Monthly Archives: August 2021

Illustration. Credit: Yuval Robichek, Weizmann Institute of Science

Proteins communicating through the DNA molecule constitute a newly discovered genetic switch.

Proteins can communicate through DNA, conducting a long-distance dialogue that serves as a kind of genetic switch, according to Weizmann Institute of Science researchers. They found that the binding of proteins to one site of a DNA molecule can physically affect another binding site at a distant location, and that this peer effect activates certain genes. This effect had previously been observed in artificial systems, but the Weizmann study is the first to show it takes place in the DNA of living organisms.

A team headed by Dr. Hagen Hofmann of the Chemical and Structural Biology Department made this discovery while studying a peculiar phenomenon in the soil bacteria Bacillus subtilis. A small minority of these bacteria demonstrate a unique skill: an ability to enrich their genomes by taking up bacterial gene segments scattered in the soil around them. This ability depends on a protein called ComK, a transcription factor, which binds to the DNA to activate the genes that make the scavenging possible. However, it was unknown how exactly this activation works.

(l-r) Dr. Nadav Elad, Dr. Haim Rozenberg, Dr. Gabriel Rosenblum, Jakub Jungwirth and Dr. Hagen Hofmann. Twisting a rope from one end. Credit: Weizmann Institute of Science

Staff Scientist Dr. Gabriel Rosenblum led this study, in which the researchers explored the bacterial DNA using advanced biophysical tools single-molecule FRET and cryogenic electron microscopy. In particular, they focused on the two sites on the DNA molecule to which ComK proteins bind.

They found that when two ComK molecules bind to one of the sites, it sets off a signal that facilitates the binding of two additional ComK molecules at the second site. The signal can travel between the sites because physical changes triggered by the original proteins binding create tension that is transmitted along the DNA, something like twisting a rope from one end. Once all four molecules are bound to the DNA, a threshold is passed, switching on the bacteriums gene scavenging ability.

We were surprised to discover that DNA, in addition to containing the genetic code, acts like a communication cable, transmitting information over a relatively long distance from one protein binding site to another, Rosenblum says.

A 3D reconstruction from single particles of bacterial DNA (gray) and ComK proteins (red), imaged by cryogenic electron microscopy, viewed from the front (left) and at a 90 degrees rotation. ComK molecules bound to two sites communicate through the DNA segment between them. Credit: Weizmann Institute of Science

By manipulating the bacterial DNA and monitoring the effects of these manipulations, the scientists clarified the details of the long-distance communication within the DNA. They found that for communication or cooperation between two sites to occur, these sites must be located at a particular distance from one another, and they must face the same direction on the DNA helix. Any deviation from these two conditions for example, increasing the distance weakened the communication. The sequence of genetic letters running between the two sites was found to have little effect on this communication, whereas a break in the DNA interrupted it completely, providing further evidence that this communication occurs through a physical connection.

Knowing these details may help design molecular switches of desired strengths for a variety of applications. The latter may include genetically engineering bacteria to clean up environmental pollution or synthesizing enzymes to be used as drugs.

Long-distance communication within a DNA molecule is a new type of regulatory mechanism one that opens up previously unavailable methods for designing the genetic circuits of the future, Hofmann says.

Reference: Allostery through DNA drives phenotype switching by Gabriel Rosenblum, Nadav Elad, Haim Rozenberg, Felix Wiggers, Jakub Jungwirth and Hagen Hofmann, 20 May 2021, Nature Communications.DOI: 10.1038/s41467-021-23148-2

The research team included Dr. Nadav Elad of Weizmanns Chemical Research Support Department; Dr. Haim Rozenberg and Dr. Felix Wiggers of the Chemical and Structural Biology Department; and Jakub Jungwirth of the Chemical and Biological Physics Department.

Dr. Hagen Hofmann is the incumbent of the Corinne S. Koshland Career Development Chair in Perpetuity.

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Calling Through the DNA Wire: A Newly Discovered Genetic Switch - SciTechDaily

A GPS system that suggests the fastest route to a destination. A voice-activated virtual assistant, such as Siri by Apple. Personalized recommendations for Netflix by Netflix. And the ability of Facebook to recognize your face and tag you in a friends photo.

These types of technology now are so frequent in our daily lives that many dont think twice about them. But heres the true reality: These unprecedented advances in autonomous technology, sustainability, robotics and analytics are disrupting traditional business models.

These advances are part of what is now being called the Fourth Industrial Revolution, or 4IR, a period in which the lines between the physical, digital and biological spheres are being blurred. It is a fusion of advances in artificial intelligence, robotics, the Internet of Things, 3D printing, genetic engineering, quantum computing and other technologies.

All of this and more will be discussed in an upcoming panel discussion sponsored by Middlesex County.

Leading Locally in the Fourth Industrial Revolution: The Future of Automation will be presented from 8-11 a.m. Sept. 9 at Middlesex College in Edison.

Register for the event here.

The panel includes:

The panel, the second in the countys three-part business series, will discuss how 4IR is behind the many products and services that are fast becoming indispensable to modern life.

Most specifically, the panel will discuss:

The 4IR figures to have important and lasting effects on the future of business. Embracing 4IR likely will help companies deliver results and hold greater resilience, especially during uncertain times.

Opportunities include:

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The Fourth Industrial Revolution is here: Panel will show how it can (and will) help your business - ROI-NJ.com

On a cold December day in Norwich, England, Cathie Martin met me at a laboratory inside the John Innes Centre, where she works.

A plant biologist, Professor Martin has spent almost two decades studying tomatoes, and I had travelled to see her because of a particular one she created a lustrous, dark purple variety that is unusually high in antioxidants, with twice the amount found in blueberries.

At 66, Martin has silver-white hair, a strong chin, and sharp eyes that give her a slightly elfin look. She has long been interested in how plants produce beneficial nutrients.

The purple tomato is the first she designed to have more anthocyanin, a naturally occurring anti-inflammatory compound.

All higher plants have a mechanism for making anthocyanins, Martin explained when we met. A tomato plant makes them as well, in the leaves. We just put in a switch that turns on anthocyanin production in the fruit.

Martin noted that, while there are other tomato varieties that look purple, they have anthocyanins only in the skin, so the health benefits are slight.

People say, oh, there are purple tomatoes already, but they dont have these kind of levels, she said.

The difference is significant. When cancer-prone mice were given Martins purple tomatoes as part of their diet, they lived 30% longer than mice fed the same quantity of ordinary tomatoes. They were also less susceptible to inflammatory bowel disease.

After the publication of Martins first paper showing the anti-cancer benefit of her tomatoes, in the academic journal Nature Biotechnology in 2008, newspapers and television stations began calling.

The coverage, she recalled. Days and days and days and days of it.

She considered making the tomato available in shops or offering it online as a juice. However, because the plant contained a pair of genes from a snapdragon thats what spurs the tomatoes to produce more anthocyanin it would be classified as a genetically modified organism (GMO).

That designation brings with it a host of obligations, not just in Britain but many other countries.

In 2018, the Irish Government announced the prohibition/restriction of the commercial cultivation of genetically modified crops.

Then minister for climate action and environment Denis Naughten said that it was a very significant development and that it was critically important that Ireland takes whatever steps are necessary to maintain our GMO cultivation-free status, which is a key element of our international reputation as a green, sustainable food producer.

In the US, Prof Martin had envisioned making the juice on a small scale, but just to go through the Food and Drug Administration (FDA) approval process would cost $1m (850,000). Adding US Department of Agriculture (USDA) approval could push that amount even higher. (Tomato juice is known as a GM product and is regulated by the FDA. However, because a tomato has seeds that can germinate, it is also regulated by the USDA.)

I thought, 'this is ridiculous', Martin told me.

She eventually did put together the required documentation, but the process, and subsequent revisions, took almost six years.

Our 'business model is that we have this tiny company which has no employees, Martin said with a laugh.

Of course, the FDA is used to the bigger organisations [global agricultural conglomerates such as DowDuPont or Syngenta] so this is where you get a bit of a problem.

When they say, oh, we want a bit more data on this, its easy for a corporation. For me its me that has to do it. And I cant just throw money at it.

Martin admitted that, as an academic, she hadnt been as focused on getting the tomato to market as she might have been. (Her colleague Jonathan Jones, a plant biologist, eventually stepped in to assist.)

However, the process has also been slow because the purple tomato, if approved, would be one of only a very few GMO fruits or vegetables sold directly to consumers. The others include Rainbow papayas, which were modified to resist ringspot virus; a variety of sweetcorn; some russet potatoes; and Arctic apples, which were developed in Canada and resist browning.

It also might be the first genetically modified anything that people actually want.

Since their introduction in the mid-1990s, GMOs have remained wildly unpopular with consumers, who see them as dubious tools of Big Ag, with potentially sinister impacts on both people and the environment.

The purple tomato could perhaps change that. Unlike commercial GMO crops such as soy and canola Martins tomato wasnt designed for profit and would be grown in small batches rather than on millions of acres: essentially the opposite of industrial agriculture.

The additional genes it contains (from the snapdragon, itself a relative of the tomato plant) act only to boost production of anthocyanin, a nutrient that tomatoes already make.

More importantly, the fruits anti-inflammatory and anti-cancer properties, which seem considerable, are things that many of us actively want. Nonetheless, the future of the purple tomato is far from certain.

Theres just so much baggage around anything genetically modified, Martin said. Im not trying to make money. Im worried about peoples health. But in peoples minds its all Dr Frankenstein and trying to rule the world.

In the three decades since GMO crops were introduced, only a tiny number have been developed and approved for sale, almost all of them products made by large agrochemical companies such as Monsanto.

However, within those categories, GMOs have taken over much of the market. Roughly 94% of soybeans grown in the US are genetically modified, as is more than 90% of all corn, rapeseed (canola), and sugarbeet, together covering roughly 170m acres of cropland.

At the same time, resistance to GMO foods has only become more entrenched. The market for products certified to be non-GMO has increased more than 70-fold since 2010, from roughly 350m that year to 26bn by 2018.

There are now more than 55,000 products carrying the Non-GMO Project Verified label on their packaging.

For many of us, the rejection of GMOs is instinctive. Our distrust might also stem from the way GMOs were introduced.

When the agribusiness giant Monsanto released its first GMO crop in 1996 a herbicide-resistant soybean the company was in need of cash.

By adding a gene from a bacterium, it hoped to create crops that were resistant to glyphosate, the active ingredient in its trademark herbicide, RoundUp, enabling farmers to spray weeds liberally without also killing the soy plant something that wasnt possible with traditional herbicides. Commercially, the idea succeeded.

By 2003, RoundUp Ready corn and soy seeds dominated the market, and Monsanto had become the largest producer of genetically engineered seeds, responsible for more than 90% of GMO crops planted globally.

However, the companys rollout also alarmed and antagonised farmers, who were required to sign restrictive contracts to use the patented seeds and whom Monsanto aggressively prosecuted.

At one point, the company had a 75-person team dedicated solely to investigating farmers suspected of saving seed a traditional practice in which seeds from one years crop are saved for planting the following year and prosecuting them on charges of intellectual property infringement.

Environmental groups were also concerned because of the skyrocketing use of RoundUp and the abrupt decline in agricultural diversity.

A perfect storm

It was kind of a perfect storm, says Mark Lynas, an environmental writer and activist who protested against GMOs for over a decade.

You had this company that had made Agent Orange [the defoliant herbicide which is estimated to have sickened or disabled millions who came in contact with it when it was used by the US military during the Vietnam War] and PCBs [an environmental toxin that the US EPA banned in 1979] that was now using GMOs to intensify the worst forms of monoculture farming. I just remember feeling like we had to stop this thing.

Once public sentiment was set, it proved hard to shift, even when more beneficial products began to emerge.

One of these, Golden Rice, was made in 1999 by two university researchers hoping to combat vitamin A deficiency, a simple but devastating ailment that causes blindness in millions of people in Africa and Asia every year and can also be fatal.

However, the project foundered after protests by anti-GMO activists in Europe and the US, which in turn alarmed governments and populations in developing countries.

Lynas, who publicly disavowed his opposition to GMOs in 2013, says:

Probably the angriest Ive ever felt was when anti-GMO groups destroyed fields of Golden Rice growing in the Philippines. To see a crop that had such obvious life-saving potential ruined it would be like anti-vaxxer groups invading a laboratory and destroying a million vials of Covid vaccine.

In recent years, many environmental groups have also quietly walked back their opposition as evidence has mounted that existing GMOs are both safe to eat and not inherently bad for the environment.

The introduction of Bt corn, which contains a gene from Bacillus thuringiensis, a naturally insect-resistant bacterium that organic farmers routinely spray on crops, dropped the crops insecticide use by 35%.

A pest-resistant Bt eggplant has become popular in Bangladesh, where farmers have also embraced flood-tolerant scuba rice, engineered to survive being submerged for up to 14 days rather than just three.

Each year, Bangladesh and India lose roughly 4m tons of rice to flooding enough to feed 30m people and waste a corresponding volume of pesticides and herbicides, which then enter the groundwater.

However, in most of the rest of the world, such benefits can seem remote compared with what we think of as eating naturally. Thats especially true because, for many of us, GMOs and the harms of industrial agriculture (monocultures, overuse of pesticides and herbicides) remain inextricably linked.

Because of the way that GMOs were introduced to the public as a corporate product, focused on profit the whole technology got tarred, Lynas says. In peoples minds, its genetic engineering equals monoculture equals the broken food system. But it doesnt have to be that way.

Plant geneticists tend not to be overly concerned about the risks of GMOs, as long as the modifications are made with some care. As a 2016 report by the US National Academy of Sciences found, GMOs were generally safe, although it allowed that minor impacts were theoretically possible.

Fred Gould, a professor of agriculture who was chairman of the committee that prepared the 600-page report, noted that genetic changes that alter a metabolic pathway the cellular process that transforms biochemical elements into a particular nutrient or compound, like the anthocyanins in Martins tomato were especially important to study because they could cause cascading effects.

However, to me, Gould emphasised that many genetic modifications to food are trivial and extremely unlikely to have any measurable effect on people.

Weve been changing all these things already with conventional breeding, and so far were doing all right, Gould said. Making the same change with genetic engineering theres really no difference.

Almost everything we grow and eat today has had its DNA altered extensively. For millenniums, farmers, discovering that one version of a plant usually a random genetic mutant was hardier, or sweeter, or had smaller seeds, would cross it with another that, say, produced more fruit, in the hopes of getting both benefits.

However, the process was slow. Simply changing the colour of a tomato from red to yellow while preserving its other traits could take years of crossbreeding. And tomatoes are one of the easiest cases. Introducing even a minor change to a cherry through crossbreeding, I was told, could take up to 150 years.

To those who worry about GMOs, that slowness is reassuring. Yet the way nature alters things is also profoundly haphazard. Sometimes a plant will acquire one trait at the expense of another. Sometimes it actually becomes worse.

The same is true for agricultural crossbreeding. Not only is there no way to control which genes are kept and which are lost, the process also tends to introduce unwanted changes.

Commercial berry growers spent decades trying to create a domesticated version of the black raspberry through crossbreeding, but never succeeded: The thornless berries either tasted worse or produced almost no fruit, or they developed other problems.

Its also why meeting the needs of modern agriculture growing produce that can be shipped long distances and hold up in the shop and at home for more than a few days can result in tomatoes that taste like cardboard, or strawberries that arent as sweet as they used to be.

With conventional breeding, youre basically just shuffling the genetic deck, agricultural executive Tom Adams told me.

Youre never going to carry over only the gene you want.

In recent years, genetic engineering tools such as Crispr have offered a way around this imprecision, making it possible to identify which genes control which traits things such as colour, hardiness, sweetness and to change only those.

Its far more precise, says Andrew Allan, a plant biologist at the University of Auckland. Instead of rolling the dice, youre changing only the thing you want to change. And you can do it in one generation instead of 10 or 20.

From a regulatory perspective, Allan pointed out, all GMOs are treated the same, regardless of the modification and regardless of the scale. The policy is partly a holdover from the early days of genetic engineering, when less was known about the process and its effects. However, it has persisted, in part, because of powerful anti-GMO campaigning.

Eric Ward, co-chief executive of agricultural technology company AgBiome, described the situation as stuck in a closed loop.

He went on: People think, Well, if youve got this really strict regulatory system, then it must be really dangerous'. So it becomes self-reinforcing.

A few days before travelling to Norwich, I joined Martin at the Royal Society in London for the Future Food conference, a series of talks on genetic engineering in agriculture. There I met Haven Baker, a founder of a company called Pairwise, which was started to create fruits and vegetables that are genetically edited but not GMO.

I dont think we can change peoples minds about GMOs, Baker said. But gene editing is a clean slate. And maybe then GMOs will be able to follow.

Why crop scientists want to improve berries

In his talk, Baker noted that there were hundreds of kinds of berries in the world. However, among those we commonly call berries, we eat just four strawberries, raspberries, blueberries and blackberries.

Theres a reason the other varieties rarely reach us. Sometimes the fruit rots within days after picking (salmonberries), or the plant puts out fruit for only a few weeks in summer (cloudberries).

Sometimes the plant doesnt produce much fruit at all or is too thorny or sprawling for the fruit to be picked without a vast amount of labour.

Black raspberries, one fruit that Pairwise hopes to bring to market, used to be widely grown in North America until a virus decimated them. (The red raspberries we eat now originally came from Turkey.)

The revived version, which will be in field trials in 2024, has been engineered to be thornless and seedless, while retaining the fruits signature jammy flavour.

More recently, the company began a similar project with vegetables.

Very few of us eat the recommended daily allowance of fruit and vegetables, and teenagers eat even less. In an entire year, the average person consumes just a few heads of broccoli.

So how do we change that? Baker asked. People already know that theyre supposed to be eating vegetables. They just arent doing it. But if we can use gene editing to make broccoli slightly less bitter, maybe people and especially kids will eat more of it, and therefore be getting more fibre and more vitamins, which might make a difference in their long-term health.

A new, small-scale, beginning for GMO foods

There are some signs that the future of small-scale, bespoke GMO produce may already have begun.

In late April, Martin told me that the USDA had recently updated its regulations to allow more GMO plants to be grown outside, without a three-year field trial or in tightly contained greenhouses (the exceptions are plants or organisms with the potential to be a pest, pathogen or weed).

In the wake of this change, Martin and Jones are planning to make the purple tomato available first to home gardeners, who could grow it from seed as soon as next spring well before the commercially grown tomato reaches grocery stores. USDA approval is expected by December.

Theyre currently testing six varieties to find the most flavourful.

When we first developed the purple tomato, it was home gardeners who were most interested in it, Martin noted. With home gardening, its an opt-in system. Its up to you whether you want to grow it.

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GM foods: Our suspicion and fear may be a thing of the past - Irish Examiner

State College, Pennsylvania., August 30, 2021 / PRNewswire / -NeuExcell Therapeutics (www.neuexcell.com), A gene therapy company focused on neurodegenerative diseases has announced a Series Pre-A funding round of over $ 10 million. The round was led by Co-Win Ventures and was attended by other institutional investors Yuan Bio, Oriza Seed, Tsingyuan and Inno Angel.

We are honored to join this very reputable group of investors, he said. Peter Tombros, Chairman of the Board of Directors of NeuExcell Therapeutics. Investor experience and support will enable us to leverage our unique neuroregenerative gene therapy platform across multiple neurodegenerative indications. This funding strength validates our strategy and biotechnology. Further examine our science in the industry.

Professor Gong Chen, co-founder and chief scientific advisor of the company, said: There is an urgent need for breakthrough therapies like us.

I think this is a great opportunity to invest in experienced leadership, he said. Xin Huang, Managing Partner of Co-Win Ventures. NeuExcells unique technology has the potential to act as a platform for treating many neurodegenerative diseases, providing hope for breakthrough new therapies for patients who do not have the right choices today.

With the end of this successful pre-A round, we welcome him. Xin Huang Jonathan Sun attended the board meeting.

About NeuExcellTherapeutics

NeuExcell is a privately held early stage genetic engineering company headquartered in Pennsylvania, USA When Shanghai, China.. Its mission is to improve the lives of patients suffering from neurodegenerative diseases and damage to the central nervous system. Based on Professor Gong Chens scientific research, we have developed a potentially destructive nerve repair technique through the conversion of astrocytes to neurons. In vivo By introducing neural transcription factors through adeno-associated virus (AAV) -based gene therapy. NeuExcells pipeline covers major neurodegenerative diseases such as stroke, Huntingtons disease, amyotrophic lateral sclerosis (ALS), Alzheimers disease, Parkinsons disease, traumatic brain injury, spinal cord injury, and glioma. increase.

Founded in 2009, Co-Win Ventures is an early stage investor in healthcare and TMT with a focus on equality, transparency, sharing and innovation. Co-Wins business network China When USA..Total AUM is about US $ 1 billion, Co-Win aims to be a reliable partner for great entrepreneurs to build breakthrough technologies and businesses. Co-Win Ventures has helped more than 140 portfolio companies, including leading leaders in their respective sub-sectors, including Cytek, Connect, Thrive (acquired by Nasdaq-listed company EXAS), Taimei Technology, Genecast, Sinovation and Augta. ..

Source NeuExcellTherapeutics

NeuExcell Therapeutics Raises Over $ 10 Million Series Before Round To Continue Growth For The Company | State

Source link NeuExcell Therapeutics Raises Over $ 10 Million Series Before Round To Continue Growth For The Company | State

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NeuExcell Therapeutics Raises Over $ 10 Million Series Before Round To Continue Growth For The Company | State - Pennsylvanianewstoday.com

SARS-CoV-2, the virus responsible for COVID-19, has turned the world upside down. Experts have predicted that it will claim the lives of between 9-18 million worldwide. This is in addition to destroying the livelihoods, mental health and education of countless others. The pandemic will probably wreak havoc for many years to come, despite the remarkable speed of vaccine development. This is not helped by the emergence of new variants sweeping the world, which pose a serious threat to the success of vaccination and upcoming treatments.

It is difficult to predict the future pattern of SARS-CoV-2. Many scientists believe it will continue to circulate in pockets around the globe, meaning that it will become endemic in the same way as flu. In this context the number of infections remains relatively constant with occasional flare-ups that run the danger of turning into a pandemic. A lot depends on how widely the population around the world can be vaccinated and how long immunity lasts after natural infection or vaccination.

Long term, the best solution would be to develop a universal vaccine one that would help protect against all current variants of the coronavirus and any others that arise in the future. Without it, the world runs the risk of recurrent pandemics.

Given the difficulties encountered in creating a universal flu vaccine, this may seem a tall order. But a number of scientists believe it is possible based on the rapid development of the SARS-CoV-2 vaccines.

This story is part of Conversation InsightsThe Insights team generates long-form journalism and is working with academics from different backgrounds who have been engaged in projects to tackle societal and scientific challenges.

COVID-19 is in fact the third major infectious disease outbreak to have been triggered in the last two decades by a new coronavirus jumping from animals into humans, the other two being Sars and Mers.

To get a sense of how far a pan-coronavirus vaccine has progressed we spoke to a number of key players in the field. We are both experts in this area but come at it from very different angles Lara Marksis a historian of medicine with an interest in biotechnology and vaccines, while Ankur Mutreja has experience in tracking outbreaks and developing vaccines for infectious diseases. From our conversations, there appear to be a number of encouraging vaccine candidates on the horizon it is even possible that one could be developed for use in humans within 12 months.

One of the first people we spoke to was Richard Hatchett, the CEO of the Coalition for Epidemic Preparedness Innovations (Cepi). Set up in 2017, Cepi is a global partnership between public, private, philanthropic and civil society organisations that aims to compress the development of vaccines against emerging infectious diseases into 100 days a third of the time achieved with the first COVID-19 vaccines.

Envisaging equitable access to vaccines for all countries, in January 2021, Cepi announced it would raise and invest US$3.5 billion in vaccine research and development to strengthen global preparedness to pandemics, of which US$200 million has been put aside to develop a universal coronavirus vaccine. Such a vaccine would offer protection against a broad range of coronaviruses, regardless of their variants. This would reduce the need to modify the vaccine on a regular basis.

Hatchett described these vaccines as the holy grail. But he argued it may take years of investment. He said: If you want to grow a tree, the best thing to have done is to have planted it 20 years ago. And if you didnt do that, then the next best thing is to plant it today.

When asked about what the best vaccine would be going forward to deal with SARS-CoV-2, Hatchett replied:

We do not actually know specifically yet. This is really our first engagement with this virus, obviously, and weve watched it expand and unfold over time Were still gathering data and gaining experience on this. I think we need to have some humility about what we know currently and what we can know. We just have to be vigilant.

None of the scientists we interviewed were surprised to see SARS-CoV-2 mutating. All viruses mutate. They often undergo random genetic changes because the virus replication machinery is not perfect. It is a bit like a game of telephone where children repeat what they thought they heard, making mistakes all along the way so that the final message is very different from the original one. Whenever a virus develops one or more mutations it is considered a variant of the original virus.

The mutation process helps viruses to adapt and survive any onslaught from the hosts immune system, vaccination or drug treatment and natural competition. Viruses change faster when under such pressures.

Scientists have been monitoring the genetic variations in SARS-CoV-2 since the start of the pandemic. They do this by sequencing the total RNA (genome) of the virus collected from patient samples. The genome is the complete set of genetic instructions an organism needs to function and thrive.

Scientists in China managed to sequence the first SARS-CoV-2 genome just one week after the first patient was hospitalised with unusual pneumonia in Wuhan. First drafted on January 5 2020, the sequence revealed the virus to be a close relative of SARS-CoV-1, a human coronavirus which caused an outbreak of a severe respiratory disease SARS that first appeared in China in 2002 and then spread to many other countries. It also resembled a SARS-like coronavirus found in bats.

Comprising a single-strand of RNA, the SARS-CoV-2 genome turned out to be the longest genome of any known RNA virus. With the aid of sequencing scientists were quickly able to pinpoint the genes that carry the instructions for the spike protein, the part of the virus that helps it to invade human cells. This became an important target for the development of COVID-19 vaccine.

Initial genome sequencing data suggested that SARS-CoV-2 mutated much slower than most other RNA viruses, being half the rate of the virus responsible for flu and a quarter of that found for HIV. But its mutation rate has gathered speed over time, helped by the large reservoir of people it has infected and selection pressures.

Not all mutations are bad news. In some cases, they weaken the virus with the variant disappearing without a trace. But in other cases, they enable the virus to enter a hosts cells more easily or to escape the immune system more effectively, making it more difficult to prevent and treat.

So far, five new variants of concern have emerged with SARS-CoV-2. The first (alpha) was detected in south-east England in September 2020. Others were found shortly thereafter in South Africa (beta), Brazil (gamma), India (delta) and Peru (lambda). What is troubling about these new variants is that they are more transmissible, making them spread faster, which increases the likelihood of re-infection and a resurgence in cases. Every SARS-CoV-2 virus out there today is a variation of the original and new variants will continue to appear.

Preliminary research suggests that the first-generation of vaccines offer some protection against the new variants, helping to reduce severe disease and hospitalisation. However, they will probably become less effective over time as the virus mutates further and the immunity that people have gained, either through vaccination or natural infection, wanes.

In terms of a universal coronavirus vaccine, the ultimate question, Hatchett believes, is whether there are any weak spots that are conserved across coronaviruses as a viral family to which you can develop immune responses that effectively protect you.

The key issue in creating a universal vaccine is how broad a coverage the vaccine should offer. This was also pointed out to us by Andrew Ward at the Scripps Research Institute in California. As he put it:

Should it be SARS-CoV-2 and variants? Should it be SARS-1 and SARS-2? Should it be all sarbecocoviruses [a subgroup of SARS viruses of which SARS-CoV-1 and 2 are notable members] or SARS-like viruses? Thats unknown. We know that SARS viruses exist in bats and pangolins and theyve never been as big of a problem as now. But its one of those things, that if its not really a problem do we go after it and try to proactively get vaccine programmes deployed and get people either vaccinated or stockpile vaccines?

Creating a universal vaccine is itself highly challenging. For example, scientists have tried for years but not yet succeeded in developing a universal vaccine for flu. Nor have they yet managed to create one for HIV. In part, this is because the surface proteins found on these viruses frequently change their appearance. This makes it difficult for our immune system to recognise the virus.

But scientists have made enormous advances in recent years in understanding the interaction between the immune system and viruses that cause flu and HIV. They are now deploying this knowledge to build a universal vaccine for coronaviruses, which do not change as fast.

One of the reasons for optimism with a universal coronavirus vaccine is the successful development of the SARS-CoV-2 vaccine. Made in record time, the foundation for the vaccine was laid many years ago. Until the 1980s most vaccines were developed by modifying a virus or bacteria to make it no longer dangerous.This was achieved by weakening or inactivating the pathogen so that it could be injected safely to stimulate an immune response. While highly successful for protecting against a host diseases like measles, polio, rabies and chickenpox, this approach didnt prove effective in all diseases.

By the 1980s vaccine production stood on the cusp of change helped by the emergence of biotechnology. Where this was first successfully applied was in the development of a vaccine against hepatitis B, which is estimated to cause more deaths worldwide than TB, HIV or malaria.

The first hepatitis B vaccine was developed by Maurice Hilleman at Merck. Approved in 1981, it was the first vaccine to protect against cancer. Chronic hepatitis B is a major cause of liver cancer. In fact, it is second only to tobacco as a human carcinogen. What was novel about the hepatitis B vaccine was that instead of using the whole hepatitis B virus, which was difficult to grow in the laboratory, it used only a coat surface particle of the virus. This was a major breakthrough for vaccine technology.

Another vaccine that uses virus particles is the one against the human papillomavirus (HPV) which causes cervical cancer, a disease that globally kills 260,000 women every year. First licensed in 2005, the HPV vaccine took years to develop. It consists of tiny proteins that look like the outside of four types of real HPV produced in yeast.

Vaccine technology underwent a further revolution following the outbreak of the swine flu pandemic that swept the world for 19 months from January 2009. The pandemic killed between 151,700 and 575,400 people worldwide. Caused by an H1N1 influenza virus, the episode was an important reminder of the speed that pandemics can strike and the chaos they can sow. It was also a salutary lesson for companies who developed hundreds of millions of licensed vaccine doses to counter the pandemic. Although achieved within just six months, a historical record, this was not fast enough by then the peak of infections had passed.

Part of the delay was because of the time it took to grow enough of the virus in eggs or cultured mammalian cells. Another method, using genetic engineering to produce the virus, proved much faster, but was hampered by regulatory hurdles. Determined to accelerate vaccine availability for future pandemics, from 2011, vaccine experts put in place a new strategy that took advantage of advances in genomics and the open sharing of electronic sequence data. Coupled with a new ability to synthesise genes, these tools gave scientists the power to design genome segments from a virus to prepare vaccines to train the body to recognise and target a real virus if it invaded.

Critically, the new synthetic approach moved vaccine development away from the time-consuming process of isolating and shipping viruses between different sites and then growing them at scale. All that was needed was to download the relevant sequence data from the internet and synthesise the right genes to generate relevant viral components to start vaccine development. Speed was not the only advantage the new method offered. It also reduced any potential biohazard risks involved in manufacturing the vaccine.

Attention was also paid to making the testing process more efficient. Usually the slowest part of vaccine development, such testing often takes years to complete. Tests are first conducted in animals, to assess the safety, the strength of the immune response stimulated and protective efficacy of the vaccine candidate. Once this is done it is tested in humans.

Human trials are run in three phases, each with increasing numbers of people and escalating costs. One means to reduce the time needed and cut costs was to take advantage of new biomarkers. These provided a means to measure both normal and pathological processes as well as responses to a drug. Such biomarkers made it possible to determine the toxicity and efficacy of a candidate much earlier in the clinical trial process and to run multiple trials in parallel without compromising on safety.

In 2011, a group of scientists from the companies Novartis and Synthetic Genomics, as well as the Craig Venter Institute (a non-profit research organisation) proved they could develop a vaccine candidate in a matter of days.

Their approach was first successfully put to the test in March 2013 when Chinese health officials reported a novel strain of avian influenza had infected three people. Within just a week of gaining access to the viruss genome sequence, the Novartis team, headed by Rino Rappoli, managed to create a fully synthetic RNA-based vaccine ready for pre-clinical testing, which proved safe and elicited a good immune response.

Marking the switch from what Rappouli calls analogue vaccines to digital vaccines, the 2013 work provided a template for when COVID-19 was declared a pandemic on March 11, 2020. The first dose of the COVID-19 vaccine candidate, developed by Moderna, was ready for phase I testing in humans by March 16 2020. Many other vaccine candidates soon entered the pipeline thereafter.

What also helped propel the first COVID-19 vaccines forward was the explosion in knowledge about the atomic structure of proteins found on the surface of viruses and antibodies that bound to them. According to Ward this was greatly helped by advances in cryo-electron microscopy which as he says opened up the door for HIV and other pathogens. With the technique, Ward and his colleagues discovered that coronaviruses gained entry and fused with human cells with the help of a small loop of amino acids, called S-2P, on the top of their spike proteins. This laid an important foundation for creating the COVID-19 vaccines.

Another critical development was the discovery of broadly neutralising antibodies (bNAbs). First isolated in the early 1990s in the serum of people living with HIV-1, these antibodies only appear in some people after years of infection. Such antibodies have the advantage that they can neutralise multiple diverse strains of the virus in one stroke.

Finding the bNAbs critically opened up a new avenue for vaccine design. In particular, it offered the possibility of creating a universal vaccine against flu and also a vaccine for HIV which so far has been difficult to do because it mutates so fast. Several groups had already made progress in this field before COVID-19 struck, which they quickly turned towards coronaviruses. Their goal was to create a vaccine to stimulate the production of bNAbs targeting the receptor binding domain (RBD) located on the coronavirus spike protein.

One approach, outlined to us by Barton Haynes, an immunologist at Duke University, involves attaching little bits of the RBD, from multiple coronaviruses, to a protein nanoparticle for use as a vaccine candidate. Promisingly this was shown in monkeys to not only block SARS-CoV-2 and its new concerning variants but also SARS-CoV-1 and a group of bat coronaviruses which could spill over to humans in the future.

Another potential vaccine was described to us by Pamela Bjorkman, a structural immunologist at the Caltech. Her team developed it based on a virus particle platform first devised at Oxford University, in 2016. She said:

My lab really does structural biology, which means that we look at the 3D structures of the targets of the immune system, which are usually spikes that come out of the virus. So coronaviruses have the famous spikes, and so does HIV and flu.

One of the things weve been trying to do [for a vaccine] is to make a nanoparticle, which is a small, little thing that looks like a miniature soccer ball. And attach pieces of the spike to that using a very easy technology that was developed at Oxford University.

Their vaccine presents many different RBD fragments, from a variety of animal coronaviruses, grafted onto small proteins attached to a nanoparticle scaffolding. Tests in mice showed a single dose of the vaccine could neutralise multiple human and animal coronaviruses, including ones not included in the vaccine design.

According to our interview with Jonathan Heeney, a comparative pathologist at the the University of Cambridge, his group has also developed a promising broad coverage coronavirus vaccine. Based on detailed screening of the viruss structure they have synthesised DNA constructs to plug into conventional vaccine platforms and the latest mRNA vaccine technology.

The vector is specially designed not to trigger unintentional hyper-inflammatory responses, which can sometimes be life threatening. In animal studies, their candidate provided protection against a variety of sarbecoviruses, which cover SARS-CoV-1, SARS-CoV-2 and many bat coronaviruses.

All three outlined approaches have yet to be tested in humans. The Cambridge one is set to enter phase 1 trials in the autumn and the one at Duke University is nearing that milestone too. Both the Cambridge and Caltech candidates have the attraction that they can be produced as a heat-stable and freeze-dried powder. This will make their storage and distribution much easier than the current mRNA vaccines (Moderna and Pfizer). It will also make production much cheaper, which is vital to ensuring equitable access to the vaccine across the world and bringing the pandemic under control.

While scientists have the tools to develop a pan-coronavirus vaccine within a year, its creation would not be the end of the story. Growing population density, human mobility and ecological change means that the world will continue to face the threat of new pandemics.

Meeting this challenge will require a high degree of outbreak vigilance, political will and international cooperation as well as continued investment in vaccine development well beyond the end of the COVID-19 pandemic. As the WHO put it in September 2020, a global pandemic requires a world effort to end it - none of us will be safe until everyone is safe.

Access to vaccines is also only one arm of what is needed to combat pandemics. What SARS-CoV-2 has also taught us is the importance of rapid frontline genomic sequencing on the ground to swiftly detect newly emerging threats. As Hatchett argues, the key to radically reducing epidemic and pandemic risk to the world is through earlier detection, earlier sequencing, and earlier more tailored public health responses.

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COVID variants: we spoke to the experts designing a single vaccine to defeat them all - The Conversation UK

To solve the myriad challenges to the natural order that humankind has created over the years, Elizabeth Kolbert believes if there is to be an answer to the problem of control, its going to be more control.

In Under a White Sky: The Nature of the Future, Kolbert, a Pulitzer Prize-winning staff writer at The New Yorker, travels the world in search of crises we have created and are now fixing, however haltingly. Similarly, journalist Nathaniel Rich limns a portrait of ecological challenges in Second Nature: Scenes from a World Remade. Both authors apply sensitive, searching scrutiny to major and minor ecological issues and, through their reporting, attempt to forge a path forward for humanity to humbly but effectively overcome harms inflicted on the natural world.

Rich traverses the treacherous ground of human-created natural disasters, including the poisoning of groundwaters in West Virginia by a DuPont Teflon plant, the accidental venting of millions of cubic feet of natural gas from a Southern California Gas facility in northern Los Angeles, and the erosive effect on the Louisiana coastline of oil and gas extraction.

He also explores the hard work of individuals striving to use technology to help humans transcend our natural boundariesor, if you like, our human-created problemssuch as Nate Park, a product developer at Hampton Foods cultivating slaughter-free chickens and eggs. Then theres Auden Schendler, who leads sustainability efforts at the Aspen Skiing Company and forged an unlikely partnership with Bill Koch to capture methane from a coal mine and thereby power the entire resort, and Shin Kubota, a Japanese marine biologist whose jellyfish research seeks to turn back time and achieve nothing less than immortality.

Meanwhile, Kolbert dives deep into the water world along the southern American coastline. Every 90 minutes, Louisiana loses a football fields worth of land, and every few minutes, another tennis courts worth disappears. The levees, first built by the French in the early 18th century, have simultaneously saved and threatened New Orleans, flushing floodwaters away from populated areas into spillways that generate new hydrological problems.

This vast system, built to keep southern Louisiana dry, Kolbert observes, is the very reason the region is disintegrating, coming apart like an old shoe. Nevertheless, the states Coastal Protection and Restoration Authority has plowed ahead. It plans a $1.4 billion diversion project that will channel the mighty Mississippi into what amounts to a brand-new river that would rank as the twelfth largest in the United States, measured by waterflow.

Rich, who chronicles the fight against this master plan by the Save Louisiana Coalition of, fishermen and environmental activists, labels it an ecological monsterthe product of human engineering, compromise, brute force. In fact, the delta has become so heavily engineered hydrologists now refer to it as a coupled human and natural system.

Similarly, Rich, who lives in New Orleans, documents the citys halting recovery from the depredations of Katrina, particularly in the Lower Ninth Ward. He observes the invasion of the Lower Ninth by hitherto unseen species of flora and fauna in the wake of the hurricanes massive depopulation resembled something of a Frankensteins monster, a hybrid of human and natural components.

Mayor Mitch Landrieus ambitious Nuisance Lot Maintenance Pilot Program aimed to mow or otherwise clear vacant properties to deprive invasive species of a congenial habitat. But that effort faltered, as Chinese tallow trees, great egrets, falcons, and even alligators replaced their human predecessors.

The extinction and endangerment of species present another thorny challenge. One way to make sense of the biodiversity crisis, Kolbert muses, would simply be to accept it. The history of life has, after all, been punctuated by extinction events, both big and very, very big.

But while asteroid landings, volcanic eruptions, and other natural phenomena have terrorized and devastated species since time immemorial, humanity feels differently when we contribute to those extinctions. People are reluctant to be the asteroid, Kolbert notes. Instead, we seem to fancy becoming those who breathe life into Lazarus, not only preserving endangered species but even reviving extinct ones.

In a section entitled As Gods, Rich examines the de-extinction movement championed by Stewart Brand, the conservationist best known for inaugurating the Whole Earth Catalog (motto: We are as gods and might as well get good at it) decades ago. At a Harvard Medical School symposium called Bringing Back the Passenger Pigeon, Brands wife Ryan Phelan, a life sciences entrepreneur awed by a demonstration of genome-editing technology, noted that de-extinction went from concept to potential reality right before our eyes. Various teams are hard at work re-creating the California grizzly bear, the Tasmanian tiger, and the Carolina parakeet, among many other species.

Kolbert profiles the late Ruth Gates, a celebrated marine biologist whose lifes work entailed reinvigorating the population of wild coral through assisted evolution and other extraordinary means. Im a realist, Gates told Kolbert. I cannot continue to hope that our planet is not going to change radically. It already is changed. Her methods included raising coral in controlled, stressful environments and releasing them into the wild to forge sturdier, climate-resistant populations.

Our project, Gates proclaimed, is acknowledging that a future is coming where nature is no longer fully natural. Rich believes that moment has already arrived: What we still, in a flourish of misplaced nostalgia, call the natural world is gone, if ever it existed. Gatess colleague Madeleine Van Oppen regards assisted evolution as buying time or filling that gap, being a bridge between now and the day when were really holding down climate change or, hopefully, reversing it.

Similar lessons apply to genetic engineering, which weve been practicing for decades but appears in recent years to have taken a quantum leap with the advent of technologies like CRISPR. Kolbert details successful efforts to detoxify the cane toad, an invasive species wreaking havoc on Australian biodiversity. Mark Tizard, who led the project, sought to restore balance to an environment upended by the toad invasion.

The classic thing people say with molecular biology is: Are you playing God? he explained to Kolbert. Well, no. We are using our understanding of biological processes to see if we can benefit a system that is in trauma. Rich echoes this medical metaphor, noting that environmentalists have accepted that a threatened ecosystem requires steady interventive care, as might any patient in critical condition.

Yet with CRISPR we seem to be treading ever farther into no mans land. In a world of synthetic gene drives, Kolbert writes, the border between the human and the natural, between the laboratory and the wild, already deeply blurred, all but dissolves. As we play an increasingly intensive role in accelerating genetic change, not only do people determine the conditions under which evolution is taking place, people canagain, in principledetermine the outcome.

At the same time, arent technologies like CRISPR simply a technological advancement on techniques humans have employed for millennia to better our world? Ben Novak, a de-extinction researcher, told Rich that people grow up with this idea that the nature they see is natural, but theres been no real natural element to the earth the entire time human beings have been around.

How we think about hubris represents another challenge. On the one hand, its the height of arrogance to imagine that humanity, having intervened substantially in the natural order, can sit back and let it heal itself. Its just absolute hubris and so arrogant to think that we can survive without everything else, Paul Hardisty, the head of Australias National Sea Simulator, which strives ambitiously to nurture and harden the entire Great Barrier Reef, told Kolbert.

On the other hand, believing that we can solve every problem, including the ones we create, is no less conceited. Wasnt it just another kind of hubris, Kolbert wonders, to imagine all-of-reef-scale interventions? By the logic of immovable objects and unstoppable forces, wont we eventually create an environmental problem that we wont be able to solve?

Perhaps the clearest, and subtlest, articulation of appropriate balance comes from Brand, who noted that, contrary to humanitys attempts for thousands of years to batter nature into submission, we are now engaged in a whole different approach: more humble and more adroit. The skill were learning is how to nuance nature. Humility, nuance, and determination appear to be the sharpest tools in our small, but technologically advanced, kit.

Climate change represents another opportunity for scientific breakthroughs that arguably cast humans in the role of gods, and hopefully not in a Greek tragedy. With global temperatures on track for a 1.5-2-degree-Celsius rise in the coming decades, curbing carbon emissions seems to some to have become more urgent. With the worlds heaviest emitters in the developing world unlikely to take dramatic action, researchers have cast an increasingly wider net to ensnare more radical alternatives. Several competing teams have sought to capture carbon in the air, convert it to rock, and sequester it deep underground.

In the chapter from which her book takes its name, then, Kolbert explores the promising and terrifying field of solar geoengineering, an ambitious form of global tinkering premised on the idea of throw[ing] a gazillion reflective particles into the stratosphere, and less sunlight will reach the planet. White skies would supplant blue ones as tiny fragments of diamond, salt, or other minerals would absorb heat and lower global temperatures dramatically. The risks of agricultural damage and air pollution are significant, and we would be remaking the world in an unprecedented fashion, but we may soon have no alternative.

Harvards Dan Schrag, a prominent environmentalist, reckons that such engineering efforts may be the best chance of survival for most of the earths natural ecosystemsalthough perhaps they should no longer be called natural if such engineering systems are ever deployed. Indeed, we entered a hybrid natural-human world thousands of years ago, and the only way to preserve that world requires further, carefully calibrated interventions.

Both books would have benefitted from a reckoning with either (or both) religious philosophy and historical lessons about how humanity has interacted with our environment. But the contemporary vignettes that Kolbert and Rich sketch of a natural world confronting problems large and smalland the efforts humankind is making to ameliorate themspur reflection and, one hopes, a resolve on our part to steward our world with determination and humility.

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Environmentalists Argue That To Save The Planet, We Must Play God - The Federalist