Category Archives: nanotechnology

mRNA, COVID-19 vaccines, treating genetic diseases before birth, and the scientist who started it all

This post was going to be about new research into fetal therapeutics and mRNA.But, since I’ve been very intrigued by the therapeutic agent, mRNA, which has been a big part of the COVID-19 vaccine story; this seemed like a good opportunity to dive a little more deeply into that topic at the same time.

It’s called messenger ribonucleic acid (mRNA) and until seeing this video I had only the foggiest idea of how it works, which is troubling since at least two COVID-19 vaccines are based on this ‘new’ technology. From a November 10, 2020 article by Damian Garde for STAT,

Garde’s article offers detail about mRNA along with fascinating insight into how science and entreneurship works.

mRNA—it’s in the details, plus, the loneliness of pioneer researchers, a demotion, and squabbles

Garde’s November 10, 2020 article provides some explanation about how mRNA vaccines work and it takes a look at what can happen to pioneering scientists (Note: A link has been removed),

For decades, scientists have dreamed about the seemingly endless possibilities of custom-made messenger RNA, or mRNA.

Researchers understood its role as a recipe book for the body’s trillions of cells, but their efforts to expand the menu have come in fits and starts. The concept: By making precise tweaks to synthetic mRNA and injecting people with it, any cell in the body could be transformed into an on-demand drug factory. [emphasis mine]

But turning scientific promise into medical reality has been more difficult than many assumed. Although relatively easy and quick to produce compared to traditional vaccine-making, no mRNA vaccine or drug has ever won approval [until 2021].

Whether mRNA vaccines succeed or not, their path from a gleam in a scientist’s eye to the brink of government approval has been a tale of personal perseverance, eureka moments in the lab, soaring expectations — and an unprecedented flow of cash into the biotech industry.

Before messenger RNA was a multibillion-dollar idea, it was a scientific backwater. And for the Hungarian-born scientist behind a key mRNA discovery, it was a career dead-end.

Katalin Karikó spent the 1990s collecting rejections. Her work, attempting to harness the power of mRNA to fight disease, was too far-fetched for government grants, corporate funding, and even support from her own colleagues.

It all made sense on paper. In the natural world, the body relies on millions of tiny proteins to keep itself alive and healthy, and it uses mRNA to tell cells which proteins to make. If you could design your own mRNA, you could, in theory, hijack that process and create any protein you might desire — antibodies to vaccinate against infection, enzymes to reverse a rare disease, or growth agents to mend damaged heart tissue.

In 1990, researchers at the University of Wisconsin managed to make it work in mice. Karikó wanted to go further.

The problem, she knew, was that synthetic RNA was notoriously vulnerable to the body’s natural defenses, meaning it would likely be destroyed before reaching its target cells. And, worse, the resulting biological havoc might stir up an immune response that could make the therapy a health risk for some patients.

It was a real obstacle, and still may be, but Karikó was convinced it was one she could work around. Few shared her confidence.

“Every night I was working: grant, grant, grant,” Karikó remembered, referring to her efforts to obtain funding. “And it came back always no, no, no.”

By 1995, after six years on the faculty at the University of Pennsylvania, Karikó got demoted. She had been on the path to full professorship, but with no money coming in to support her work on mRNA, her bosses saw no point in pressing on.

She was back to the lower rungs of the scientific academy.

“Usually, at that point, people just say goodbye and leave because it’s so horrible,” Karikó said.

There’s no opportune time for demotion, but 1995 had already been uncommonly difficult. Karikó had recently endured a cancer scare, and her husband was stuck in Hungary sorting out a visa issue. Now the work to which she’d devoted countless hours was slipping through her fingers.

“I thought of going somewhere else, or doing something else,” Karikó said. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”

In time, those better experiments came together. After a decade of trial and error, Karikó and her longtime collaborator at Penn — Drew Weissman, an immunologist with a medical degree and Ph.D. from Boston University — discovered a remedy for mRNA’s Achilles’ heel.

The stumbling block, as Karikó’s many grant rejections pointed out, was that injecting synthetic mRNA typically led to that vexing immune response; the body sensed a chemical intruder, and went to war. The solution, Karikó and Weissman discovered, was the biological equivalent of swapping out a tire.

Every strand of mRNA is made up of four molecular building blocks called nucleosides. But in its altered, synthetic form, one of those building blocks, like a misaligned wheel on a car, was throwing everything off by signaling the immune system. So Karikó and Weissman simply subbed it out for a slightly tweaked version, creating a hybrid mRNA that could sneak its way into cells without alerting the body’s defenses.

“That was a key discovery,” said Norbert Pardi, an assistant professor of medicine at Penn and frequent collaborator. “Karikó and Weissman figured out that if you incorporate modified nucleosides into mRNA, you can kill two birds with one stone.”

That discovery, described in a series of scientific papers starting in 2005, largely flew under the radar at first, said Weissman, but it offered absolution to the mRNA researchers who had kept the faith during the technology’s lean years. And it was the starter pistol for the vaccine sprint to come.

Entrepreneurs rush in

Garde’s November 10, 2020 article shifts focus from Karikó, Weissman, and specifics about mRNA to the beginnings of what might be called an entrepreneurial gold rush although it starts sedately,

Derrick Rossi [emphasis mine], a native of Toronto who rooted for the Maple Leafs and sported a soul patch, was a 39-year-old postdoctoral fellow in stem cell biology at Stanford University in 2005 when he read the first paper. Not only did he recognize it as groundbreaking, he now says Karikó and Weissman deserve the Nobel Prize in chemistry.

“If anyone asks me whom to vote for some day down the line, I would put them front and center,” he said. “That fundamental discovery is going to go into medicines that help the world.”

But Rossi didn’t have vaccines on his mind when he set out to build on their findings in 2007 as a new assistant professor at Harvard Medical School running his own lab.

He wondered whether modified messenger RNA might hold the key to obtaining something else researchers desperately wanted: a new source of embryonic stem cells [emphasis mine].

In a feat of biological alchemy, embryonic stem cells can turn into any type of cell in the body. That gives them the potential to treat a dizzying array of conditions, from Parkinson’s disease to spinal cord injuries.

But using those cells for research had created an ethical firestorm because they are harvested from discarded embryos.

Rossi thought he might be able to sidestep the controversy. He would use modified messenger molecules to reprogram adult cells so that they acted like embryonic stem cells.

He asked a postdoctoral fellow in his lab to explore the idea. In 2009, after more than a year of work, the postdoc waved Rossi over to a microscope. Rossi peered through the lens and saw something extraordinary: a plate full of the very cells he had hoped to create.

Rossi excitedly informed his colleague Timothy Springer, another professor at Harvard Medical School and a biotech entrepreneur. Recognizing the commercial potential, Springer contacted Robert Langer, the prolific inventor and biomedical engineering professor at the Massachusetts Institute of Technology.

On a May afternoon in 2010, Rossi and Springer visited Langer at his laboratory in Cambridge. What happened at the two-hour meeting and in the days that followed has become the stuff of legend — and an ego-bruising squabble.

Langer is a towering figure in biotechnology and an expert on drug-delivery technology. At least 400 drug and medical device companies have licensed his patents. His office walls display many of his 250 major awards, including the Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers.

As he listened to Rossi describe his use of modified mRNA, Langer recalled, he realized the young professor had discovered something far bigger than a novel way to create stem cells. Cloaking mRNA so it could slip into cells to produce proteins had a staggering number of applications, Langer thought, and might even save millions of lives.

“I think you can do a lot better than that,” Langer recalled telling Rossi, referring to stem cells. “I think you could make new drugs, new vaccines — everything.”

Within several months, Rossi, Langer, Afeyan [Noubar Afeyan, venture capitalist, founded and runs Flagship Ventures], and another physician-researcher at Harvard formed the firm Moderna — a new word combining modified and RNA.

Springer was the first investor to pledge money, Rossi said. In a 2012 Moderna news release, Afeyan said the firm’s “promise rivals that of the earliest biotechnology companies over 30 years ago — adding an entirely new drug category to the pharmaceutical arsenal.”

But although Moderna has made each of the founders hundreds of millions of dollars — even before the company had produced a single product — Rossi’s account is marked by bitterness. In interviews with the [Boston] Globe in October [2020], he accused Langer and Afeyan of propagating a condescending myth that he didn’t understand his discovery’s full potential until they pointed it out to him.

Garde goes on to explain how BioNTech came into the mRNA picture and contrasts the two companies’ approaches to biotechnology as a business. It seems BioNTech has not cashed in the same way as has Moderna. (For some insight into who’s making money from COVID-19 check out Giacomo Tognini’s December 23, 2020 article (Meet The 50 Doctors, Scientists And Healthcare Entrepreneurs Who Became Pandemic Billionaires In 2020) for Forbes.)

Garde ends his November 10, 2020 article on a mildly cautionary note,

“You have all these odd clinical and pathological changes caused by this novel bat coronavirus [emphasis mine], and you’re about to meet it with all of these vaccines with which you have no experience,” said Paul Offit, an infectious disease expert at Children’s Hospital of Philadelphia and an authority on vaccines.

What happened to Katalin Karikó?

Matthew Rosza’s January 25, 2021 article about Karikó and her pioneering work features an answer to my question and some advice,

“I want young people to feel — if my example, because I was demoted, rejected, terminated, I was even subject for deportation one point — [that] if they just pursue their thing, my example helps them to wear rejection as a badge,” Karikó, who today is a senior vice president at BioNTech RNA Pharmaceuticals, told Salon last month when discussing her story. “‘Okay, well, I was rejected. I know. Katalin was rejected and still [succeeded] at the end.’ So if it helps them, then it helps them.”

Despite her demotion, Karikó continued with her work and, along with a fellow immunologist named Dr. Drew Weissman, penned a series of influential articles starting in 2005. These articles argued that mRNA vaccines would not be neutralized by the human immune system as long as there were specific modifications to nucleosides, a compound commonly found in RNA.

By 2013, Karikó’s work had sufficiently impressed experts that she left the University of Pennsylvania for BioNTech RNA Pharmaceuticals.

Karikó tells Salon that the experience taught her one important lesson: In life there will be people who, for various reasons, will try to hold you back, and you can’t let them get you down.

“People that are in power, they can help you or block you,” Karikó told Salon. “And sometimes people select to make your life miserable. And now they cannot be happy with me because now they know that, ‘Oh, you know, we had the confrontation and…’ But I don’t spend too much time on these things.”

Before moving onto the genetic research which prompted this posting, I have an answer to the following questions:

Could an mRNA vaccine affect your DNA (deoxyribonucleic acid) and how do mRNA vaccines differ from the traditional ones?

No, DNA is not affected by the COVID-19 mRNA vaccines, according to a January 5, 2021 article by Jason Murdock for Newsweek,

The type of vaccines used against COVID-19 do not interact with or alter human genetic code, also known as DNA, scientists say.

In traditional vaccines, a piece of a virus, known as an “antigen,” would be injected into the body to force the immune system to make antibodies to fight off future infection. But mRNA-based methods do not use a live virus, and cannot give someone COVID.

Instead, mRNA vaccines give cells the instructions to make a “spike” protein also found on the surface of the virus that causes COVID. The body kickstarts its immune response by creating the antibodies needed to combat those specific virus proteins.

Once the spike protein is created, the cell breaks down the instructions provided by the mRNA molecule, leaving the human immune system prepared to combat infection. The mRNA vaccines are not a medicine—nor a cure—but a preventative measure.

Gavi, a vaccine alliance partnered with the World Health Organization (WHO), has said that mRNA instructions will become degraded in approximately 72 hours.

It says mRNA strands are “chemical intermediaries” between DNA in our chromosomes and the “cellular machinery that produces the proteins we need to function.”

But crucially, while mRNA vaccines will give the human body the blueprints on how to assemble proteins, the alliance said in a fact-sheet last month that “mRNA isn’t the same as DNA, and it can’t combine with our DNA to change our genetic code.”

It explained: “Some viruses like HIV can integrate their genetic material into the DNA of their hosts, but this isn’t true of all viruses… mRNA vaccines don’t carry these enzymes, so there is no risk of the genetic material they contain altering our DNA.”

The [US] Centers for Disease Control and Prevention (CDC) says on its website that mRNA vaccines that are rolling out don’t “interact with our DNA in any way,” and “mRNA never enters the nucleus of the cell, which is where our DNA (genetic material) is kept.”

Therapeutic fetal mRNA treatment

Rossi’s work on mRNA and embryonic stem cells bears a relationship of sorts to this work focusing on prebirth therapeutics. (From a January 13, 2021 news item on Nanowerk), Note: A link has been removed,

Researchers at Children’s Hospital of Philadelphia and the School of Engineering and Applied Science at the University of Pennsylvania have identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy.

The proof-of-concept study, published in Science Advances (“Ionizable Lipid Nanoparticles for In Utero mRNA Delivery”), engineered and screened a number of lipid nanoparticle formulations for targeting mouse fetal organs and has laid the groundwork for testing potential therapies to treat genetic diseases before birth.

A January 13, 2021 Children’s Hospital of Philadelphia (CHOP) news release (also on EurekAlert), which originated the news item, delves further into the research,

“This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth,” said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. “These lipid nanoparticles may provide a platform for in utero mRNA delivery, which would be used in therapies like fetal protein replacement and gene editing.”

Recent advances in DNA sequencing technology and prenatal diagnostics have made it possible to diagnose many genetic diseases before birth. Some of these diseases are treated by protein or enzyme replacement therapies after birth, but by then, some of the damaging effects of the disease have taken hold. Thus, applying therapies while the patient is still in the womb has the potential to be more effective for some conditions. The small fetal size allows for maximal therapeutic dosing, and the immature fetal immune system may be more tolerant of replacement therapy.

Of the potential vehicles for introducing therapeutic protein replacement, mRNA is distinct from other nucleic acids, such as DNA, because it does not need to enter the nucleus and can use the body’s own machinery to produce the desired proteins. Currently, the common methods of nucleic acid delivery include viral vectors and nonviral approaches. Although viral vectors may be well-suited to gene therapy, they come with the potential risk of unwanted integration of the transgene or parts of the viral vector in the recipient genome. Thus, there is an important need to develop safe and effective nonviral nucleic acid delivery technologies to treat prenatal diseases.

In order to identify potential nonviral delivery systems for therapeutic mRNA, the researchers engineered a library of lipid nanoparticles, small particles less than 100 nanometers in size that effectively enter cells in mouse fetal recipients. Each lipid nanoparticle formulation was used to encapsulate mRNA, which was administered to mouse fetuses. The researchers found that several of the lipid nanoparticles enabled functional mRNA delivery to fetal livers and that some of those lipid nanoparticles also delivered mRNA to the fetal lungs and intestines. They also assessed the lipid nanoparticles for toxicity and found them to be as safe or safer than existing formulations.

Having identified the lipid nanoparticles that were able to accumulate within fetal livers, lungs, and intestines with the highest efficiency and safety, the researchers also tested therapeutic potential of those designs by using them to deliver erythropoietin (EPO) mRNA, as the EPO protein is easily trackable. They found that EPO mRNA delivery to liver cells in mouse fetuses resulted in elevated levels of EPO protein in the fetal circulation, providing a model for protein replacement therapy via the liver using these lipid nanoparticles.

“A central challenge in the field of gene therapy is the delivery of nucleic acids to target cells and tissues, without causing side effects in healthy tissue. This is difficult to achieve in adult animals and humans, which have been studied extensively. Much less is known in terms of what is required to achieve in utero nucleic acid delivery,” said Mitchell. “We are very excited by the initial results of our lipid nanoparticle technology to deliver mRNA in utero in safe and effective manner, which could open new avenues for lipid nanoparticles and mRNA therapeutics to treat diseases before birth.”

Here’s a link to and a citation for the paper,

Ionizable lipid nanoparticles for in utero mRNA delivery by Rachel S. Riley, Meghana V. Kashyap, Margaret M. Billingsley, Brandon White, Mohamad-Gabriel Alameh, Sourav K. Bose, Philip W. Zoltick, Hiaying Li, Rui Zhang, Andrew Y. Cheng, Drew Weissman, William H. Peranteau, Michael J. Mitchell. Science Advances 13 Jan 2021: Vol. 7, no. 3, eaba1028 DOI: 10.1126/sciadv.aba1028

This paper appears to be open access. BTW, I noticed Drew Weissman’s name as one of the paper’s authors and remembered him as one of the first to recognize Karikó’s pioneering work. I imagine that when he co-authored papers with Karikó he was risking his reputation.

Funny how a despised field of research has sparked a ‘gold rush’ for research and for riches, yes?.

Printing paper loudspeakers

When I was working on my undergraduate communications degree, we spent a fair chunk of time discussing the printed word; this introduction (below in the excerpt) brings back memories. I am going to start with an excerpt from the study (link and citation to follow at the end of this post) before moving on to the news item and press release. It’s a good introduction (Note Links have been removed),

For a long time, paper has been used as storing medium for written information only [emphasis mine]. In combination with the development of printing technologies, it became one of the most relevant materials as information could be reproduced multiple times and brought to millions of people in a simple, cheap, and fast way. However, with the digital revolution the end of paper has been forecasted.

However, paper still has its big advantages. The yearly production is still huge with over 400 million tons worldwide[1] for a wide application range going much beyond conventional books, newspapers, packages, or sanitary products. It is a natural light‐weight, flexible, recyclable, multi‐functional material making it an ideal candidate as part of novel electronic devices, especially based on printed electronics.[2] During the last decade, a wide variety of electronic functionalities have been demonstrated with paper as the common substrate platform. It has been used as basis for organic circuits,[3] microwave and digital electronics,[4] sensors,[5-7] actuators,[8, 9] and many more.

My first posting about this work from Chemnitz University of Technology with paper, loudspeakers, and printed electronics was a May 4, 2012 posting.

Enough of that trip down memory lane, a January 26, 2021 news item on Nanowerk announces research into printing loudspeakers onto roll-to-roll printed paper,

If the Institute for Print and Media Technology at Chemnitz University of Technology [Germany] has its way, many loudspeakers of the future will not only be as thin as paper, but will also sound impressive. This is a reality in the laboratories of the Chemnitz researchers, who back in 2015 developed the multiple award-winning T-Book – a large-format illustrated book equipped with printed electronics. If you turn a page, it begins to sound through a speaker invisibly located inside the sheet of paper.

“The T-Book was and is a milestone in the development of printed electronics, but development is continuing all the time,” says Prof. Dr. Arved C. Hübler, under whose leadership this technology trend, which is becoming increasingly important worldwide, has been driven forward for more than 20 years.

A January 26, 2021 Chemnitz University of Technology press release by Mario Steinebach/Translator: Chelsea Burris, which originated the news item, delves further into the topic,

From single-sheet production to roll-to-roll printing

Five years ago, the sonorous paper loudspeakers from Chemnitz were still manufactured in a semi-automatic single-sheet production process. In this process, ordinary paper or foils are printed with two layers of a conductive organic polymer as electrodes. A piezoelectric layer is sandwiched between them as the active element, which causes the paper or film to vibrate. Loud and clear sound is produced by air displacement. The two sides of the speaker paper can be printed in color. Since this was only possible in individual sheets in limited formats, the efficiency of this relatively slow manufacturing process is very low. That’s why researchers at the Institute of Print and Media Technology have been looking for a new way towards cost-effective mass production since May 2017.

The aim of their latest project, roll-to-roll printed speaker paper (T-Paper for short), was therefore to convert sheet production into roll production. “Researchers from the fields of print media technology, chemistry, physics, acoustics, electrical engineering, and economics from six nations developed a continuous, highly productive, and reliable roll production of loudspeaker webs,” reports project manager Georg C. Schmidt. Not only did they use the roll-to-roll (R2R) printing process for this, but they also developed inline technologies for other process steps, such as the lamination of functional layers. “This allows electronics to be embedded in the paper – invisibly and protected,” says Hübler. In addition, he says, inline polarization of piezoelectric polymer layers has been achieved for the first time and complete inline process monitoring of the printed functional layers is possible. The final project results were published in the renowned journal Advanced Materials in January 2021.

Long and lightweight paper loudspeaker webs for museums, the advertising industry, and Industry 4.0

The potential of loudspeaker paper was extended to other areas of application in the T-Paper project. For example, meter-long loudspeaker installations can now be manufactured in web form or as a circle (T-RING). “In our T-RING prototype, an almost four-meter-long track with 56 individual loudspeakers was connected to form seven segments and shaped into a circle, making a 360° surround sound installation possible,” says Schmidt. The speaker track, including printed circuitry, weighs just 150 grams and consists of 90 percent conventional paper that can be printed in color on both sides. “This means that low-cost infotainment solutions are now possible in museums, at trade shows and in the advertising industry, for example. In public buildings, for example, very homogeneous sound reinforcement of long stretches such as corridors is possible. But the process technology itself could also become interesting for other areas, such as the production of inline measurement systems for Industry 4.0,” says the project manager, looking to the future.

The T-Paper project was funded by the Federal Ministry of Education and Research from 2017 to 2020 with 1.37 million euros as part of the Validation of the technological and societal innovation potential of scientific research – VIP+ funding measure.

Here’s a link to and a citation for the paper,

Paper‐Embedded Roll‐to‐Roll Mass Printed Piezoelectric Transducers by Georg C. Schmidt, Pramul M. Panicker, Xunlin Qiu, Aravindan J. Benjamin, Ricardo A. Quintana Soler, Issac Wils, Arved C. Hübler. Advanced Materials DOI: https://doi.org/10.1002/adma.202006437 First published: 18 January 2021

This paper is open access.

For anyone curious about the T-Paper project, you can find it here.

Graphene-based material for high-performance supercapacitors

Researchers from Russia and France have developed a new material, based on graphene, that would allow supercapacitors to store more energy according to a January 15, 2021 news item on Nanowerk,

Scientists of Tomsk Polytechnic University jointly with colleagues from the University of Lille (Lille, France) synthetized a new material based on reduced graphene oxide (rGO) for supercapacitors, energy storage devices. The rGO modification method with the use of organic molecules, derivatives of hypervalent iodine, allowed obtaining a material that stores 1.7 times more electrical energy.

Photo: modified rGO supercapacitor electrodes. Courtesy: Tomsk University

A January 15, 2020 Tomsk Polytechnic University press release (also on EurekAlert), which originated the news item, provides more details,

A supercapacitor is an electrochemical device for storage and release of electric charge. Unlike batteries, they store and release energy several times faster and do not contain lithium.

A supercapacitor is an element with two electrodes separated by an organic or inorganic electrolyte. The electrodes are coated with an electric charge accumulating material. The modern trend in science is to use various materials based on graphene, one of the thinnest and most durable materials known to man. The researchers of TPU and the University of Lille used reduced graphene oxide (rGO), a cheap and available material.

“Despite their potential, supercapacitors are not wide-spread yet. For further development of the technology, it is required to enhance the efficiency of supercapacitors. One of the key challenges here is to increase the energy capacity.

It can be achieved by expanding the surface area of an energy storage material, rGO in this particular case. We found a simple and quite fast method. We used exceptionally organic molecules under mild conditions and did not use expensive and toxic metals,” Pavel Postnikov, Associate Professor of TPU Research School of Chemistry and Applied Biomedical Science and the research supervisor says.

Reduced graphene oxide in a powder form is deposited on electrodes. As a result, the electrode becomes coated with hundreds of nanoscale layers of the substance. The layers tend to agglomerate, in other words, to sinter. To expand the surface area of a material, the interlayer spacing should be increased.

“For this purpose, we modified rGO with organic molecules, which resulted in the interlayer spacing increase. Insignificant differences in interlayer spacing allowed increasing energy capacity of the material by 1.7 times. That is, 1 g of the new material can store 1.7 times more energy in comparison with a pristine reduced graphene oxide,” Elizaveta Sviridova, Junior Research Fellow of TPU Research School of Chemistry and Applied Biomedical Sciences and one of the authors of the article explains.

The reaction proceeded through the formation of active arynes from iodonium salts. They kindle scientists` interest due to their property to form a single layer of new organic groups on material surfaces. The TPU researchers have been developing the chemistry of iodonium salts for many years.

“The modification reaction proceeds under mild conditions by simply mixing the solution of iodonium salt with reduced graphene oxide. If we compare it with other methods of reduced graphene oxide functionalization, we have achieved the highest indicators of material energy capacity increase,” Elizaveta Sviridova says.

Here’s a link to and a citation for the paper,

Aryne cycloaddition reaction as a facile and mild modification method for design of electrode materials for high-performance symmetric supercapacitor by Elizaveta Sviridova, Min Li, Alexandre Barras, Ahmed Addad, Mekhman S.Yusubov, Viktor V. Zhdankin, Akira Yoshimura, Sabine Szunerits, Pavel S. Postnikov, Rabah Boukherroub. Electrochimica Acta Volume 369, 10 February 2021, 137667 DOI: https://doi.org/10.1016/j.electacta.2020.137667

This paper is behind a paywall.

CRISPR technology is like a pair of scissors and a dimmer switch?

The ‘pair of scissors’ analogy is probably the most well known of the attempts to describe how the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 gene editing system works. It seems a new analogy is about to be added according to a January 19 2021 news item on ScienceDaily (Note: This October 30, 2019 posting features more CRISPR analogies),

In a series of experiments with laboratory-cultured bacteria, Johns Hopkins scientists have found evidence that there is a second role for the widely used gene-cutting system CRISPR-Cas9 — as a genetic dimmer switch for CRISPR-Cas9 genes. Its role of dialing down or dimming CRISPR-Cas9 activity may help scientists develop new ways to genetically engineer cells for research purposes.

Here’s an image illustrating the long form of the tracrRNA or ‘dimmer switch’ alongside the more commonly used short form,

Caption: Left – a schematic of the long form of the tracrRNA used by the CRISPR-Cas9 system in bacteria; Right – the standard guide RNA used by many scientists as part of the gene-cutting CRISPR-Cas9 system. Credit: Joshua Modell, Rachael Workman and Johns Hopkins Medicine

A January 19 ,2021 Johns Hopkins Medicine news release (also on EurekAlert), which originated the news item, explains about CRISPR and what the acronym stands for, as well as, giving more details about the discovery,

First identified in the genome of gut bacteria in 1987, CRISPR-Cas9 is a naturally occurring but unusual group of genes with a potential for cutting DNA sequences in other types of cells that was realized 25 years later. Its value in genetic engineering — programmable gene alteration in living cells, including human cells — was rapidly appreciated, and its widespread use as a genome “editor” in thousands of laboratories worldwide was recognized in the awarding of the Nobel Prize in Chemistry last year to its American and French co-developers.

CRISPR stands for clustered, regularly interspaced short palindromic repeats. Cas9, which refers to CRISPR-associated protein 9, is the name of the enzyme that makes the DNA slice. Bacteria naturally use CRISPR-Cas9 to cut viral or other potentially harmful DNA and disable the threat, says Joshua Modell, Ph.D., assistant professor of molecular biology and genetics at the Johns Hopkins University School of Medicine. In this role, Modell says, “CRISPR is not only an immune system, it’s an adaptive immune system — one that can remember threats it has previously encountered by holding onto a short piece of their DNA, which is akin to a mug shot.” These mug shots are then copied into “guide RNAs” that tell Cas9 what to cut.

Scientists have long worked to unravel the precise steps of CRISPR-Cas9’s mechanism and how its activity in bacteria is dialed up or down. Looking for genes that ignite or inhibit the CRISPR-Cas9 gene-cutting system for the common, strep-throat causing bacterium Streptococcus pyogenes, the Johns Hopkins scientists found a clue regarding how that aspect of the system works.

Specifically, the scientists found a gene in the CRISPR-Cas9 system that, when deactivated, led to a dramatic increase in the activity of the system in bacteria. The product of this gene appeared to re-program Cas9 to act as a brake, rather than as a “scissor,” to dial down the CRISPR system.

“From an immunity perspective, bacteria need to ramp up CRISPR-Cas9 activity to identify and rid the cell of threats, but they also need to dial it down to avoid autoimmunity — when the immune system mistakenly attacks components of the bacteria themselves,” says graduate student Rachael Workman, a bacteriologist working in Modell’s laboratory.

To further nail down the particulars of the “brake,” the team’s next step was to better understand the product of the deactivated gene (tracrRNA). RNA is a genetic cousin to DNA and is vital to carrying out DNA “instructions” for making proteins. TracrRNAs belong to a unique family of RNAs that do not make proteins. Instead, they act as a kind of scaffold that allows the Cas9 enzyme to carry the guide RNA that contains the mug shot and cut matching DNA sequences in invading viruses.

TracrRNA comes in two sizes: long and short. Most of the modern gene-cutting CRISPR-Cas9 tools use the short form. However, the research team found that the deactivated gene product was the long form of tracrRNA, the function of which has been entirely unknown.

The long and short forms of tracrRNA are similar in structure and have in common the ability to bind to Cas9. The short form tracrRNA also binds to the guide RNA. However, the long form tracrRNA doesn’t need to bind to the guide RNA, because it contains a segment that mimics the guide RNA. “Essentially, long form tracrRNAs have combined the function of the short form tracrRNA and guide RNA,” says Modell.

In addition, the researchers found that while guide RNAs normally seek out viral DNA sequences, long form tracrRNAs target the CRISPR-Cas9 system itself. The long form tracrRNA tends to sit on DNA, rather than cut it. When this happens in a particular area of a gene, it prevents that gene from expressing, — or becoming functional.

To confirm this, the researchers used genetic engineering to alter the length of a certain region in long form tracrRNA to make the tracrRNA appear more like a guide RNA. They found that with the altered long form tracrRNA, Cas9 once again behaved more like a scissor.

Other experiments showed that in lab-grown bacteria with a plentiful amount of long form tracrRNA, levels of all CRISPR-related genes were very low. When the long form tracrRNA was removed from bacteria, however, expression of CRISPR-Cas9 genes increased a hundredfold.

Bacterial cells lacking the long form tracrRNA were cultured in the laboratory for three days and compared with similarly cultured cells containing the long form tracrRNA. By the end of the experiment, bacteria without the long form tracrRNA had completely died off, suggesting that long form tracrRNA normally protects cells from the sickness and death that happen when CRISPR-Cas9 activity is very high.

“We started to get the idea that the long form was repressing but not eliminating its own CRISPR-related activity,” says Workman.

To see if the long form tracrRNA could be re-programmed to repress other bacterial genes, the research team altered the long form tracrRNA’s spacer region to let it sit on a gene that produces green fluorescence. Bacteria with this mutated version of long form tracrRNA glowed less green than bacteria containing the normal long form tracrRNA, suggesting that the long form tracrRNA can be genetically engineered to dial down other bacterial genes.

Another research team, from Emory University, found that in the parasitic bacteria Francisella novicida, Cas9 behaves as a dimmer switch for a gene outside the CRISPR-Cas9 region. The CRISPR-Cas9 system in the Johns Hopkins study is more widely used by scientists as a gene-cutting tool, and the Johns Hopkins team’s findings provide evidence that the dimmer action controls the CRISPR-Cas9 system in addition to other genes.

The researchers also found the genetic components of long form tracrRNA in about 40% of the Streptococcus group of bacteria. Further study of bacterial strains that don’t have the long form tracrRNA, says Workman, will potentially reveal whether their CRISPR-Cas9 systems are intact, and other ways that bacteria may dial back the CRISPR-Cas9 system.

The dimmer capability that the experiments uncovered, says Modell, offers opportunities to design new or better CRISPR-Cas9 tools aimed at regulating gene activity for research purposes. “In a gene editing scenario, a researcher may want to cut a specific gene, in addition to using the long form tracrRNA to inhibit gene activity,” he says.

Here’s a link to and a citation for the paper,

A natural single-guide RNA repurposes Cas9 to autoregulate CRISPR-Cas expression by Rachael E. Workman, Teja Pammi, Binh T.K. Nguyen, Leonardo W. Graeff, Erika Smith, Suzanne M. Sebald, Marie J. Stoltzfus, Chad W. Euler, Joshua W. Modell. Cell DOI:https://doi.org/10.1016/j.cell.2020.12.017 Published Online:J anuary 08, 2021

This paper is behind a paywall.

One-dimensional quantum nanowires and Majorana zero modes

Length but no width or height? That’s a quantum nanowire according to a Jan. 18, 2021 news item on Nanowerk (Note: A link has been removed),

Why is studying spin properties of one-dimensional quantum nanowires important?

Quantum nanowires–which have length but no width or height–provide a unique environment for the formation and detection of a quasiparticle known as a Majorana zero mode.

A new UNSW [University of New South Wales]-led study (Nature Communications, “New signatures of the spin gap in quantum point contacts”) overcomes previous difficulty detecting the Majorana zero mode, and produces a significant improvement in device reproducibility.

Potential applications for Majorana zero modes include fault-resistant topological quantum computers, and topological superconductivity.

A Jan. 19 (?), 2021 ARC (Australian Research Council) Centre of Excellence in Future Low-Energy Electronics Technologies (or FLEET) press release (also on EurekAlert), which originated the news item, provides more detail about the research,

MAJORANA FERMIONS IN 1D WIRES

A Majorana fermion is a composite particle that is its own antiparticle.

Antimatter explainer: Every fundamental particle has a corresponding antimatter particle, with the same mass but opposite electrical charge. For example, the antiparticle of an electron (charge -1) is a positron (charge +1)

Such unusual particle’s interest academically and commercially comes from their potential use in a topological quantum computer, predicted to be immune to the decoherence that randomises the precious quantum information.

Majorana zero modes can be created in quantum wires made from special materials in which there is a strong coupling between their electrical and magnetic properties.

In particular, Majorana zero modes can be created in one-dimensional semiconductors (such as semiconductor nanowires) when coupled with a superconductor.

In a one-dimensional nanowire, whose dimensions perpendicular to length are small enough not to allow any movement of subatomic particles, quantum effects predominate.

NEW METHOD FOR DETECTING NECESSARY SPIN-ORBIT GAP

Majorana fermions, which are their own antiparticle, have been theorised since 1937, but have only been experimentally observed in the last decade. The Majorana fermion’s ‘immunity’ to decoherence provides potential use for fault-tolerant quantum computing.

One-dimensional semiconductor systems with strong spin-orbit interaction are attracting great attention due to potential applications in topological quantum computing.

The magnetic ‘spin’ of an electron is like a little bar magnet, whose orientation can be set with an applied magnetic field.

In materials with a ‘spin-orbit interaction’ the spin of an electron is determined by the direction of motion, even at zero magnetic field. This allows for all electrical manipulation of magnetic quantum properties.

Applying a magnetic field to such a system can open an energy gap such that forward -moving electrons all have the same spin polarisation, and backward-moving electrons have the opposite polarisation. This ‘spin-gap’ is a pre-requisite for the formation of Majorana zero modes.

Despite intense experimental work, it has proven extremely difficult to unambiguously detect this spin-gap in semiconductor nanowires, since the spin-gap’s characteristic signature (a dip in its conductance plateau when a magnetic field is applied) is very hard to distinguish from unavoidable the background disorder in nanowires.

The new study finds a new, unambiguous signature for the spin-orbit gap that is impervious to the disorder effects plaguing previous studies.

“This signature will become the de-facto standard for detecting spin-gaps in the future,” says lead author Dr Karina Hudson.

REPRODUCIBILITY

The use of Majorana zero modes in a scalable quantum computer faces an additional challenge due to the random disorder and imperfections in the self-assembled nanowires that host the MZM.

It has previously been almost impossible to fabricate reproducible devices, with only about 10% of devices functioning within desired parameters.

The latest UNSW results show a significant improvement, with reproducible results across six devices based on three different starting wafers.

“This work opens a new route to making completely reproducible devices,” says corresponding author Prof Alex Hamilton UNSW).

Here’s a link to and a citation for the paper,

New signatures of the spin gap in quantum point contacts by K. L. Hudson, A. Srinivasan, O. Goulko, J. Adam, Q. Wang, L. A. Yeoh, O. Klochan, I. Farrer, D. A. Ritchie, A. Ludwig, A. D. Wieck, J. von Delft & A. R. Hamilton. Nature Communications volume 12, Article number: 5 (2021) DOI: https://doi.org/10.1038/s41467-020-19895-3 Published: 04 January 2021

This paper is open access.

For anyone who might find references to UNSW and ARC/FLEET confusing, I found this in the ARC Centre of Excellence in Future Low-Energy Electronics Technologies Wikipedia entry,

The ARC Centre of Excellence in Future Low-Energy Electronics Technologies (or FLEET) is a collaboration …

FLEET is an Australian initiative, headquartered at Monash University, and in conjunction with the Australian National University, the University of New South Wales, the University of Queensland, RMIT University, the University of Wollongong and Swinburne University of Technology, complemented by a group of Australian and international partners. It is funded by the Australian Research Council [ARC] and by the member universities. [emphases as seen here are mine]

‘Greener’ lithium mining in Canada

A February 19, 2021 article by Pamela Fieber for CBC (Canadian Broadcasting Corporation) news online features news of a Calgary (Alberta) company, Summit Nanotech, and a greener way to mine lithium (Note: A link has been removed),

Amanda Hall was on top of a mountain in Tibet when inspiration struck. 

“I saw a Tibetan monk reach into his robe and pull out an iPhone,” Hall told the Calgary Eyeopener [CBC radio programme].

“If there’s an iPhone at the top of a mountain in Tibet, where isn’t there an iPhone on this planet? And then it just got me thinking about batteries and battery technology and energy and how we store that energy.”

On her return to Calgary, the accomplished geophysicist began looking into a better, greener way to mine lithium — the essential ingredient in lithium-ion batteries, which power electric cars and smartphones.

This led to her founding the company, Summit Nanotech in 2018 and developing nanotechnology, which works with materials at the molecular or atomic level to selectively filter lithium out of the wasted saltwater brine used in oil wells.

It’s completely different from the way lithium is traditionally mined.

Sarah Offin’s November 12, 2020 article for Global TV News offers insight into the technology developed by Hall’s company (Note: Links have been removed),

Since the downturn in the oil and gas industry, there have been repeated calls for Alberta to diversify its economy. The province invests hundreds of millions of dollars every year to help grow both the tech and green energy sectors, industries that could have a bright future in a province rich with talent.

Amanda Hall is a prime example of that. She was able to draw on her experience in resource extraction with Alberta’s oil and gas industry, developing green technology to be used in energy storage.

Hall developed the only female-led mining technology company in the world: Summit Nanotech Corp. Using nanotechnology, Hall and her team say they have created an improved method of lithium-ion resource extraction from produced brine water.

“We’ve come up with a much more elegant approach — I say, feminine, approach — at bringing a resource out of the ground, and then giving it to the electric vehicle sector,” Hall said.

Using sponges developed through nanoscience, Hall and her team have created technology that will allow producers to extract lithium directly from the wellhead without the need for expansive ponds and toxic chemicals. The process is expected to reduce costs and decrease chemical waste by 90 per cent.

The firm’s website touts that its process is the most “green lithium extraction in the world.”

“The sponge has lithium selective cavities in it, just the exact size of a lithium-ion. And so, as if you put a fluid in against this sponge, it will only suck up lithium, nothing else, and it holds on to it. And then when you wash it, you wash the lithium off the sponge just by changing the environment it’s in. So we don’t have to use any acids,” Hall said.

Hall and her team have spent the last two-and-a-half years in the lab perfecting their design and are now building the company’s first full-scale 12-metre tall unit. “It’s our baby, but it’s huge,” Hall said. “It’s a mini-refinery, essentially.”

That “mini-refinery” will then be sent via shipping container to the first of the company’s three pilot partners: Lithium Chile.

The other two partners are Saskatchewan-based Prairie Lithium and 3 Proton Lithium (3PL) Operating Inc. in Nevada.

For anyone interested in the business and investment aspects (there’s mention of Elon Musk in both stories) check out Fieber’s February 19, 2021 article and Offin’s November 12, 2020 article.

You can find Summit Nanotech here. I found a little more information about the company’s technology on the Lithium webpage,

denaLi 1.0
Direct Lithium Extraction
(DLE) Process

Summit Nanotech has designed an innovative new method to generate battery grade lithium compounds from brine fluids, named denaLi. This process is the most green lithium extraction technology in the world. Lithium carbonate and lithium hydroxide can be sold at market value to supply the growing demand from electric vehicle battery manufacturers. 

Interconnected modules using nanoporous membranes in a unique arrangement are synthesized with specific filtration functions. Carbon dioxide is used to initiate end product precipitation. Discrete power generation modules are selected to work together to harvest and store available geothermal, solar, wind, and hydroelectric power from the system’s environment.

Prairie Lithium, the Saskatchewan-based company mentioned in Offin’s article, co-founded a joint venture specifically dedicated to lithium extraction from brine (to begin with) in 2020 according to Jonathan Guignard in a June 3, 2020 article for Global TV news (Note: Links have been removed),

Saskatchewan will soon be home to a new lithium production project.

The Prairie-LiEP Critical Mineral (PLCM) joint venture is being undertaken by Prairie Lithium Corp. and LiEP Energy Ltd [headquarted in Calgary, Alberta].

Their two-stage pilot project will produce lithium hydroxide from some of the province’s oilfield brines.

The first stage of the project is based in Regina and is set to being in July. The second stage is set for the second half of 2021, with field operations in southern parts of the province.

“PLCM Joint Venture is excited to begin Stage 1 of the pilot operation in Saskatchewan this summer,” said Prairie president and CEO Zach Maurer and LiEP president and CEO Haafiz Hasham.

I can’t find any mention of the PLCM joint venture on the Prairie Lithium website but there is what appears to be a June 3, 2020 news release announcing the venture on the LiEP Energy website but there is no further information on that website.

On another front, Lithium Chile, which seems to be headquartered in Calgary with extensive lithium mining projects in Chile, has a brief mention of their partnership with Summit Nanotech in a December 24, 2020 posting (on the News webpage) by Steve (Cochrane; president and chief executive officer),

Lastly our partnership with Summit continues to move forward and we are very happy to be working with them. I have attached our recently negotiated LOI [letter of intent] for our JV [joint venture] pilot project in Chile. We should have the definitive agreement signed early in the new year. They plan to have their pilot unit completed and shipped by July of 2021 so a planned test is scheduled for late summer next year. This gives us the time to get back on one or more of our lithium prospects to prepare for our pilot project. They continue to see great results in the lab and hope this is the breakthrough we all want to see for an efficient cost and environmentally effective method of producing lithium from brines.

I cannot find any further mention on the Lithium Chile website about their joint venture with Summit Nanotech.

The big question is whether or not this technology can be scaled for industrial use. I wish them good luck with the effort.

All this talk about lithium extraction and other natural resource extraction brought to mind Harold Innis and his staples theory of Canadian history, culture, and economy. From the Harold Innis Wikipedia entry (Note: Links have been removed),

Harold Adams Innis FRSC (1894 – 1952) was a Canadian professor of political economy at the University of Toronto and the author of seminal works on media, communication theory, and Canadian economic history. He helped develop the staples thesis, [emphasis mine] which holds that Canada’s culture, political history, and economy have been decisively influenced by the exploitation and export of a series of “staples” such as fur, fishing, lumber, wheat, mined metals [emphasis mine], and coal. The staple thesis dominated economic history in Canada from the 1930s to 1960s, and continues to be a fundamental part of the Canadian political economic tradition.[8]

There you have it.

Fungal wearable tech and building materials

This is the first time I’ve seen wearable tech based on biological material, in this case, fungi. In diving further into this material (wordplay intended), I discovered some previous work on using fungi for building materials, which you’ll find later in this posting.

Wearable tech and more

A January 18, 2021 news item on phys.org provides some illumination on the matter,

Fungi are among the world’s oldest and most tenacious organisms. They are now showing great promise to become one of the most useful materials for producing textiles, gadgets and other construction materials. The joint research venture undertaken by the University of the West of England, Bristol, the U.K. (UWE Bristol) and collaborators from Mogu S.r.l., Italy, Istituto Italiano di Tecnologia, Torino, Italy and the Faculty of Computer Science, Multimedia and Telecommunications of the Universitat Oberta de Catalunya (UOC) has demonstrated that fungi possess incredible properties that allow them to sense and process a range of external stimuli, such as light, stretching, temperature, the presence of chemical substances and even electrical signals. [emphasis mine]

This could help pave the way for the emergence of new fungal materials with a host of interesting traits, including sustainability, durability, repairability and adaptability. Through exploring the potential of fungi as components in wearable devices, the study has verified the possibility of using these biomaterials as efficient sensors with endless possible applications.

A January 18, 2021 Universitat Oberta de Catalunya (UOC) press release (also on EurekAlert), which originated the news item, describes this vision for future wearable tech based on fungi,

Fungi to make smart wearables even smarter

People are unlikely to think of fungi as a suitable material for producing gadgets, especially smart devices such as pedometers or mobile phones. Wearable devices require sophisticated circuits that connect to sensors and have at least some computing power, which is accomplished through complex procedures and special materials. This, roughly speaking, is what makes them “smart”. The collaboration of Prof. Andrew Adamatzky and Dr. Anna Nikolaidou from UWE Bristol’s Unconventional Computing Laboratory, Antoni Gandia, Chief Technology Officer at Mogu S.r.l., Prof. Alessandro Chiolerio from Istituto Italiano di Tecnologia, Torino, Italy and Dr. Mohammad Mahdi Dehshibi, researcher with the UOC’s Scene Understanding and Artificial Intelligence Lab (SUNAI) have demonstrated that fungi can be added to the list of these materials.

Indeed, the recent study, entitled “Reactive fungal wearable” and featured in Biosystems, analyses the ability of oyster fungus Pleurotus ostreatus to sense environmental stimuli that could come, for example, from the human body. In order to test the fungus’s response capabilities as a biomaterial, the study analyses and describes its role as a biosensor with the ability to discern between chemical, mechanical and electrical stimuli.

“Fungi make up the largest, most widely distributed and oldest group of living organisms on the planet,” said Dehshibi, who added, “They grow extremely fast and bind to the substrate you combine them with”. According to the UOC researcher, fungi are even able to process information in a way that resembles computers.

“We can reprogramme a geometry and graph-theoretical structure of the mycelium networks and then use the fungi’s electrical activity to realize computing circuits,” said Dehshibi, adding that, “Fungi do not only respond to stimuli and trigger signals accordingly, but also allow us to manipulate them to carry out computational tasks, in other words, to process information”. As a result, the possibility of creating real computer components with fungal material is no longer pure science fiction. In fact, these components would be capable of capturing and reacting to external signals in a way that has never been seen before.

Why use fungi?

These fungi have less to do with diseases and other issues caused by their kin when grown indoors. What’s more, according to Dehshibi, mycelium-based products are already used commercially in construction. He said: “You can mould them into different shapes like you would with cement, but to develop a geometric space you only need between five days and two weeks. They also have a small ecological footprint. In fact, given that they feed on waste to grow, they can be considered environmentally friendly”.

The world is no stranger to so-called “fungal architectures” [emphasis mine], built using biomaterials made from fungi. Existing strategies in this field involve growing the organism into the desired shape using small modules such as bricks, blocks or sheets. These are then dried to kill off the organism, leaving behind a sustainable and odourless compound.

But this can be taken one step further, said the expert, if the mycelia are kept alive and integrated into nanoparticles and polymers to develop electronic components. He said: “This computer substrate is grown in a textile mould to give it shape and provide additional structure. Over the last decade, Professor Adamatzky has produced several prototypes of sensing and computing devices using the slime mould Physarum polycephalum, including various computational geometry processors and hybrid electronic devices.”

The upcoming stretch

Although Professor Adamatzky found that this slime mould is a convenient substrate for unconventional computing, the fact that it is continuously changing prevents the manufacture of long-living devices, and slime mould computing devices are thus confined to experimental laboratory set-ups.

However, according to Dehshibi, thanks to their development and behaviour, basidiomycetes are more readily available, less susceptible to infections, larger in size and more convenient to manipulate than slime mould. In addition, Pleurotus ostreatus, as verified in their most recent paper, can be easily experimented on outdoors, thus opening up the possibility for new applications. This makes fungi an ideal target for the creation of future living computer devices.

The UOC researcher said: “In my opinion, we still have to address two major challenges. The first consists in really implementing [fungal system] computation with a purpose; in other words, computation that makes sense. The second would be to characterize the properties of the fungal substrates via Boolean mapping, in order to uncover the true computing potential of the mycelium networks.” To word it another way, although we know that there is potential for this type of application, we still have to figure out how far this potential goes and how we can tap into it for practical purposes.

We may not have to wait too long for the answers, though. The initial prototype developed by the team, which forms part of the study, will streamline the future design and construction of buildings with unique capabilities, thanks to their fungal biomaterials. The researcher said: “This innovative approach promotes the use of a living organism as a building material that is also fashioned to compute.” When the project wraps up in December 2022, the FUNGAR project will construct a large-scale fungal building in Denmark and Italy, as well as a smaller version on UWE Bristol’s Frenchay Campus.

Dehshibi said: “To date, only small modules such as bricks and sheets have been manufactured. However, NASA [US National Aeronautics Space Administration] is also interested in the idea and is looking for ways to build bases on the Moon and Mars to send inactive spores to other planets.” To conclude, he said: “Living inside a fungus may strike you as odd, but why is it so strange to think that we could live inside something living? It would mark a very interesting ecological shift that would allow us to do away with concrete, glass and wood. Just imagine schools, offices and hospitals that continuously grow, regenerate and die; it’s the pinnacle of sustainable life.”

For the Authors of the paper, the point of fungal computers is not to replace silicon chips. Fungal reactions are too slow for that. Rather, they think humans could use mycelium growing in an ecosystem as a “large-scale environmental sensor.” Fungal networks, they reason, are monitoring a large number of data streams as part of their everyday existence. If we could plug into mycelial networks and interpret the signals, they use to process information, we could learn more about what was happening in an ecosystem.

Here’s a link to and a citation for the paper,

Reactive fungal wearable by Andrew Adamatzky, Anna Nikolaidou, Antoni Gandia, Alessandro Chiolerio, Mohammad Mahdi Dehshibi. Biosystems Volume 199, January 2021, 104304 DOI: https://doi.org/10.1016/j.biosystems.2020.104304

This paper is behind a paywall.

Fungal architecture and building materials

Here’s a video, which shows the work which inspired the fungal architecture that Dr. Dehshibi mentioned in the press release about wearable tech,

The video shows a 2014 Hy-Fi installation by The Living for MoMA (Museum of Modern Art) PS1 in New York City. Here’s more about HyFi and what it inspired from a January 15, 2021 article by Caleb Davies for the EU (European Union) Research and Innovation Magazine and republished on phys.org (Note: Links have been removed),

In the summer of 2014 a strange building began to take shape just outside MoMA PS1, a contemporary art centre in New York City. It looked like someone had started building an igloo and then got carried away, so that the ice-white bricks rose into huge towers. It was a captivating sight, but the truly impressive thing about this building was not so much its looks but the fact that it had been grown.

The installation, called Hy-Fi, was designed and created by The Living, an architectural design studio in New York. Each of the 10,000 bricks had been made by packing agricultural waste and mycelium, the fungus that makes mushrooms, into a mould and letting them grow into a solid mass.

This mushroom monument gave architectural researcher Phil Ayres an idea. “It was impressive,” said Ayres, who is based at the Centre for Information Technology and Architecture in Copenhagen, Denmark. But this project and others like it were using fungus as a component in buildings such as bricks without necessarily thinking about what new types of building we could make from fungi.

That’s why he and three colleagues have begun the FUNGAR project—to explore what kinds of new buildings we might construct out of mushrooms.

FUNGAR (Fungal Architectures) can be found here, Mogu can be found here, and The Living can be found here.

Put a ring on it: preventing clumps of gold nanoparticles

Caption: A comparison of how linear PEG (left) and cyclic PEG (right) attach to a gold nanoparticle Credit: Yubo Wang, Takuya Yamamoto

A January 20, 2021 news item on phys.org focuses on work designed to stop gold nanoparticles from clumping together (Note: A link has been removed),

Hokkaido University scientists have found a way to prevent gold nanoparticles from clumping, which could help towards their use as an anti-cancer therapy.

Attaching ring-shaped synthetic compounds to gold nanoparticles helps them retain their essential light-absorbing properties, Hokkaido University researchers report in the journal Nature Communications.

A January 20, 2021 Hokkaido University press release (also on EurekAlert but published Jan. 21, 2020), which originated the news item, elaborates on the work,

Metal nanoparticles have unique light-absorbing properties, making them interesting for a wide range of optical, electronic and biomedical applications. For example, if delivered to a tumour, they could react with applied light to kill cancerous tissue. A problem with this approach, though, is that they easily clump together in solution, losing their ability to absorb light. This clumping happens in response to a variety of factors, including temperature, salt concentration and acidity.

Scientists have been trying to find ways to ensure nanoparticles stay dispersed in their target environments. Covering them with polyethylene glycol, otherwise known as PEG, has been relatively successful at this in the case of gold nanoparticles. PEG is biocompatible and can prevent gold surfaces from clumping together in the laboratory and in living organisms, but improvements are still needed.

Applied chemist Takuya Yamamoto and colleagues at Hokkaido University, The University of Tokyo, and Tokyo Institute of Technology found that mixing gold nanoparticles with ring-shaped PEG, rather than the normally linear PEG, significantly improved dispersion. The ‘cyclic-PEG’ (c-PEG) attaches to the surfaces of the nanoparticles without forming chemical bonds with them, a process called physisorption. The coated nanoparticles remained dispersed when frozen, freeze-dried and heated.

The team tested the c-PEG-covered gold nanoparticles in mice and found that they cleared slowly from the blood and accumulated better in tumours compared to gold nanoparticles coated with linear PEG. However, accumulation was lower than desired levels, so the researchers recommend further investigations to fine-tune the nanoparticles for this purpose.

Associate Professor Takuya Yamamoto is part of the Laboratory of Chemistry of Molecular Assemblies at Hokkaido University, where he studies the properties and applications of various cyclic chemical compounds.

Here’s a link to and a citation for the paper,

Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol) by Yubo Wang, Jose Enrico Q. Quinsaat, Tomoko Ono, Masatoshi Maeki, Manabu Tokeshi, Takuya Isono, Kenji Tajima, Toshifumi Satoh, Shin-ichiro Sato, Yutaka Miura & Takuya Yamamoto. Nature Communications volume 11, Article number: 6089 (2020) DOI: https://doi.org/10.1038/s41467-020-19947-8 Published: 30 November 2020

This paper is open access.