimized to work with its dental resins, but doesn’t say much about how.

Speaking of resins: Formlabs is acquiring Spectra, which has been its primary supplier of resins since Formlabs started back in 2012. While the company isn’t disclosing any of the terms of the deal, it does say it has put over a million dollars into building an FDA-registered clean room to make medical-grade resins. Formlabs says that anyone who already buys materials and resin from Spectra can continue to do so.

The company’s new “Formlabs Dental” division, meanwhile, will focus on figuring out new dental materials and ways to better tie in to existing dentist office workflows. Right now, the company says, the Form 3b can be used to print crowns and bridges, clear retainers, surgical guides to help during dental implant procedures, custom mouth guards (or “occlusal splints”) and dentures.

Source: https://formlabs.com/
AND
https://techcrunch.com/

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Bone Tissue Just Needs A Little Bit Of Encouragement To Regenerate

November 22, 2019   DNA   No comments

Regrowing bones is no easy task, but the world’s lightest solid might make it easier to achieve. Researchers have figured out a way to use hybrid aerogels, strong but ultralight materials, to prompt new bone tissue to grow and replace lost or damaged tissue. Although bone cancer is a relatively rare disease (it accounts for less than 1% of all cancers), people who suffer from it often end up losing a lot of bone tissue and in extreme cases, undergo amputation. The cancerous tissue has to be cut out, taking with it a large chunk of nearby healthy tissue to make sure that the cancer does not spread. This effectively removes the cancer, but also leaves the patient with a lot less bone than they started out with.

A recent study has used hybrid aerogels to restore the lost tissue by prompting bone regeneration. Aerogels are basically a combination of solid and gas. Think Jell-O, but one where the water has been slowly dried out and replaced completely by air. This slow and careful removing of liquid is what allows the gel to retain its shape instead of shriveling into a hard lump. The pairing of solid and gas makes aerogels extremely light and very porous. These two qualities make them exceptionally suitable to use as scaffolds, which can be used as physical roadmaps for the developing bone to follow as it grows.

A section of bone with osteosarcoma, a type of bone cancer. This is one of the cases where lost tissue could be restored by prompting bone regeneration.

Currently, the most common methods of bone regeneration either graft new bone on to the repair site or slowly pull two bits of bone further and further apart to allow new bone to grow in the gap. If you think that these methods sound painful, complicated, and expensive, you are right.

It turns out that bone tissue just needs a little bit of encouragement to regenerate. Most of the time, simple mechanical pressure will do the trick. The fiddly bit is getting the new bone tissue to grow in the right direction and for the right amount of time. Stop it too early and the bone will be too weak to actually serve a purpose. Let it grow too much and it will end up as painful projections. This balanced growth can be achieved by using a scaffold, which is where hybrid aerogels come in. A scaffold is a structure that is placed at the site of bone repair, where it guides the growing tissue along its destined path. A good scaffold is strong but not too stiff, lasts just long enough for fresh tissue to develop, and has a lot of pores for the growing bone to snake through. This last bit is what makes a scaffold very similar to real bone. Hybrid aerogels happen to be a magic material that hits all these notes.

There are a lot of different kinds of scaffolds to choose from, ranging from ceramic and metals to cellulose hydrogels. So what makes hybrid aerogels any better than other scaffolds? For one, they are half made of proteins (that’s the “hybrid” bit), which are eventually broken down by the body. The other half, silica, slowly melts away as orthosilicic acid, which is known to hasten wound healing. Their pore size can be controlled during the manufacturing process, making it easy to adapt them to different uses. They are also being tested as drug delivery systems, meaning that the material could be spiked with medicines or growth factors before using it as a scaffold.

Earlier this year, three research labs based out of Iran, Germany, and Austria got together and decided to fuse a very strong protein with a very light and porous aerogel. The very strong protein is silk fibroin, the stuff found in silkworm cocoons and used to make fancy fabrics. It makes the aerogel strong and just stiff enough to use for bone growth. With the raw materials ready, the scientists started with Phase I: make the hybrid aerogel. Throw a source of silica, silk fibroin, some acid and a touch of detergent into a pot. Bake for an hour and voilà! You have yourself a silica-silk fibroin hybrid aerogel.

 Hybrid aerogels are strong but ultralight materials. Here, the flower is protected from the fire by the insulating properties of the aerogel
The researchers made the perfect hybrid aerogel – hydrophilic (water-loving), not too stiff, and adequately biodegradable.

Having made the material, they now moved to Phase II: check if the hybrid aerogels are in any way harmful to human cells. In fact, the cells seemed to really like the material. When the hybrid aerogel was placed in a dish containing bone cells, they readily grew on its surface, depositing the proteins and minerals required for bone growth along the way.

On to Phase III: implant the hybrid aerogel in mice and check if it stimulates bone regeneration. The researchers made small bone injuries in two groups of mice and implanted the hybrid aerogel in one of them. After 25 days, they saw that the mice with the implants showed faster and better healing than the mice without implants. The aerogel was not just allowing new bone to grow, but also making it grow faster than normal.

This ability of the hybrid aerogel to speed up bone regeneration places it on the forefront of new therapeutic technologies. Imagine having bone fractures healing in a span of days, as opposed to weeks. Or being able to tell a bone cancer patient that, “Yes, you have to cut out a section of their leg but it can be easily grown back, no worries.” Hybrid aerogels are possibly the biomaterial that could make such conversations a reality.

Source: https://massivesci.com/

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How A Common Oral Bacteria Makes Colon Cancer More Deadly

September 20, 2019   DNA   No comments

Researchers at the Columbia University College of Dental Medicine have determined how F. nucleatum — a common oral bacteria often implicated in tooth decay — accelerates the growth of colon cancer. The study was published online in the journal EMBO Reports. The findings could make it easier to identify and treat more aggressive colon cancers. It also helps explain why some cases advance far more quickly than others, thanks to the same bacteria found in dental plaque.

Colon cancer is the second leading cause of cancer death in the U.S. Researchers have long known that the disease is caused by genetic mutations that typically accumulate over the course of a decade.

Images of noncancerous (far left) versus cancerous colorectal tissue (middle and right) from the same patient who was infected with F. nucleatum. Red indicates the FadA adhesin, a protein that is produced by the bacterium and accelerates cancerous tumor growth. Green indicates Annexin A1, a protein released in increasing amounts by cancerous tissue when infected with F. nucleatum.

“Mutations are just part of the story,” says study leader Yiping W. Han, PhD, professor of microbial sciences at Columbia University’s College of Dental Medicine and Vagelos College of Physicians & Surgeons. “Other factors, including microbes, can also play a role.”

Scientists have also demonstrated that about a third of colorectal cancers are associated with a common oral bacterium called F. nucleatum. Those cases are often the most aggressive, but nobody knew why. In a prior study, Han’s research team discovered that the bacterium makes a molecule called FadA adhesin, triggering a signaling pathway in colon cells that has been implicated in several cancers. They also found that FadA adhesin only stimulates the growth of cancerous cells, not healthy cells.  “We needed to find out why F. nucleatum only seemed to interact with the cancerous cells,” says Han.

Source: https://www.dental.columbia.edu/

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