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Delivery system can make RNA vaccines more powerful

Delivery system can make RNA vaccines more powerful

Vaccines made from RNA hold great potential as a way to treat cancer or prevent a variety of infectious diseases. Many biotech companies are now working on such vaccines, and a few have gone into clinical trials.

One of the challenges to creating RNA vaccines is making sure that the RNA gets into the right immune cells and produces enough of the encoded protein. Additionally, the vaccine must stimulate a strong enough response that the immune system can wipe out the relevant bacteria, viruses, or cancer cells when they are subsequently encountered.

MIT chemical engineers have now developed a new series of lipid nanoparticles to deliver such vaccines. They showed that the particles trigger efficient production of the protein encoded by the RNA, and they also behave like an “adjuvant,” further boosting the vaccine effectiveness. In a study of mice, they used this RNA vaccine to successfully inhibit the growth of melanoma tumors.

“One of the key discoveries of this paper is that you can build RNA delivery lipids that can also activate the immune system in important ways,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

Anderson is the senior author of the study, which appears in the Sept. 30 issue of Nature Biotechnology. The lead authors of the study are former postdocs Lei Miao and Linxian Li and former research associate Yuxuan Huang. Other MIT authors include Derfogail Delcassian, Jasdave Chahal, Jinsong Han, Yunhua Shi, Kaitlyn Sadtler, Wenting Gao, Jiaqi Lin, Joshua C. Doloff, and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute.

Vaccine boost

Most traditional vaccines are made from proteins produced by infectious microbes, or from weakened forms of the microbes themselves. In recent years, scientists have explored the idea of making vaccines using DNA that encodes microbial proteins. However, these vaccines, which have not been approved for use in humans, have so far failed to produce strong enough immune responses.

RNA is an attractive alternative to DNA in vaccines because unlike DNA, which has to reach the cell nucleus to become functional, RNA can be translated into protein as soon as it gets into the cell cytoplasm. It can also be adapted to target many different diseases.

“Another advantage of these vaccines is that we can quickly change the target disease,” he says. “We can make vaccines to different diseases very quickly just by tinkering with the RNA sequence.”

For an RNA vaccine to be effective, it needs to enter a type of immune cell called an antigen-presenting cell. These cells then produce the protein encoded by the vaccine and display it on their surfaces, attracting and activating T cells and other immune cells.

Anderson’s lab has previously developed lipid nanoparticles for delivering RNA and DNA for a variety of applications. These lipid particles form tiny droplets that protect RNA molecules and carry them to their destinations. The researchers’ usual approach is to generate libraries of hundreds or thousands of candidate particles with varying chemical features, then screen them for the ones that work the best.

“In one day, we can synthesize over 1,000 lipid materials with multiple different structures,” Miao says. “Once we had that very large library, we could screen the molecules and see which type of structures help RNA get delivered to the antigen-presenting cells.”

They discovered that nanoparticles with a certain chemical feature — a cyclic structure at one end of the particle — are able to turn on an immune signaling pathway called stimulator of interferon genes (STING). Once this pathway is activated, the cells produce interferon and other cytokines that provoke T cells to leap into action.

“Broad applications”

The researchers tested the particles in two different mouse models of melanoma. First, they used mice with tumors engineered to produce ovalbumin, a protein found in egg whites. The researchers designed an RNA vaccine to target ovalbumin, which is not normally found in tumors, and showed that the vaccine stopped tumor growth and significantly prolonged survival.

Then, the researchers created a vaccine that targets a protein naturally produced by melanoma tumors, known as Trp2. This vaccine also stimulated a strong immune response that slowed tumor growth and improved survival rates in the mice.

Anderson says he plans to pursue further development of RNA cancer vaccines as well as vaccines that target infectious diseases such as HIV, malaria, or Ebola.

“We think there could be broad applications for this,” he says. “A particularly exciting area to think about is diseases where there are currently no vaccines.”

Materials provided by Massachusetts Institute of Technology

DNA structure

New evidence of forces responsible for separation of DNA discovered

According to a piece of new evidence, the force which holds the DNA might also be responsible for change of shape so that its repair, gene shuffling and copying can take place. The iconic double helix structure of our DNA was discovered back in 1950. It has a structure similar to that of a twisted ladder in which the nitrogen base pairs in the middle are held by the hydrogen bonds. The findings appear in the Proceedings in the National Academy of Sciences. 

These bonds are considered as a “fundamental paradigm” because of their role in holding the DNA together. However, apart from this, one important consideration is that they are water-repelling or hydrophobic. 

Replication of DNA occurs with the help of many enzymes, in which DNA molecules are essentially unzipped by enzymes by the removal of hydrogen bonds. But this might not be the only way to do it. Scientists from the Chalmers University of Technology, Sweden have tested the DNA in an increased hydrophobic environment where they found that the water-repelling force can also be used for unraveling it. It loses its structure in a water-repelling environment when a solution of polyethylene glycol is added which is a semi-hydrophobic solution. 

Bobo Feng, lead author, and the chemical engineer said that the DNA is protected by the cells and not exposed to the hydrophobic environments that might have harmful molecules. But for its use, the DNA has to be opened up. It is kept in a water solution most of the time but the environment changes to a hydrophobic one when the DNA has to be edited, copied or repaired. 

Steven Brenner, a NASA molecular biophysicist said that although this is an important discovery of a new technique of melting the DNA for its repair, it has not been covered accurately by the media. The results do not suggest that hydrogen bonds are not important for the formation of DNA while the hydrophobic forces are. This is not a new idea as models considering hydrophobic interactions in the DNA date back to the 1990s. Researchers in 1997 tested the idea that only hydrogen bonds are sufficient to keep the double helix of DNA together. It was confirmed by a later study in 2004 that hydrogen bonding was not necessary for the stability of base pairs. A 2017 study revealed that cells are not affected by the lack of complementary hydrogen bonds as the synthetic bases are translated with the help of only hydrophobic forces. 

Floyd Romesberg, lead author of the 2017 study and a biochemist said that complementary hydrogen bonds might be considered the main definitions of DNA and RNA however there are other forces that can take part in the processes of information retrieval and storage. It often occurs that the biases of the chemist separating the molecules get reflected in the analysis of the model rather than the molecules themselves. Benner feels that self-explanations can convince us to understand what is happening if the models allow us to actually make things. 

Currently, both the concepts of hydrogen-bonding and hydrophobicity help us to make advances in human medicine besides powering NASA’s search for extraterrestrial organisms. 

Feng said that it was not surprising that this behavior was not identified to date as DNA was never placed in a hydrophobic environment. 

Journal Reference:  PNAS  (Proceedings of the National Academy of Sciences of the United States of America)

Skeletons in Roopkund Lake

DNA analysis of the Roopkund skeletons makes its mystery even more complex

Roopkund lake amidst the Himalayan mountains has been a place of mystery. It is a shallow lake which is filled with the bones of human beings, due to which it is also known as Skeleton Lake and the reason behind the presence of skeletons is not yet known. 

One hypothesis is that a large number of people died due to a single catastrophe. However, this idea is now challenged by DNA analysis of 38 skeletons present there. It reveals that different groups of people from distant places such as the Mediterranean came to the lake over a period of 1000 years. The paper appears in the journal Nature Communications

David Reich, a geneticist from Harvard Medical School said that biomolecular analysis including radiocarbon dating and stable isotope dietary reconstruction reveals the history of the lake to be more complex than imagined. Geneticist Kumarasamy Thangaraj, CSIR Centre for Cellular and Molecular Biology sequenced mitochondrial DNA of 72 skeletons a decade ago. Some skeletons had DNA of a local Indian origin however several appeared to have come from West Eurasia. This led to a deeper analysis of genome sequencing in which genome-wide DNA was produced for 38 persons. These were compared against 1521 ancient and 7985 current persons from all over the world. 23 persons had similar DNA to that of people from India however 14 persons had similar DNA to that of residents in current Greece and Crete. And one person had DNA from Southeast Asian origin. 

Eadaoin Harney, Harvard University said that scientists are highly surprised by this variation in the genetics of the skeletons. That the DNAs of the skeletons reveal similarities with the eastern Mediterranean suggests that the Lake attracted visitors from all over the world. Isotope analysis supports these findings. Some stable isotopes can be absorbed in plants which are then eaten by people. These replace some calcium in bones and teeth which can be matched suitably to specific locations. 

Ayushi Nayak, archaeologist of Max Planck Institute for Science of Human History said that persons with Indian origins had a diet mainly depending on C3 and C4 derived food sources. It is consistent with the genetic evidence that they belonged to several socioeconomic groups in South Asia. However, people connected to the eastern Mediterranean had a diet with a lesser amount of millet. 

What is even more mind-boggling is the time of arrival of these groups. Radiocarbon dating estimates that the bones related to Indian ancestry came between the 7th and 10th centuries and those from the Mediterranean and Southeast Asia were dated between the 17th and 20th centuries. It is very much possible that skeletons not tested could belong to other regions from different time periods.

We still do not know how these persons came to the Lake and what is the cause of their death. Scientists have to dig deeper to find the answers. 

Journal Reference: Nature Communications

Study furthers radically new view of gene control

Study furthers radically new view of gene control

In recent years, MIT scientists have developed a new model for how key genes are controlled that suggests the cellular machinery that transcribes DNA into RNA forms specialized droplets called condensates. These droplets occur only at certain sites on the genome, helping to determine which genes are expressed in different types of cells.

In a new study that supports that model, researchers at MIT and the Whitehead Institute for Biomedical Research have discovered physical interactions between proteins and with DNA that help explain why these droplets, which stimulate the transcription of nearby genes, tend to cluster along specific stretches of DNA known as super-enhancers. These enhancer regions do not encode proteins but instead, regulate other genes.

“This study provides a fundamentally important new approach to deciphering how the ‘dark matter’ in our genome functions in gene control,” says Richard Young, an MIT professor of biology and member of the Whitehead Institute.

Young is one of the senior authors of the paper, along with Phillip Sharp, an MIT Institute Professor and member of MIT’s Koch Institute for Integrative Cancer Research; and Arup K. Chakraborty, the Robert T. Haslam Professor in Chemical Engineering, a professor of physics and chemistry, and a member of MIT’s Institute for Medical Engineering and Science and the Ragon Institute of MGH, MIT, and Harvard.

Graduate student Krishna Shrinivas and postdoc Benjamin Sabari are the lead authors of the paper, which appears in Molecular Cell on Aug. 8.

“A biochemical factory”

Every cell in an organism has an identical genome, but cells such as neurons or heart cells express different subsets of those genes, allowing them to carry out their specialized functions. Previous research has shown that many of these genes are located near super enhancers, which bind to proteins called transcription factors that stimulate the copying of nearby genes into RNA.

About three years ago, Sharp, Young, and Chakraborty joined forces to try to model the interactions that occur at enhancers. In a 2017 Cell paper, based on computational studies, they hypothesized that in these regions, transcription factors form droplets called phase-separated condensates. Similar to droplets of oil suspended in salad dressing, these condensates are collections of molecules that form distinct cellular compartments but have no membrane separating them from the rest of the cell.

In a 2018 Science paper, the researchers showed that these dynamic droplets do form at super enhancer locations. Made of clusters of transcription factors and other molecules, these droplets attract enzymes such as RNA polymerases that are needed to copy DNA into messenger RNA, keeping gene transcription active at specific sites.

“We had demonstrated that the transcription machinery forms liquid-like droplets at certain regulatory regions on our genome, however we didn’t fully understand how or why these dewdrops of biological molecules only seemed to condense around specific points on our genome,” Shrinivas says.

As one possible explanation for that site specificity, the research team hypothesized that weak interactions between intrinsically disordered regions of transcription factors and other transcriptional molecules, along with specific interactions between transcription factors and particular DNA elements, might determine whether a condensate forms at a particular stretch of DNA. Biologists have traditionally focused on “lock-and-key” style interactions between rigidly structured protein segments to explain most cellular processes, but more recent evidence suggests that weak interactions between floppy protein regions also play an important role in cell activities.

In this study, computational modeling and experimentation revealed that the cumulative force of these weak interactions conspire together with transcription factor-DNA interactions to determine whether a condensate of transcription factors will form at a particular site on the genome. Different cell types produce different transcription factors, which bind to different enhancers. When many transcription factors cluster around the same enhancers, weak interactions between the proteins are more likely to occur. Once a critical threshold concentration is reached, condensates form.

“Creating these local high concentrations within the crowded environment of the cell enables the right material to be in the right place at the right time to carry out the multiple steps required to activate a gene,” Sabari says. “Our current study begins to tease apart how certain regions of the genome are capable of pulling off this trick.”

These droplets form on a timescale of seconds to minutes, and they blink in and out of existence depending on a cell’s needs.

“It’s an on-demand biochemical factory that cells can form and dissolve, as and when they need it,” Chakraborty says. “When certain signals happen at the right locus on a gene, the condensates form, which concentrates all of the transcription molecules. Transcription happens, and when the cells are done with that task, they get rid of them.”

A new view

Weak cooperative interactions between proteins may also play an important role in evolution, the researchers proposed in a 2018 Proceedings of the National Academy of Sciences paper. The sequences of intrinsically disordered regions of transcription factors need to change only a little to evolve new types of specific functionality. In contrast, evolving new specific functions via “lock-and-key” interactions requires much more significant changes.

“If you think about how biological systems have evolved, they have been able to respond to different conditions without creating new genes. We don’t have any more genes that a fruit fly, yet we’re much more complex in many of our functions,” Sharp says. “The incremental expanding and contracting of these intrinsically disordered domains could explain a large part of how that evolution happens.”

Similar condensates appear to play a variety of other roles in biological systems, offering a new way to look at how the interior of a cell is organized. Instead of floating through the cytoplasm and randomly bumping into other molecules, proteins involved in processes such as relaying molecular signals may transiently form droplets that help them interact with the right partners.

“This is a very exciting turn in the field of cell biology,” Sharp says. “It is a whole new way of looking at biological systems that is richer and more meaningful.”

Some of the MIT researchers, led by Young, have helped form a company called Dewpoint Therapeutics to develop potential treatments for a wide variety of diseases by exploiting cellular condensates. There is emerging evidence that cancer cells use condensates to control sets of genes that promote cancer, and condensates have also been linked to neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Huntington’s disease.

Materials provided by Massachusetts Institute of Technology

gene editing artist

Chinese scientists create safer alternative to CRISPR which avoids ethical concerns

A team of Chinese researchers have created an efficient and very safe technology for editing RNA that could avoid the side effects to a great extent and also the ethical concerns which came from the previous technologies of gene-editing. The study has been published in the journal Nature Biotechnology

This feat comes after half a year when Chinese researcher He Jiankui claimed that he had made the world’s first gene-edited twins who are immune to HIV. This announcement caused a whirlwind of condemnation all over the world. Many Chinese and international researchers condemned it as any application of gene editing was unethical if used on human embryos for reproductive purposes. He used the technology of CRISPR-Cas9, that was adapted from a genome editing system which occurred naturally in bacteria. The Cas9 enzyme, a protein that plays a very important role in the immunological defence of specific bacteria against the DNA viruses would be introduced for cutting the DNA of the viruses in the human body. 

Wei Wensheng, a leading researcher of the technology and also a biologist at the Peking University said that this technology essentially depends on the delivery of chemically modified guide RNAs or exogenous proteins that may lead to a delivery barrier.

Zhou Zhuo, another research team member said that on the contrary, the latest technology known as Leveraging Endogenous ADAR for Programmable Editing of RNA or LEAPER uses the native proteins and hence does not alter the DNA in a direct manner. Because of these factors, it would not bring any heritable changes and is safe. It uses engineered RNA’s for recruiting native enzymes to change certain adenosine to inosine. Zhou also stated that experiments conducted at a cellular level in the last two years showed that LEAPER is capable of achieving editing efficiencies up to 80 percent. He further mentioned that the team is now conducting tests on rats. Hence we have to wait to understand if it is suitable for use in human beings.

LEAPER is active in a very broad spectrum of cell types which includes several human primary cell types. It can also restore the deficient cells of patients having Hurler syndrome without evoking any kind of innate immune responses. Being a single-molecule system, LEAPER ensures highly precise and efficient RNA editing with large scale applications for basic research and therapy. 

Journal Reference: Nature Biotechnology

DNA methylation

Scientists capture DNA replication machinery at atomic resolution

Unwinding of double-stranded DNA and separating them into single strands which can be copied for cell division is an important aspect of how life works. A team of researchers at the Research Hospital of St. Jude Children’s have determined at the atomic resolution the actual structure of the machinery through which the process is driven. The study has been published in the Nature Communications journal.

According to the senior researcher of the study who termed it as one of the greatest mysteries existing in biology that how a double-stranded DNA separates to form single strands for initiating the replication process, this technique may help in figuring out how the mechanism works. Eric Enemark, Ph.D. and also an associate member of Structural Biology Department of St. Jude said that based on the crystal structure in the research, they have proposed a rotary mechanism which drives the transformation for initiating the DNA replication.

Before the process of cell division starts, the DNA must be copied in a precise manner in a method known as replication. This research focused on an enzyme that is ring-shaped and known as the minichromosome maintenance or MCM complex which plays an important role. During the process of DNA replication, the MCM complex is at the fork where the separation of the double-stranded DNA occurs to form single strands. After this, the strands are then copied for producing a new DNA molecule.

Enemark and his colleagues have created the first atomic resolution image in which the MCM complex is bound to the single-strand DNA and the other molecules which fuel the process of replication.

The image captured the important details which include the orientation of the MCM complex and the single-strand DNA. The elements depicted how the process actually works similar to a pulley system for pulling a single strand of DNA through the MCM complex following the unwinding of the DNA. Enemark said that the same mechanism can also explain how the process of DNA replication starts. Before cell division takes place, the double-stranded DNA is encircled by two separate complex enzymes of MCM.

On the basis of the new structure determined by the replication machinery, scientists have proposed that MCM complexes start to move in different directions which leads to the separation of double-stranded DNA to form single-stranded ones. He added that this particular event is the main component of cell division and it presents the essence of life in the most streamlined manner.

Research Paper: https://www.nature.com/articles/s41467-019-11074-3

Purple sea urchin

New research shows why Noah’s ark would not work

A first of a kind study has illuminated that marine species will survive even though in a world where the temperatures are rising and acidity is increasing in the water.

Melissa Pespeni a biologist at the University of Vermont who led the new research has said that moderately sized remnants may have little chance to persist on a climate-changed planet. She led a research which studied the larvae for experiments where the water was made acidic and alkaline. The study has been published in the Proceedings of the Royal Society B journal.

Small minorities of urchins were studied and surprisingly they found out a rare variation in DNA which was essential for their survival. When the water was made acidic the variants increased the frequency in water and let the next generation to choose how the proteins function like the shells which are hard but can be easily dissolved to manage the acidity in the cells. Along with these other needed genetic variation helped them survive in acidic conditions or a range of acid levels. The bigger the population, greater is the variation in the species. If we have a smaller population there are lesser chances of having a genetic variation.

Some organisms have the potential to survive the change due to change in physiology and due to the ability of migration but for many others, their only hope lies in evolution and potential changes in their DNA. The purple sea urchins which stretch from the reefs from California to Alaska are a snack for the otters. Due to the huge number of urchins and the wide expanse of the geographical area, urchins are likely survivors of the harsh future of rising temperatures and acidified oceans. The UVM team has written that the genetic mechanisms that allow rapid adaptation to extreme climatic conditions have been rarely explored.

A single generation experiment was started with 25 urchins caught from the wild. Each female of those 25 produced close to 200,000 eggs each out of which 20,000 survived, the DNA samples of this pool was taken for study and research. This large gene pool gave scientists the idea that the urchins could survive in acidic conditions. They can survive these slight changes in pH and can continue to protect them as long as they keep their population large. Discoveries of facts like these have long term implications on their survival and continuity of their species.

The two 31,000-year-old milk teeth

DNA from 31,000-year-old milk teeth leads to discovery of new group of ancient Siberians

The finding was part of a wider study which also discovered 10,000-year-old human remains in another site in Siberia are genetically related to Native Americans – the first time such close genetic links have been discovered outside of the US.

This individual is the missing link of Native American ancestry

Eske Willerslev

The international team of scientists, led by Professor Eske Willerslev who holds positions at St John’s College, University of Cambridge, and is director of The Lundbeck Foundation Centre for GeoGenetics at the University of Copenhagen, have named the new people group the ‘Ancient North Siberians’ and described their existence as ‘a significant part of human history’.

The DNA was recovered from the only human remains discovered from the era – two tiny milk teeth – that were found in a large archaeological site found in Russia near the Yana River. The site, known as Yana Rhinoceros Horn Site (RHS), was found in 2001 and features more than 2,500 artefacts of animal bones and ivory along with stone tools and evidence of human habitation.

The discovery is published as part of a wider study in Nature and shows the Ancient North Siberians endured extreme conditions in the region 31,000 years ago and survived by hunting woolly mammoths, woolly rhinoceroses, and bison.

Professor Willerslev said: “These people were a significant part of human history, they diversified almost at the same time as the ancestors of modern-day Asians and Europeans and it’s likely that at one point they occupied large regions of the northern hemisphere.”

Dr Martin Sikora, of The Lundbeck Foundation Centre for GeoGenetics and first author of the study, added: “They adapted to extreme environments very quickly, and were highly mobile. These findings have changed a lot of what we thought we knew about the population history of northeastern Siberia but also what we know about the history of human migration as a whole.”

Researchers estimate that the population numbers at the site would have been around 40 people with a wider population of around 500. Genetic analysis of the milk teeth revealed the two individuals sequenced showed no evidence of inbreeding which was occurring in the declining Neanderthal populations at the time.

The complex population dynamics during this period and genetic comparisons to other people groups, both ancient and recent, are documented as part of the wider study which analysed 34 samples of human genomes found in ancient archaeological sites across northern Siberia and central Russia.

Professor Laurent Excoffier from the University of Bern, Switzerland, said: “Remarkably, the Ancient North Siberians people are more closely related to Europeans than Asians and seem to have migrated all the way from Western Eurasia soon after the divergence between Europeans and Asians.”

Scientists found the Ancient North Siberians generated the mosaic genetic make-up of contemporary people who inhabit a vast area across northern Eurasia and the Americas – providing the ‘missing link’ of understanding the genetics of Native American ancestry.

It is widely accepted that humans first made their way to the Americas from Siberia into Alaska via a land bridge spanning the Bering Strait which was submerged at the end of the last Ice Age. The researchers were able to pinpoint some of these ancestors as Asian people groups who mixed with the Ancient North Siberians.

Professor David Meltzer, Southern Methodist University, Dallas, one of the paper’s authors, explained: “We gained important insight into population isolation and admixture that took place during the depths of the Last Glacial Maximum – the coldest and harshest time of the Ice Age – and ultimately the ancestry of the peoples who would emerge from that time as the ancestors of the indigenous people of the Americas.”

This discovery was based on the DNA analysis of a 10,000-year-old male remains found at a site near the Kolyma River in Siberia. The individual derives his ancestry from a mixture of Ancient North Siberian DNA and East Asian DNA, which is very similar to that found in Native Americans. It is the first time human remains this closely related to the Native American populations have been discovered outside of the US.

Professor Willerslev added: “The remains are genetically very close to the ancestors of Paleo-Siberian speakers and close to the ancestors of Native Americans. It is an important piece in the puzzle of understanding the ancestry of Native Americans as you can see the Kolyma signature in the Native Americans and Paleo-Siberians. This individual is the missing link of Native American ancestry.”

Materials provided by University of Cambridge

E coli with synthetic DNA

Scientists successfully create first living organism with synthetic DNA

By the earnest effort of scientists, the world’s first ever living organism with completely synthetic DNA has been created. The ambitious project finally proved that life can exist in certain controlled conditions. This can be used to make drugs such as insulin for diabetes and other medical compounds for multiple sclerosis, heart attacks and eye diseases.

Since the inception of heredity and evolution, life on earth shares a common code of resemblance that’s called DNA. The four nucleic acid letters of adenine, cytosine, guanine and thymine– or A, C, G and T can be strung into 64 combinations of 3 letters called codons.

Nearly, in all life forms from jellyfish to humans, there are 64 codons. But many of them do the same job. In total, 20 amino acids which are natural are synthesised by 61 codons, which can be binded together like a necklace. Three more codons are in effect stop signs. They inform the cell when the protein is done like a full stop mark marking the ending of a sentence.

The Laboratory of Molecular Biology of Medical Research Council in Cambridge, read and redesigned the DNA of the bacterium E.Coli. Experts were in a fix whether it would be possible or not. The Cambridge team worked hard to redesign the E.coli genome by going through its DNA while working on a computer. Scientists made a whopping 18000 edits to the DNA, stitched the whole DNA together and exchanged it with the original DNA of the bacteria. The result was a microbe with a completely synthetic and radically altered DNA code known as SYN61. The bug was showing unusual characteristics such as a little longer than normal while showing slower growth.

This edited variation SYN61 isn’t quite a red alert for its ancestors as the cells were a touch longer and were virus resistant. Now, it can be thought that how it would act as a resistance to a virus. The answer is simple, as their DNA is different, invading viruses will struggle to spread inside them making them virus resistant.

Efforts were made earlier too like the bug Mycoplasma Mycoides but it has smaller genome than E Coli and was also not redesigned. But as “records are made to be broken” and in that sense, other researchers are persistently working on bacterial genomes with more coding changes.

Finally, scientists have taken the field of synthetic genomes to a new level by building the largest ever synthetic genome to date. It is a landmark step of completely novel life form. The invention of this remarkable life will be a milestone in the history of heredity and evolution.

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DNA molecule depiction

Scientists create dynamic “living” object which has its own metabolism

Scientists at Cornell University have artificially synthesised a material which possesses three main traits of life namely metabolism, organisation and self-assembly. Such a task was possible as the researchers used the DNA so as to prepare machines which had the properties of living beings. The report has been published in the Science Robotics.

The technique which they used is named as DASH which stands for “DNA-based Assembly and Synthesis of Hierarchical” objects. The scientists prepared a DNA material which has the metabolism ability i.e the specific set of chemical processes which converts the food to the energy which is needed for sustaining life.

The three most important purposes of metabolism are generating energy from food for different cellular activities, converting food to the basic elements for proteins, nucleic acids, carbohydrates and removing several wastes such as nitrogenous wastes. Metabolic reactions are classified to two types, catabolic and anabolic.

However, scientists did not intend to create a living entity. They wanted to build a machine which has the functions of living beings. Professor Dan Luo, Department of Biological and Environmental Engineering mentioned that they are not preparing a different life but materials which are more lifelike than ever seen.

For any organism which is alive, there must be ways to coordinate the changes which take place continuously. Activities such as generation of new cells, removing the worn out ones, biodegradation are the key processes which are needed to maintain the form.

The most innovative aspect here is that the process of metabolism has been programmed and coded inside the DNA. It contains instructions for autonomous regeneration which then allows the object to grow on its own. Scientists have described metabolism in the paper as a method where the elements which make life are manufactured, synthesized, broken down and decomposed independently in a hierarchical way using biological processes.

With the help of the DASH method, the engineers manufactured a material which can independently emerge from its building blocks and arrange on its own. With the help of a 55 nucleotide base sequence, the molecules of DNA were multiplied several thousand times, and the DNA chains were created which were a few millimeters in size. After that, it was injected in a microfluidic device which provided energy in liquid flow and the building blocks for biosynthesis were made.

DNA prepared its new strands where the front end and the tail end were maintained in a suitable manner. Though the designs are primitive, this is a new possibility of making dynamic objects from biomolecules. Scientists are now working on ways so that the object can identify different stimuli and also seek for food when needed.